96 results on '"organ perfusion"'
Search Results
2. The impact and relevance of techniques and fluids on lung injury in machine perfusion of lungs
- Author
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Florian Ponholzer, Julia Dumfarth, Christoph Krapf, Andreas Pircher, Theresa Hautz, Dominik Wolf, Florian Augustin, and Stefan Schneeberger
- Subjects
EVLP ,PGD ,ex vivo ,organ perfusion ,transplantation ,techniques ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated. The variables relate to the engineering and function of the respective perfusion devices, such as the type of pump used, functional, like ventilation modes or physiological (e.g. perfusion solutions). This review reflects on the individual technical and fluid components relevant to EVLP and their respective impact on inflammatory response and outcome. We discuss key components of EVLP protocols and options for further improvement of EVLP in regard to PGD. This review offers an overview of available options for centers establishing an EVLP program and for researchers looking for ways to adapt existing protocols.
- Published
- 2024
- Full Text
- View/download PDF
3. NRP vs DHOPE vs COR-NMP in ECD-DCD Donation
- Author
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University Medical Center Groningen, Leiden University Medical Center, and Jeroen de Jonge, Principal Investigator, head of liver perfusion programme
- Published
- 2022
4. Trends and Obstacles to Implement Dynamic Perfusion Concepts for Clinical Liver Transplantation: Results from a Global Web-Based Survey.
- Author
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Parente, Alessandro, Flores Carvalho, Mauricio, Panconesi, Rebecca, Boteon, Yuri L., De Carlis, Riccardo, Dutkowski, Philipp, Muiesan, Paolo, Dondossola, Daniele, and Schlegel, Andrea
- Subjects
- *
LIVER transplantation , *INTERNET surveys , *PERFUSION , *UNIVERSITY hospitals ,WESTERN countries - Abstract
Background: Organ perfusion technology is increasingly used in many countries, with a focus, however, on the Western world. This study investigates the current international trends and obstacles to the broader routine implementation of dynamic perfusion concepts in liver transplantation. Methods: A web-based anonymous survey was launched in 2021. Experts of all involved specializations from 70 centers in 34 countries were contacted, based on the published literature and experience in the field of abdominal organ perfusion. Results: Overall, 143 participants from 23 countries completed the survey. Most respondents were male (67.8%) and transplant surgeons (64.3%) working at university hospitals (67.9%). The majority had experience with organ perfusion (82%), applying mainly hypothermic machine perfusion (HMP; 38%) and other concepts. While most (94.4%) expect a higher utilization of marginal organs with machine perfusion, the majority considers HMP the best technique to reduce liver discard-rates. While most respondents (90%) believed machine perfusion should be fully commissioned, the lack of funding (34%) and knowledge (16%) as well as limited staff (19%) were the three main obstacles to a routine clinical implementation. Conclusion: Although dynamic preservation concepts are increasingly used in clinical practice, significant challenges remain. Specific financial pathways, uniform regulations, and tight collaborations among involved experts are needed to achieve wider global clinical use. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. Editorial: Recent advances on renoprotection and kidney regeneration.
- Author
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Gimenez, Ignacio, Hugo, Christian, and Todorov, Vladimir T.
- Subjects
DIABETIC nephropathies ,KIDNEYS ,REGENERATION (Biology) ,BIOPRINTING ,KIDNEY tubules ,FIBROBLAST growth factors - Published
- 2023
- Full Text
- View/download PDF
6. Cardiovascular Activity of Ginkgo biloba—An Insight from Healthy Subjects.
- Author
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Silva, Henrique and Martins, Filipe Gazalho
- Subjects
- *
GINKGO , *BLOOD pressure , *HEART beat , *HEMODYNAMICS , *THERAPEUTICS , *CARDIOVASCULAR diseases - Abstract
Simple Summary: Ginkgo biloba is the oldest living tree species in the world and its extracts are among the most used herbal preparations in the prevention and treatment of cardiovascular diseases. Most clinical data on the efficacy of Ginkgo biloba is from clinical studies, with few results from healthy subjects. This paper provides a comprehensive review of the mechanisms underlying the known beneficial cardiovascular activities of Ginkgo biloba and its main compounds. This plant displays myocardial suppressant and vasorelaxant activities ex vivo. It improves perfusion in different vascular beds without significantly affecting blood pressure and heart rate. In addition, it displays an acceptable safety profile, with most reported adverse reactions constituting rare occurrences. Collectively, Ginkgo biloba impacts cardiovascular physiology, improving hemodynamics and organ perfusion. In the future, better controlled clinical studies should be performed in order to identify the target populations who could benefit the most with pharmacotherapeutic interventions involving this plant. Ginkgo biloba is the oldest living tree species in the world. Despite less than encouraging clinical results, extracts from its leaves are among the most used herbal preparations in the prevention and treatment of cardiovascular diseases. Most data on the efficacy of Ginkgo biloba on cardiovascular disease is from clinical studies, with few results from healthy subjects. This paper aims to provide a comprehensive review of the mechanisms underlying the known beneficial cardiovascular activities of Ginkgo biloba. It displays myocardial suppressant and vasorelaxant activities ex vivo, potentiating endothelial-dependent and -independent pathways. It improves perfusion in different vascular beds, namely ocular, cochlear, cutaneous, cerebral, and coronary. Although scarce, evidence suggests that Ginkgo biloba displays a heterogeneous effect on tissue perfusion which is dependent on the individual elimination pathways. It displays an acceptable safety profile, with most reported adverse reactions constituting rare occurrences. Collectively, Ginkgo biloba positively impacts cardiovascular physiology, improving hemodynamics and organ perfusion. In the future, better controlled clinical studies should be performed in order to identify the target populations who may benefit the most from pharmacotherapeutic interventions involving Ginkgo biloba. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Editorial: Recent advances on renoprotection and kidney regeneration
- Author
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Ignacio Gimenez, Christian Hugo, and Vladimir T. Todorov
- Subjects
kidney damage ,renal regeneration ,kidney imaging ,diagnostic markers ,organ perfusion ,ex vivo models ,Physiology ,QP1-981 - Published
- 2023
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- View/download PDF
8. Differential Cytokine Levels during Normothermic Kidney Perfusion with Whole Blood- or Red Blood Cell-Based Perfusates—Results of a Scoping Review and Experimental Study.
- Author
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De Beule, Julie, Keppens, Delphine, Korf, Hannelie, and Jochmans, Ina
- Subjects
- *
PERFUSION , *KIDNEYS , *ERYTHROCYTES , *CYTOKINES - Abstract
The ideal composition of the perfusate for normothermic kidney perfusion is unknown, though the perfusate commonly used to perfuse human kidneys contains leukocyte-depleted packed red blood cells (RBC), as this is believed to prevent excessive inflammation. We performed a systematic search identifying 19 articles reporting on cytokine levels during normothermic pig or human kidney perfusion. Cytokine levels varied widely across the reported studies. No direct comparisons of perfusate cytokines during perfusion with RBC or whole blood were performed, and no data on how these levels are influenced by ischemia are available. Therefore, we compared perfusate IL-6, IL-1β, TNF-α, TGF-β, IL-10, IL-8, and CCL2 levels during 4 h normothermic pig kidney perfusion with a whole blood- or RBC-based perfusate. Kidneys were exposed to either 1 h of warm or 22 h of cold ischemia. We found no evidence of different perfusate cytokine or gene expression levels in whole blood or RBC perfusions. There was no clear evidence to suggest that cytokine concentrations differ between ischemically injured kidneys and controls. In conclusion, pro-inflammatory and anti-inflammatory cytokines and chemokines are detectable in the perfusate and urine of kidneys undergoing normothermic perfusion. It is unclear how cytokine levels change in different ischemic conditions and whether the use of a leukocyte filter plays a role. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
9. Polycompartment Syndrome
- Author
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Minini, Andrea, Emara, Moataz M., Malbrain, Manu L. N. G., Coccolini, Federico, Series Editor, Coimbra, Raul, Series Editor, Kirkpatrick, Andrew W., Series Editor, Di Saverio, Salomone, Series Editor, Ansaloni, Luca, Editorial Board Member, Balogh, Zsolt, Editorial Board Member, Biffl, Walt, Editorial Board Member, Catena, Fausto, Editorial Board Member, Davis, Kimberly, Editorial Board Member, Ferrada, Paula, Editorial Board Member, Fraga, Gustavo, Editorial Board Member, Ivatury, Rao, Editorial Board Member, Kluger, Yoram, Editorial Board Member, Leppaniemi, Ari, Editorial Board Member, Maier, Ron, Editorial Board Member, Moore, Ernest E., Editorial Board Member, Napolitano, Lena, Editorial Board Member, Peitzman, Andrew, Editorial Board Member, Reilly, Patrick, Editorial Board Member, Rizoli, Sandro, Editorial Board Member, Sakakushev, Boris, Editorial Board Member, Sartelli, Massimo, Editorial Board Member, Scalea, Thomas, Editorial Board Member, Spain, David, Editorial Board Member, Stahel, Philip, Editorial Board Member, Sugrue, Michael, Editorial Board Member, Velmahos, George, Editorial Board Member, Weber, Dieter, Editorial Board Member, Malbrain, Manu L.N.G., editor, Kirkpatrick, Andrew W, editor, and Gamberini, Emiliano, editor
- Published
- 2021
- Full Text
- View/download PDF
10. The involvement of the NLRP3 inflammasome in donor lung injury
- Author
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Major, Triin, Yonan, Nizar, Fildes, James, and MacDonald, Andrew
- Subjects
617.5 ,evlp ,ex vivo lung perfusion ,IL-1B ,lung injury ,nlrp3 inflammasome ,pro-IL-1B ,organ perfusion ,lung transplantation ,inflammasome - Abstract
Lung transplantation remains the only feasible treatment option for people with end-stage pulmonary disease who do not respond to other therapeutic strategies. However, the demand for donor lungs greatly outweighs the availability of organ supply, which results in waiting list mortality. Lungs are extremely susceptible to damage within the donor environment, and only 20% of donor lungs meet the criteria for standard transplantation. This has led to increased use of marginal donor lungs, which in turn increases the risk of complications such as rejection and primary graft dysfunction. Ex vivo lung perfusion (EVLP) is used to evaluate, and also to improve pulmonary function in these marginal donor lungs. Interleukin-1B (IL-1B), a potent pro-inflammatory cytokine has been identified as a prognostic indicator of non-recovery in human EVLPs. The release of IL-1B is dependent on the assembly of inflammasome, a large multiprotein complex. The hypothesis of these studies was that inhibiting the NLRP3 inflammasome formation would reduce the release of active IL-1B thereby decreasing the inflammatory response during EVLP, thus potentially encouraging organ recovery. NLRP3 inflammasome inhibitor was introduced into porcine ex vivo organ perfusion systems of healthy lungs and damaged kidneys. Organ function was assessed along with the inflammatory profile of the organs in the control and treatment groups. Furthermore, the levels of other inflammasome-related inflammatory mediators IL-1B, pro-IL-1B, caspase-1 and IL-18 were measured in human EVLP perfusate and bronchoalveolar lavage samples from lungs that were transplanted and lungs that were discarded. Lastly, the concentrations of these mediators were assessed in plasma samples of lung transplant recipients immediately before and up to 72 hours post-operatively, and correlated the values with pulmonary oxygenation capacity as an indicator of lung function. Whilst a decrease in the extracellular inflammasome particles in the porcine ex vivo perfusions occurred, there were no differences between the control and the inhibitor groups in terms of their cytokine profiles, cellular outflow or organ function. This demonstrated that despite the inhibitor therapy reducing inflammasome activity, it did not convey protection or promote organ recovery. In the perfusate of human lungs that did not recondition during EVLP and were rejected for transplant, a significant increase in pro-IL-1B, the inactive precursor molecule expressed intracellularly, was detected. This suggests that inflammasome inhibition therapy alone may not protect donor lungs from injury or promote recovery, and that pro-IL-1B is released following cell death rather than actively secreted as part of a specific inflammatory process.
- Published
- 2018
11. Heart transplant advances: Ex vivo organ-preservation systemsCentral Message
- Author
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Benjamin S. Bryner, MD, Jacob N. Schroder, MD, and Carmelo A. Milano, MD
- Subjects
heart transplantation ,ex vivo heart perfusion ,organ perfusion ,organ recovery ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 ,Surgery ,RD1-811 - Published
- 2021
- Full Text
- View/download PDF
12. Persufflation—Current State of Play
- Author
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Aaron John Buhagiar, Leo Freitas, and William E. Scott
- Subjects
gaseous oxygen perfusion ,hypothermic reconditioning ,organ preservation ,organ perfusion ,persufflation ,VSOP ,Surgery ,RD1-811 - Abstract
With the ever-increasing disparity between the number of patients waiting for organ transplants and the number organs available, some patients are unable to receive life-saving transplantation in time. The present, widely-used form of preservation is proving to be incapable of maintaining organ quality during long periods of preservation and meeting the needs of an ever-changing legislative and transplantation landscape. This has led to the need for improved preservation techniques. One such technique that has been extensively researched is gaseous oxygen perfusion or Persufflation (PSF). This method discovered in the early 20th century has shown promise in providing both longer term preservation and organ reconditioning capabilities for multiple organs including the liver, kidneys, and pancreas. PSF utilises the organs own vascular network to provide oxygen to the organ tissue and maintain metabolism during preservation to avoid hypoxic damage. This review delves into the history of this technique, its multiple different approaches and uses, as well as in-depth discussion of work published in the past 15 years. Finally, we discuss exciting commercial developments which may help unlock the potential for this technique to be applied at scale.
- Published
- 2021
- Full Text
- View/download PDF
13. Trends and Obstacles to Implement Dynamic Perfusion Concepts for Clinical Liver Transplantation: Results from a Global Web-Based Survey
- Author
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Alessandro Parente, Mauricio Flores Carvalho, Rebecca Panconesi, Yuri L. Boteon, Riccardo De Carlis, Philipp Dutkowski, Paolo Muiesan, Daniele Dondossola, and Andrea Schlegel
- Subjects
liver transplantation ,organ perfusion ,dynamic organ preservation ,survey ,Medicine - Abstract
Background: Organ perfusion technology is increasingly used in many countries, with a focus, however, on the Western world. This study investigates the current international trends and obstacles to the broader routine implementation of dynamic perfusion concepts in liver transplantation. Methods: A web-based anonymous survey was launched in 2021. Experts of all involved specializations from 70 centers in 34 countries were contacted, based on the published literature and experience in the field of abdominal organ perfusion. Results: Overall, 143 participants from 23 countries completed the survey. Most respondents were male (67.8%) and transplant surgeons (64.3%) working at university hospitals (67.9%). The majority had experience with organ perfusion (82%), applying mainly hypothermic machine perfusion (HMP; 38%) and other concepts. While most (94.4%) expect a higher utilization of marginal organs with machine perfusion, the majority considers HMP the best technique to reduce liver discard-rates. While most respondents (90%) believed machine perfusion should be fully commissioned, the lack of funding (34%) and knowledge (16%) as well as limited staff (19%) were the three main obstacles to a routine clinical implementation. Conclusion: Although dynamic preservation concepts are increasingly used in clinical practice, significant challenges remain. Specific financial pathways, uniform regulations, and tight collaborations among involved experts are needed to achieve wider global clinical use.
- Published
- 2023
- Full Text
- View/download PDF
14. Heterogeneous impact of hypotension on organ perfusion and outcomes: a narrative review.
- Author
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Meng, Lingzhong
- Subjects
- *
HYPOTENSION , *BLOOD pressure , *CARDIOVASCULAR system , *PERFUSION , *VASCULAR resistance , *SURGICAL complications , *BLOOD circulation , *DISEASE complications - Abstract
Arterial blood pressure is the driving force for organ perfusion. Although hypotension is common in acute care, there is a lack of accepted criteria for its definition. Most practitioners regard hypotension as undesirable even in situations that pose no immediate threat to life, but hypotension does not always lead to unfavourable outcomes based on experience and evidence. Thus efforts are needed to better understand the causes, consequences, and treatments of hypotension. This narrative review focuses on the heterogeneous underlying pathophysiological bases of hypotension and their impact on organ perfusion and patient outcomes. We propose the iso-pressure curve with hypotension and hypertension zones as a way to visualize changes in blood pressure. We also propose a haemodynamic pyramid and a pressure-output-resistance triangle to facilitate understanding of why hypotension can have different pathophysiological mechanisms and end-organ effects. We emphasise that hypotension does not always lead to organ hypoperfusion; to the contrary, hypotension may preserve or even increase organ perfusion depending on the relative changes in perfusion pressure and regional vascular resistance and the status of blood pressure autoregulation. Evidence from RCTs does not support the notion that a higher arterial blood pressure target always leads to improved outcomes. Management of blood pressure is not about maintaining a prespecified value, but rather involves ensuring organ perfusion without undue stress on the cardiovascular system. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
15. Impact of concomitant vasoactive treatment and mechanical left ventricular unloading in a porcine model of profound cardiogenic shock
- Author
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Nanna L. J. Udesen, Ole K. L. Helgestad, Ann B. S. Banke, Peter H. Frederiksen, Jakob Josiassen, Lisette O. Jensen, Henrik Schmidt, Elazer R. Edelman, Brian Y. Chang, Hanne B. Ravn, and Jacob E. Møller
- Subjects
Cardiogenic shock ,Acute myocardial infarction ,Vasopressor ,Mechanical circulatory support ,Cardiac work ,Organ perfusion ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Concomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP). Objective To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP. Methods CS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 μg/kg/min), epinephrine (0.10 μg/kg/min), or dopamine (10 μg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 μg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO2), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression. Results All catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 103 (mmHg × mL)/min [95% CI (174.1, 509.5), p
- Published
- 2020
- Full Text
- View/download PDF
16. Renal resistive index: a new reversible tool for the early diagnosis and evaluation of organ perfusion in critically ill patients: a case report
- Author
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Antonio Anile, Silvia Ferrario, Lorena Campanello, Maria Antonietta Orban, and Giacomo Castiglione
- Subjects
Renal Doppler Resistive Index (RRI) ,Organ perfusion ,Fluid challenge ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background We reported a case of early detection of peripheral hypoperfusion trough the evaluation of a new index in intensive care: Renal Doppler Resistive Index (RRI). Case presentation We admitted a 76-year-old man who underwent ileostomy and hernioplasty because of an intestinal occlusion due to obstructive strangulated right inguinal hernia. The post-operative period was characterised by hemodynamic instability and he needed an invasive hemodynamic monitoring, administration of vasopressors and continuous renal replacement therapy (CRRT). Then, hemodynamic stability was obtained and vasopressors interrupted. RRI was lower than 0.7. In the eleventh post-operative day, despite stable macrocirculatory parameters, we found increased values of RRI. An abdomen ultrasound first and then a CT scan revealed the presence of bleeding from the previous ileostomy. Hence, the patient immediately underwent another surgical operation. Conclusions RRI modification appears to be more precocious than any other hemodynamic, microcirculatory and metabolic parameter routinely used. RRI has been widely used to assess renal function in critically ill patients; now, we presume that RRI could represent a common and useful tool to manage target therapy in critical condition.
- Published
- 2019
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- View/download PDF
17. Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation
- Author
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Valentina Veloso-Giménez, Rosalba Escamilla, David Necuñir, Rocío Corrales-Orovio, Sergio Riveros, Carlo Marino, Carolina Ehrenfeld, Christian Dani Guzmán, Mauricio P. Boric, Rolando Rebolledo, and José Tomás Egaña
- Subjects
organ preservation ,organ perfusion ,ischemia ,hypoxia ,photosynthetic microorganisms ,Chlamydomonas reinhardtii ,Biotechnology ,TP248.13-248.65 - Abstract
Oxygen is the key molecule for aerobic metabolism, but no animal cells can produce it, creating an extreme dependency on external supply. In contrast, microalgae are photosynthetic microorganisms, therefore, they are able to produce oxygen as plant cells do. As hypoxia is one of the main issues in organ transplantation, especially during preservation, the main goal of this work was to develop the first generation of perfusable photosynthetic solutions, exploring its feasibility for ex vivo organ preservation. Here, the microalgae Chlamydomonas reinhardtii was incorporated in a standard preservation solution, and key aspects such as alterations in cell size, oxygen production and survival were studied. Osmolarity and rheological features of the photosynthetic solution were comparable to human blood. In terms of functionality, the photosynthetic solution proved to be not harmful and to provide sufficient oxygen to support the metabolic requirement of zebrafish larvae and rat kidney slices. Thereafter, isolated porcine kidneys were perfused, and microalgae reached all renal vasculature, without inducing damage. After perfusion and flushing, no signs of tissue damage were detected, and recovered microalgae survived the process. Altogether, this work proposes the use of photosynthetic microorganisms as vascular oxygen factories to generate and deliver oxygen in isolated organs, representing a novel and promising strategy for organ preservation.
- Published
- 2021
- Full Text
- View/download PDF
18. Cardiovascular Activity of Ginkgo biloba—An Insight from Healthy Subjects
- Author
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Henrique Silva and Filipe Gazalho Martins
- Subjects
Ginkgo biloba ,vasodilation ,blood pressure ,organ perfusion ,review ,Biology (General) ,QH301-705.5 - Abstract
Ginkgo biloba is the oldest living tree species in the world. Despite less than encouraging clinical results, extracts from its leaves are among the most used herbal preparations in the prevention and treatment of cardiovascular diseases. Most data on the efficacy of Ginkgo biloba on cardiovascular disease is from clinical studies, with few results from healthy subjects. This paper aims to provide a comprehensive review of the mechanisms underlying the known beneficial cardiovascular activities of Ginkgo biloba. It displays myocardial suppressant and vasorelaxant activities ex vivo, potentiating endothelial-dependent and -independent pathways. It improves perfusion in different vascular beds, namely ocular, cochlear, cutaneous, cerebral, and coronary. Although scarce, evidence suggests that Ginkgo biloba displays a heterogeneous effect on tissue perfusion which is dependent on the individual elimination pathways. It displays an acceptable safety profile, with most reported adverse reactions constituting rare occurrences. Collectively, Ginkgo biloba positively impacts cardiovascular physiology, improving hemodynamics and organ perfusion. In the future, better controlled clinical studies should be performed in order to identify the target populations who may benefit the most from pharmacotherapeutic interventions involving Ginkgo biloba.
- Published
- 2022
- Full Text
- View/download PDF
19. Differential Cytokine Levels during Normothermic Kidney Perfusion with Whole Blood- or Red Blood Cell-Based Perfusates—Results of a Scoping Review and Experimental Study
- Author
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Julie De Beule, Delphine Keppens, Hannelie Korf, and Ina Jochmans
- Subjects
normothermic kidney perfusion ,kidney preservation ,inflammation ,cytokines ,organ perfusion ,Medicine - Abstract
The ideal composition of the perfusate for normothermic kidney perfusion is unknown, though the perfusate commonly used to perfuse human kidneys contains leukocyte-depleted packed red blood cells (RBC), as this is believed to prevent excessive inflammation. We performed a systematic search identifying 19 articles reporting on cytokine levels during normothermic pig or human kidney perfusion. Cytokine levels varied widely across the reported studies. No direct comparisons of perfusate cytokines during perfusion with RBC or whole blood were performed, and no data on how these levels are influenced by ischemia are available. Therefore, we compared perfusate IL-6, IL-1β, TNF-α, TGF-β, IL-10, IL-8, and CCL2 levels during 4 h normothermic pig kidney perfusion with a whole blood- or RBC-based perfusate. Kidneys were exposed to either 1 h of warm or 22 h of cold ischemia. We found no evidence of different perfusate cytokine or gene expression levels in whole blood or RBC perfusions. There was no clear evidence to suggest that cytokine concentrations differ between ischemically injured kidneys and controls. In conclusion, pro-inflammatory and anti-inflammatory cytokines and chemokines are detectable in the perfusate and urine of kidneys undergoing normothermic perfusion. It is unclear how cytokine levels change in different ischemic conditions and whether the use of a leukocyte filter plays a role.
- Published
- 2022
- Full Text
- View/download PDF
20. Portal vein pulsatility: An important sonographic tool assessment of systemic congestion for critical ill patients.
- Author
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Dimopoulos S and Antonopoulos M
- Abstract
In this editorial we comment on the article by Kuwahara et al , published in the recent issue of the World Journal of Cardiology . In this interesting paper, the authors showed a correlation between portal vein pulsatility ratio, examined by bedside ultrasonography, and prognosis of hospitalized patients with acute heart failure. Systemic congestion is being notoriously underdetected in the acutely ill population with conventional methods like clinical examination, biomarkers, central venous pressure estimation and X-rays. However, congestion should be a key therapeutic target due to its deleterious effects to end organ function and subsequently patient prognosis. Doppler flow assessment of the abdominal veins is gaining popularity worldwide, as a valuable tool in estimating comprehensively congestion and giving a further insight into hemodynamics and patient management., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
21. The impact and relevance of techniques and fluids on lung injury in machine perfusion of lungs.
- Author
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Ponholzer F, Dumfarth J, Krapf C, Pircher A, Hautz T, Wolf D, Augustin F, and Schneeberger S
- Subjects
- Humans, Lung, Perfusion methods, Tissue Donors, Lung Injury, Lung Transplantation adverse effects, Lung Transplantation methods
- Abstract
Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated. The variables relate to the engineering and function of the respective perfusion devices, such as the type of pump used, functional, like ventilation modes or physiological (e.g. perfusion solutions). This review reflects on the individual technical and fluid components relevant to EVLP and their respective impact on inflammatory response and outcome. We discuss key components of EVLP protocols and options for further improvement of EVLP in regard to PGD. This review offers an overview of available options for centers establishing an EVLP program and for researchers looking for ways to adapt existing protocols., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ponholzer, Dumfarth, Krapf, Pircher, Hautz, Wolf, Augustin and Schneeberger.)
- Published
- 2024
- Full Text
- View/download PDF
22. Genetic Engineering of the Kidney to Permanently Silence MHC Transcripts During ex vivo Organ Perfusion
- Author
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Yuliia Yuzefovych, Emilio Valdivia, Song Rong, Franziska Hack, Tamina Rother, Jessica Schmitz, Jan Hinrich Bräsen, Dirk Wedekind, Cyril Moers, Nadine Wenzel, Faikah Gueler, Rainer Blasczyk, and Constanca Figueiredo
- Subjects
transplantation - kidney ,organ engineering ,HLA ,gene therapy ,lentiviral vector ,organ perfusion ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Organ gene therapy represents a promising tool to correct diseases or improve graft survival after transplantation. Polymorphic variation of the major histocompatibility complex (MHC) antigens remains a major obstacle to long-term graft survival after transplantation. Previously, we demonstrated that MHC-silenced cells are protected against allogeneic immune responses. We also showed the feasibility to silence MHC in the lung. Here, we aimed at the genetic engineering of the kidney toward permanent silencing of MHC antigens in a rat model. We constructed a sub-normothermic ex vivo perfusion system to deliver lentiviral vectors encoding shRNAs targeting β2-microglobulin and the class II transactivator to the kidney. In addition, the vector contained the sequence for a secreted nanoluciferase. After kidney transplantation (ktx), we detected bioluminescence in the plasma and urine of recipients of an engineered kidney during the 6 weeks of post-transplant monitoring, indicating a stable transgene expression. Remarkably, transcript levels of β2-microglobulin and the class II transactivator were decreased by 70% in kidneys expressing specific shRNAs. Kidney genetic modification did not cause additional cell death compared to control kidneys after machine perfusion. Nevertheless, cytokine secretion signatures were altered during perfusion with lentiviral vectors as revealed by an increase in the secretion of IL-10, MIP-1α, MIP-2, IP-10, and EGF and a decrease in the levels of IL-12, IL-17, MCP-1, and IFN-γ. Biodistribution assays indicate that the localization of the vector was restricted to the graft. This study shows the potential to generate immunologically invisible kidneys showing great promise to support graft survival after transplantation and may contribute to reduce the burden of immunosuppression.
- Published
- 2020
- Full Text
- View/download PDF
23. Is the Sympathetic System Detrimental in the Setting of Septic Shock, with Antihypertensive Agents as a Counterintuitive Approach? A Clinical Proposition
- Author
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Fabrice Petitjeans, Alain Geloen, Cyrille Pichot, Sandrine Leroy, Marco Ghignone, and Luc Quintin
- Subjects
septic shock ,refractory septic shock ,circulation ,microcirculation ,organ perfusion ,permissive hypotension ,Medicine - Abstract
Mortality in the setting of septic shock varies between 20% and 100%. Refractory septic shock leads to early circulatory failure and carries the worst prognosis. The pathophysiology is poorly understood despite studies of the microcirculatory defects and the immuno-paralysis. The acute circulatory distress is treated with volume expansion, administration of vasopressors (usually noradrenaline: NA), and inotropes. Ventilation and anti-infectious strategy shall not be discussed here. When circulation is considered, the literature is segregated between interventions directed to the systemic circulation vs. interventions directed to the micro-circulation. Our thesis is that, after stabilization of the acute cardioventilatory distress, the prolonged sympathetic hyperactivity is detrimental in the setting of septic shock. Our hypothesis is that the sympathetic hyperactivity observed in septic shock being normalized towards baseline activity will improve the microcirculation by recoupling the capillaries and the systemic circulation. Therefore, counterintuitively, antihypertensive agents such as beta-blockers or alpha-2 adrenergic agonists (clonidine, dexmedetomidine) are useful. They would reduce the noradrenaline requirements. Adjuncts (vitamins, steroids, NO donors/inhibitors, etc.) proposed to normalize the sepsis-evoked vasodilation are not reviewed. This itemized approach (systemic vs. microcirculation) requires physiological and epidemiological studies to look for reduced mortality.
- Published
- 2021
- Full Text
- View/download PDF
24. Organ Procurement in the Brain Dead Donors Without In Vivo Cold Perfusion: A Novel Technique.
- Author
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Rastogi, Amit N., Yadav, Sanjay K., and Soin, Arvinder S.
- Subjects
- *
PERFUSION , *ABDOMINAL aorta , *BRAIN death , *ILIAC artery , *KIDNEYS , *KIDNEY exchange - Abstract
We describe our technique of ex vivo organ perfusion and procurement in donation after deceased brain death (DBD) donors. This technique comprises warm dissection of liver, kidneys, and heart, in hemodynamically stable DBD donors and perfusing them ex vivo. The cardiac and abdominal dissection can take place simultaneously. As a precaution, the iliac arteries and the abdominal aorta are dissected and kept ready for rapid cannulation and perfusion, should the donor become unstable at any stage. The liver dissection is in principle similar to living donor hepatectomy, where portal dissection is combined with supra and infrahepatic caval dissection to completely mobilize liver to allow it to be removed and perfused ex vivo. The renal dissection is done after hepatic dissection is complete. The sequence of recovery of organ was modified where kidneys were procured first followed by hepatic and cardiac procurement simultaneously. Twelve multivisceral (liver and kidneys in all and heart in four) procurements have been performed. The average perfusion fluid volume for liver was 3.4 L. All recipients had uneventful postoperative course. Our technique has not affected recipient outcomes and with benefits of less use of preservation solution, shortening bench surgery time, and decreasing the propensity of procurement injuries by avoiding cold-phase dissection. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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25. Genetic Engineering of the Kidney to Permanently Silence MHC Transcripts During ex vivo Organ Perfusion.
- Author
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Yuzefovych, Yuliia, Valdivia, Emilio, Rong, Song, Hack, Franziska, Rother, Tamina, Schmitz, Jessica, Bräsen, Jan Hinrich, Wedekind, Dirk, Moers, Cyril, Wenzel, Nadine, Gueler, Faikah, Blasczyk, Rainer, and Figueiredo, Constanca
- Subjects
GENETIC engineering ,KIDNEYS ,MAJOR histocompatibility complex ,PERFUSION ,TRANSGENE expression - Abstract
Organ gene therapy represents a promising tool to correct diseases or improve graft survival after transplantation. Polymorphic variation of the major histocompatibility complex (MHC) antigens remains a major obstacle to long-term graft survival after transplantation. Previously, we demonstrated that MHC-silenced cells are protected against allogeneic immune responses. We also showed the feasibility to silence MHC in the lung. Here, we aimed at the genetic engineering of the kidney toward permanent silencing of MHC antigens in a rat model. We constructed a sub-normothermic ex vivo perfusion system to deliver lentiviral vectors encoding shRNAs targeting β2-microglobulin and the class II transactivator to the kidney. In addition, the vector contained the sequence for a secreted nanoluciferase. After kidney transplantation (ktx), we detected bioluminescence in the plasma and urine of recipients of an engineered kidney during the 6 weeks of post-transplant monitoring, indicating a stable transgene expression. Remarkably, transcript levels of β2-microglobulin and the class II transactivator were decreased by 70% in kidneys expressing specific shRNAs. Kidney genetic modification did not cause additional cell death compared to control kidneys after machine perfusion. Nevertheless, cytokine secretion signatures were altered during perfusion with lentiviral vectors as revealed by an increase in the secretion of IL-10, MIP-1α, MIP-2, IP-10, and EGF and a decrease in the levels of IL-12, IL-17, MCP-1, and IFN-γ. Biodistribution assays indicate that the localization of the vector was restricted to the graft. This study shows the potential to generate immunologically invisible kidneys showing great promise to support graft survival after transplantation and may contribute to reduce the burden of immunosuppression. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
26. Contrast-enhanced computed tomography of the liver, gall bladder and urogenital tract in female red-eared terrapins (Trachemys scripta elegans)
- Author
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V. Sochorcova, P. Proks, E. Cermakova, and Z. Knotek
- Subjects
chelonians ,computed tomography ,contrast medium ,organ perfusion ,liver ,kidneys ,Veterinary medicine ,SF600-1100 - Abstract
The aim of the present study was to evaluate the feasibility of contrast-enhanced computed tomography for organ morphology and perfusion in five captive terrapins. Native scans were performed and afterwards an iodinated non-ionic contrast media was manually administered through the jugular vein catheter. Post-contrast CT scans were taken 20 (T20), 60 (T60) and 180 (T180) seconds after the contrast medium administration. Maximum contrast enhancement of the kidneys and the liver was detected at T20 and T60, respectively. The gall bladder content, the urinary bladder content and ovarian follicles were all without contrast enhancement in all five terrapins. Gall bladder wall thickness was 0.9 mm in all terrapins. Enhancement of the gall bladder wall in post-contrast studies was considered excellent, good or poor in two terrapins, two terrapins and one terrapin, respectively, with a mean score of 1.8 ± 0.84 over all contrast studies. Enhancement of the ureters in post-contrast studies was considered excellent in all terrapins in all contrast studies. Peak aortic enhancement was reached 20 seconds after contrast medium administration with the peak enhancement of 213.5 ± 41 HU in four terrapins and 560 HU in one terrapin. Peak hepatic vein enhancement after contrast medium administration was recorded 20 and 60 seconds in two and three terrapins, respectively. In conclusion, contrast-enhanced computed tomography proved to be a valuable method for clinical examination of the liver, gall bladder, kidneys, ureters, urinary bladder and ovarian follicles in red-eared terrapins.
- Published
- 2017
- Full Text
- View/download PDF
27. Perioperative Perfusion of Allografts with Anti-Human T-lymphocyte Globulin Does Not Improve Outcome Post Liver Transplantation—A Randomized Placebo-Controlled Trial
- Author
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Paul Viktor Ritschl, Julia Günther, Lena Hofhansel, Stefanie Ernst, Susanne Ebner, Arne Sattler, Sascha Weiß, Annemarie Weissenbacher, Rupert Oberhuber, Benno Cardini, Robert Öllinger, Matthias Biebl, Christian Denecke, Christian Margreiter, Thomas Resch, Stefan Schneeberger, Manuel Maglione, Katja Kotsch, and Johann Pratschke
- Subjects
liver transplantation ,ATLG ,organ perfusion ,organ pretreatment ,machine perfusion ,polyclonal antibody ,Medicine - Abstract
Due to the lack of suitable organs transplant surgeons have to accept unfavorable extended criteria donor (ECD) organs. Recently, we demonstrated that the perfusion of kidney organs with anti-human T-lymphocyte globulin (ATLG) prior to transplantation ameliorates ischemia-reperfusion injury (IRI). Here, we report on the results of perioperative ATLG perfusion in a randomized, single-blinded, placebo-controlled, feasibility trial (RCT) involving 30 liver recipients (LTx). Organs were randomly assigned for perfusion with ATLG/Grafalon® (AP) (n = 16) or saline only (control perfusion = CP) (n = 14) prior to implantation. The primary endpoint was defined as graft function reflected by aspartate transaminase (AST) values at day 7 post-transplantation (post-tx). With respect to the primary endpoint, no significant differences in AST levels were shown in the intervention group at day 7 (AP: 53.0 ± 21.3 mg/dL, CP: 59.7 ± 59.2 mg/dL, p = 0.686). Similarly, exploratory analysis of secondary clinical outcomes (e.g., patient survival) and treatment-specific adverse events revealed no differences between the study groups. Among liver transplant recipients, pre-operative organ perfusion with ATLG did not improve short-term outcomes, compared to those who received placebo perfusion. However, ATLG perfusion of liver grafts was proven to be a safe procedure without the occurrence of relevant adverse events.
- Published
- 2021
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28. Identification and quantification of gold engineered nanomaterials and impaired fluid transfer across the rat placenta via ex vivo perfusion
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J.N. D’Errico, C. Doherty, S.B. Fournier, N. Renkel, S. Kallontzi, M. Goedken, L. Fabris, B. Buckley, and P.A. Stapleton
- Subjects
Placenta ,Engineered nanomaterial ,Organ perfusion ,Gold nanomaterials ,ICP-MS ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Development and implementation of products incorporating nanoparticles are occurring at a rapid pace. These particles are widely utilized in domestic, occupational, and biomedical applications. Currently, it is unclear if pregnant women will be able to take advantage of the potential biomedical nanoproducts out of concerns associated with placental transfer and fetal interactions. We recently developed an ex vivo rat placental perfusion technique to allow for the evaluation of xenobiotic transfer and placental physiological perturbations. In this study, a segment of the uterine horn and associated placenta was isolated from pregnant (gestational day 20) Sprague-Dawley rats and placed into a modified pressure myography vessel chamber. The proximal and distal ends of the maternal uterine artery and the vessels of the umbilical cord were cannulated, secured, and perfused with physiological salt solution (PSS). The proximal uterine artery and umbilical artery were pressurized at 80 mmHg and 50 mmHg, respectively, to allow countercurrent flow through the placenta. After equilibration, a single 900 μL bolus dose of 20 nm gold engineered nanoparticles (Au-ENM) was introduced into the proximal maternal artery. Distal uterine and umbilical vein effluents were collected every 10 min for 180 min to measure placental fluid dynamics. The quantification of Au-ENM transfer was conducted via inductively coupled plasma mass spectrometry (ICP-MS). Overall, we were able to measure Au-ENM within uterine and umbilical effluent with 20 min of material infusion. This novel methodology may be widely incorporated into studies of pharmacology, toxicology, and placental physiology.
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- 2019
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29. Differential Cytokine Levels during Normothermic Kidney Perfusion with Whole Blood- or Red Blood Cell-Based Perfusates-Results of a Scoping Review and Experimental Study
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Ina Jochmans, Julie De Beule, Delphine Keppens, and Hannelie Korf
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normothermic kidney perfusion ,kidney preservation ,inflammation ,cytokines ,organ perfusion ,General Medicine - Abstract
The ideal composition of the perfusate for normothermic kidney perfusion is unknown, though the perfusate commonly used to perfuse human kidneys contains leukocyte-depleted packed red blood cells (RBC), as this is believed to prevent excessive inflammation. We performed a systematic search identifying 19 articles reporting on cytokine levels during normothermic pig or human kidney perfusion. Cytokine levels varied widely across the reported studies. No direct comparisons of perfusate cytokines during perfusion with RBC or whole blood were performed, and no data on how these levels are influenced by ischemia are available. Therefore, we compared perfusate IL-6, IL-1β, TNF-α, TGF-β, IL-10, IL-8, and CCL2 levels during 4 h normothermic pig kidney perfusion with a whole blood- or RBC-based perfusate. Kidneys were exposed to either 1 h of warm or 22 h of cold ischemia. We found no evidence of different perfusate cytokine or gene expression levels in whole blood or RBC perfusions. There was no clear evidence to suggest that cytokine concentrations differ between ischemically injured kidneys and controls. In conclusion, pro-inflammatory and anti-inflammatory cytokines and chemokines are detectable in the perfusate and urine of kidneys undergoing normothermic perfusion. It is unclear how cytokine levels change in different ischemic conditions and whether the use of a leukocyte filter plays a role. ispartof: Journal Of Clinical Medicine vol:11 issue:22 pages:1-11 ispartof: location:Switzerland status: Published online
- Published
- 2022
30. A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation
- Abstract
Background & Aims: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. Methods: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. Results: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk grou
- Published
- 2022
31. Persufflation—Current State of Play
- Author
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William E. Scott, Aaron John Buhagiar, and Leo Freitas
- Subjects
hypothermic reconditioning ,medicine.medical_specialty ,RD1-811 ,Gaseous oxygen ,business.industry ,persufflation ,Transplantation ,gaseous oxygen perfusion ,Vascular network ,Medicine ,Surgery ,organ perfusion ,organ preservation ,business ,Intensive care medicine ,VSOP - Abstract
With the ever-increasing disparity between the number of patients waiting for organ transplants and the number organs available, some patients are unable to receive life-saving transplantation in time. The present, widely-used form of preservation is proving to be incapable of maintaining organ quality during long periods of preservation and meeting the needs of an ever-changing legislative and transplantation landscape. This has led to the need for improved preservation techniques. One such technique that has been extensively researched is gaseous oxygen perfusion or Persufflation (PSF). This method discovered in the early 20th century has shown promise in providing both longer term preservation and organ reconditioning capabilities for multiple organs including the liver, kidneys, and pancreas. PSF utilises the organs own vascular network to provide oxygen to the organ tissue and maintain metabolism during preservation to avoid hypoxic damage. This review delves into the history of this technique, its multiple different approaches and uses, as well as in-depth discussion of work published in the past 15 years. Finally, we discuss exciting commercial developments which may help unlock the potential for this technique to be applied at scale.
- Published
- 2021
32. Contrast-enhanced computed tomography of the liver, gall bladder and urogenital tract in female red-eared terrapins (Trachemys scripta elegans).
- Author
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SOCHORCOVA, V., PROKS, P., CERMAKOVA, E., and KNOTEK, Z.
- Subjects
- *
COMPUTED tomography , *GENITOURINARY organs , *RED-eared slider , *MORPHOLOGY , *PERFUSION - Abstract
The aim of the present study was to evaluate the feasibility of contrast-enhanced computed tomography for organ morphology and perfusion in five captive terrapins. Native scans were performed and afterwards an iodinated non-ionic contrast media was manually administered through the jugular vein catheter. Post-contrast CT scans were taken 20 (T20), 60 (T60) and 180 (T180) seconds after the contrast medium administration. Maximum contrast enhancement of the kidneys and the liver was detected at T20 and T60, respectively. The gall bladder content, the urinary bladder content and ovarian follicles were all without contrast enhancement in all five terrapins. Gall bladder wall thickness was 0.9 mm in all terrapins. Enhancement of the gall bladder wall in post-contrast studies was considered excellent, good or poor in two terrapins, two terrapins and one terrapin, respectively, with a mean score of 1.8 ± 0.84 over all contrast studies. Enhancement of the ureters in post-contrast studies was considered excellent in all terrapins in all contrast studies. Peak aortic enhancement was reached 20 seconds after contrast medium administration with the peak enhancement of 213.5 ± 41 HU in four terrapins and 560 HU in one terrapin. Peak hepatic vein enhancement after contrast medium administration was recorded 20 and 60 seconds in two and three terrapins, respectively. In conclusion, contrast-enhanced computed tomography proved to be a valuable method for clinical examination of the liver, gall bladder, kidneys, ureters, urinary bladder and ovarian follicles in red-eared terrapins. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
33. Expanding controlled donation after the circulatory determination of death
- Author
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Alexandra K. Glazier, Alexander Morgan Capron, Dirk Van Raemdonck, Kumud Dhital, Didier Ledoux, James F. Markmann, Shaf Keshavjee, Constantino Fondevila, Stefan G. Tullius, Alexander R. Manara, Nancy L. Ascher, Jeffrey M. Singh, Dale Gardiner, Francis L. Delmonico, James M. DuBois, James L. Bernat, Robert J. Porte, Andrew McGee, Sam D. Shemie, Beatriz Domínguez-Gil, Sarah A. Hosgood, Galen V. Henderson, Eduardo Miñambres, Domínguez-Gil, Beatriz [0000-0002-5695-8993], Hosgood, Sarah [0000-0002-8039-143X], Apollo - University of Cambridge Repository, and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
Donation after the circulatory determination of death ,medicine.medical_specialty ,Statement (logic) ,Conference Reports and Expert Panel ,Perfusion scanning ,Normothermic regional perfusion ,Critical Care and Intensive Care Medicine ,Organ transplantation ,Tissue and organ procurement ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Anesthesiology ,Humans ,Medicine ,Organ donation ,Intensive care medicine ,business.industry ,Correction ,030208 emergency & critical care medicine ,Determination of death ,Tissue Donors ,Organ repair ,Organ perfusion ,Death ,Transplantation ,Withdrawal of life-sustaining therapy ,030228 respiratory system ,Donation ,Quality of Life ,business - Abstract
A decision to withdraw life-sustaining treatment (WLST) is derived by a conclusion that further treatment will not enable a patient to survive or will not produce a functional outcome with acceptable quality of life that the patient and the treating team regard as beneficial. Although many hospitalized patients die under such circumstances, controlled donation after the circulatory determination of death (cDCDD) programs have been developed only in a reduced number of countries. This International Collaborative Statement aims at expanding cDCDD in the world to help countries progress towards self-sufficiency in transplantation and offer more patients the opportunity of organ donation. The Statement addresses three fundamental aspects of the cDCDD pathway. First, it describes the process of determining a prognosis that justifies the WLST, a decision that should be prior to and independent of any consideration of organ donation and in which transplant professionals must not participate. Second, the Statement establishes the permanent cessation of circulation to the brain as the standard to determine death by circulatory criteria. Death may be declared after an elapsed observation period of 5 min without circulation to the brain, which confirms that the absence of circulation to the brain is permanent. Finally, the Statement highlights the value of perfusion repair for increasing the success of cDCDD organ transplantation. cDCDD protocols may utilize either in situ or ex situ perfusion consistent with the practice of each country. Methods to accomplish the in situ normothermic reperfusion of organs must preclude the restoration of brain perfusion to not invalidate the determination of death. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-020-06341-7.
- Published
- 2021
34. A new strategy and system for the ex vivo ovary perfusion and cryopreservation: An innovation.
- Author
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Mohamed, Mohamed Shehata Ali
- Subjects
- *
CRYOPRESERVATION of organs, tissues, etc. , *OVARIAN transplantation , *PERFUSION , *REPERFUSION injury , *FERTILITY preservation , *CANCER chemotherapy , *OVARIES - Abstract
Children and young adults, who suffer from cancer, receive gonadotoxic therapy, which destroys their fertile abilities after survival. Ovarian cryopreservation and transplantation provide the promising solution to this problem, where the ovary can be removed before the gonadotoxic therapy and reimplanted after patient's survival, where the ovary is to be cryopreserved during the period of the therapy. However, cryopreservation of the whole ovary is still facing great obstacles, namely the ischemic reperfusion injury and the defective cryopreservation related to the defective ability to universally deliver the cryopreservation/warming solutions through the ovarian vascular bed. Meanwhile, the currently applied technique of ovarian tissue cryopreservation provides limited follicular recovery because many follicles are lost until the establishment of revascularization post-transplantation. To solve the problems, an innovative system has been developed to insure immediate and universal delivery of the cryopreservation/warming solutions to the graft, in addition to keeping the graft under continuous perfusion before and after cryopreservation, minimizing any chance for microthrombi formation or ischemiareperfusion. This innovative system can be applied in the following surgical and clinical interventions: 1) Allogeneic ovarian transplantation; 2) Preservation of fertility after systemic chemotherapy or bone marrow transplantation in young females, where the ovaries could be removed before the therapy and exposed to the adequate cryopreservation provided by the system till re-implantation after the patient's survival; 3) The system is also suitable for the corresponding applications on the testicles. [ABSTRACT FROM AUTHOR]
- Published
- 2017
35. Expanding controlled donation after the circulatory determination of death : statement from an international collaborative
- Abstract
A decision to withdraw life-sustaining treatment (WLST) is derived by a conclusion that further treatment will not enable a patient to survive or will not produce a functional outcome with acceptable quality of life that the patient and the treating team regard as beneficial. Although many hospitalized patients die under such circumstances, controlled donation after the circulatory determination of death (cDCDD) programs have been developed only in a reduced number of countries. This International Collaborative Statement aims at expanding cDCDD in the world to help countries progress towards self-sufficiency in transplantation and offer more patients the opportunity of organ donation. The Statement addresses three fundamental aspects of the cDCDD pathway. First, it describes the process of determining a prognosis that justifies the WLST, a decision that should be prior to and independent of any consideration of organ donation and in which transplant professionals must not participate. Second, the Statement establishes the permanent cessation of circulation to the brain as the standard to determine death by circulatory criteria. Death may be declared after an elapsed observation period of 5 min without circulation to the brain, which confirms that the absence of circulation to the brain is permanent. Finally, the Statement highlights the value of perfusion repair for increasing the success of cDCDD organ transplantation. cDCDD protocols may utilize either in situ or ex situ perfusion consistent with the practice of each country. Methods to accomplish the in situ normothermic reperfusion of organs must preclude the restoration of brain perfusion to not invalidate the determination of death.
- Published
- 2021
36. Perioperative Perfusion of Allografts with Anti-Human T-lymphocyte Globulin Does Not Improve Outcome Post Liver Transplantation-A Randomized Placebo-Controlled Trial
- Author
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Ritschl, Paul Viktor, Günther, Julia, Hofhansel, Lena, Ernst, Stefanie, Ebner, Susanne, Sattler, Arne, Weiß, Sascha, Weissenbacher, Annemarie, Oberhuber, Rupert, Cardini, Benno, Öllinger, Robert, Biebl, Matthias, Denecke, Christian, Margreiter, Christian, Resch, Thomas, Schneeberger, Stefan, Maglione, Manuel, Kotsch, Katja, and Pratschke, Johann
- Subjects
liver transplantation ,machine perfusion ,ATLG ,Medicine ,organ pretreatment ,organ perfusion ,polyclonal antibody ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit ,Article - Abstract
Journal of Clinical Medicine 10(13), 2816 (2021). doi:10.3390/jcm10132816 special issue: "Special Issue "Liver Transplantation: Improving Results under Worsening Conditions" / Special Issue Editor: Prof. Dr. Robert Öllinger, Guest Editor", Published by MDPI, Basel
- Published
- 2021
37. A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation
- Author
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Bart van Hoek, Riccardo De Carlis, Philipp Dutkowski, Gonzalo Sapisochin, Luciano De Carlis, Danny van der Helm, Juan Carlos Caicedo, Erin Winter, Wojciech G. Polak, Humberto Bohorquez, Gabriel C. Oniscu, Fabrizio Di Benedetto, Amna Daud, Paolo Muiesan, V. Lucidi, Daniel Borja-Cacho, C. Burcin Taner, Nicolas Meurisse, Jacques Pirenne, Jeannette Widmer, Amelia J. Hessheimer, Matteo Ravaioli, Wayel Jassem, Mauricio Flores Carvalho, Aad P. van der Berg, Ahmed Sherif, Michele Colledan, Amit Nair, Renato Romagnoli, Diethard Monbaliu, Desislava Germanova, Cristiano Quintini, Andre Gorgen, Matteo Cescon, Sofie Vets, Marco P. A. W. Claasen, Massimo Malagó, Peter Lodge, Stefania Camagni, Kristopher P. Croome, Giorgio Rossi, Robert J. Porte, Ian P.J. Alwayn, Rebecca Panconesi, Maite Paolucci, Philipp Kron, Andrea Schlegel, Vincent E de Meijer, Annalisa Dolcet, Ina Jochmans, Charles Miller, Margherita Carbonaro, Pierre-Alain Clavien, Jan Nm Ijzermans, Constantino Fondevila, Damiano Patrono, Daniele Dondossola, Olivier Detry, Mohamed Elsharif, Koji Tomiyama, Alessandro Parente, Nigel Heaton, Herold J. Metselaar, Matteo Mueller, Tiziana Olivieri, George E. Loss, Marjolein van Reeven, Sarah Croome, Magdy Attia, Roberto Hernandez-Alejandro, Otto B. van Leeuwen, Groningen Institute for Organ Transplantation (GIOT), Center for Liver, Digestive and Metabolic Diseases (CLDM), Schlegel, A, van Reeven, M, Croome, K, Parente, A, Dolcet, A, Widmer, J, Meurisse, N, De Carlis, R, Hessheimer, A, Jochmans, I, Mueller, M, van Leeuwen, O, Nair, A, Tomiyama, K, Sherif, A, Elsharif, M, Kron, P, van der Helm, D, Borja-Cacho, D, Bohorquez, H, Germanova, D, Dondossola, D, Olivieri, T, Camagni, S, Gorgen, A, Patrono, D, Cescon, M, Croome, S, Panconesi, R, Flores Carvalho, M, Ravaioli, M, Caicedo, J, Loss, G, Lucidi, V, Sapisochin, G, Romagnoli, R, Jassem, W, Colledan, M, De Carlis, L, Rossi, G, Di Benedetto, F, Miller, C, van Hoek, B, Attia, M, Lodge, P, Hernandez-Alejandro, R, Detry, O, Quintini, C, Oniscu, G, Fondevila, C, Malagó, M, Pirenne, J, Ijzermans, J, Porte, R, Dutkowski, P, Taner, C, Heaton, N, Clavien, P, Polak, W, Muiesan, P, Surgery, Gastroenterology & Hepatology, Schlegel A., van Reeven M., Croome K., Parente A., Dolcet A., Widmer J., Meurisse N., De Carlis R., Hessheimer A., Jochmans I., Mueller M., van Leeuwen O.B., Nair A., Tomiyama K., Sherif A., Elsharif M., Kron P., van der Helm D., Borja-Cacho D., Bohorquez H., Germanova D., Dondossola D., Olivieri T., Camagni S., Gorgen A., Patrono D., Cescon M., Croome S., Panconesi R., Carvalho M.F., Ravaioli M., Caicedo J.C., Loss G., Lucidi V., Sapisochin G., Romagnoli R., Jassem W., Colledan M., De Carlis L., Rossi G., Di Benedetto F., Miller C.M., van Hoek B., Attia M., Lodge P., Hernandez-Alejandro R., Detry O., Quintini C., Oniscu G.C., Fondevila C., Malago M., Pirenne J., IJzermans J.N.M., Porte R.J., Dutkowski P., Taner C.B., Heaton N., Clavien P.-A., Polak W.G., Muiesan P., Alwayn I.P.J., van der Berg A.P., Carbonaro M., Claasen M., Daud A., de Meijer V.E., Metselaar H.J., Monbaliu D., Paolucci M., Vets S., and Winter E.
- Subjects
Male ,Organ Dysfunction Scores ,benchmarking ,Donation after circulatory death ,liver transplantation ,morbidity ,organ perfusion ,risk analysis ,IMPACT ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Liver transplantation ,GUIDELINES ,ALLOCATION ,law.invention ,Cohort Studies ,Postoperative Complications ,PROPOSAL ,Interquartile range ,law ,Outcome Assessment, Health Care ,risk analysi ,Mortality rate ,EXTENDED-CRITERIA DONORS ,Shock ,Middle Aged ,Editorial from the ACHBPT ,Intensive care unit ,CARDIAC DEATH ,Area Under Curve ,Cohort ,Female ,medicine.medical_specialty ,Tissue and Organ Procurement ,BILIARY COMPLICATIONS ,Cold storage ,CLASSIFICATION ,Internal medicine ,SCORE ,medicine ,Humans ,Renal replacement therapy ,Aged ,Proportional Hazards Models ,GRAFT-SURVIVAL ,Hepatology ,business.industry ,ROC Curve ,Complication ,business - Abstract
BACKGROUND: To identify the best possible outcomes in liver transplantation from donation after circulatory death donors (DCD) and to propose outcome values, which serve as reference for individual liver recipients or patient groups.METHODS: Based on 2219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1012 low-risk, primary, adult liver transplantations with a laboratory MELD of ≤20points, receiving a DCD liver with a total donor warm ischemia time of ≤30minutes and asystolic donor warm ischemia time of ≤15minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the Comprehensive Complication Index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered.RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centers. The one-year retransplant and mortality rate was 5.23% and 9.01%, respectively. Within the first year of follow-up, 51.1% of recipients developed at least one major complication (≥Clavien-Dindo-Grade-III). Benchmark cut-offs were ≤3days and ≤16days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade-III), ≤16.8% for ischemic cholangiopathy, and ≤38.9CCI points at one-year posttransplant. Comparisons with higher risk groups showed more complications and impaired graft survival, outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk.CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high with more than half of recipients developing severe complications during 1-year follow-up. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups, and provide a valid comparator cohort for future clinical trials.LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2219 liver transplantations following controlled DCD donation in 17 centres worldwide. The following benchmark cut-offs for the most relevant outcome parameters were developed: ICU and hospital stay: ≤3 and ≤16 days; primary non function: ≤2.5%; renal replacement therapy: ≤9.6%; ischemic cholangiopathy: ≤16.8% and anastomotic strictures ≤28.4%. One-year graft loss and mortality were defined as ≤14.4% and 9.6%, respectively. Donor and recipient combinations with higher risk had significantly worse outcomes. The use of novel organ perfusion technology achieved similar, good results in this high-risk group with prolonged donor warm ischemia time, when compared to the benchmark cohort.
- Published
- 2021
38. Impact of concomitant vasoactive treatment and mechanical left ventricular unloading in a porcine model of profound cardiogenic shock
- Author
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Udesen, Nanna L. J., Helgestad, Ole K. L., Banke, Ann B. S., Frederiksen, Peter H., Josiassen, Jakob, Jensen, Lisette O., Schmidt, Henrik, Edelman, Elazer R., Chang, Brian Y., Ravn, Hanne B., and Møller, Jacob E.
- Published
- 2020
- Full Text
- View/download PDF
39. Cardiovascular Activity of Ginkgo biloba-An Insight from Healthy Subjects.
- Author
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Silva H and Martins FG
- Abstract
Ginkgo biloba is the oldest living tree species in the world. Despite less than encouraging clinical results, extracts from its leaves are among the most used herbal preparations in the prevention and treatment of cardiovascular diseases. Most data on the efficacy of Ginkgo biloba on cardiovascular disease is from clinical studies, with few results from healthy subjects. This paper aims to provide a comprehensive review of the mechanisms underlying the known beneficial cardiovascular activities of Ginkgo biloba. It displays myocardial suppressant and vasorelaxant activities ex vivo, potentiating endothelial-dependent and -independent pathways. It improves perfusion in different vascular beds, namely ocular, cochlear, cutaneous, cerebral, and coronary. Although scarce, evidence suggests that Ginkgo biloba displays a heterogeneous effect on tissue perfusion which is dependent on the individual elimination pathways. It displays an acceptable safety profile, with most reported adverse reactions constituting rare occurrences. Collectively, Ginkgo biloba positively impacts cardiovascular physiology, improving hemodynamics and organ perfusion. In the future, better controlled clinical studies should be performed in order to identify the target populations who may benefit the most from pharmacotherapeutic interventions involving Ginkgo biloba.
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- 2022
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40. Renal resistive index: a new reversible tool for the early diagnosis and evaluation of organ perfusion in critically ill patients: a case report
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Anile, Antonio, Ferrario, Silvia, Campanello, Lorena, Orban, Maria Antonietta, and Castiglione, Giacomo
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- 2019
- Full Text
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41. Impact of concomitant vasoactive treatment and mechanical left ventricular unloading in a porcine model of profound cardiogenic shock
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Jakob Josiassen, Peter H. Frederiksen, Henrik Schmidt, Jacob E. Møller, Ole Kristian Lerche Helgestad, Ann Banke, Hanne Berg Ravn, Nanna L J Udesen, Lisette O. Jensen, Brian Y. Chang, and Elazer R. Edelman
- Subjects
Shock, Cardiogenic/physiopathology ,medicine.medical_specialty ,Swine ,Dopamine ,Myocardial Infarction ,Shock, Cardiogenic ,Acute myocardial infarction ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Norepinephrine ,Phenylephrine ,03 medical and health sciences ,Catecholamines ,0302 clinical medicine ,Mechanical circulatory support ,Cardiac work ,Internal medicine ,Heart rate ,medicine ,Animals ,Humans ,Myocardial infarction ,Cardiac Output ,Cardiogenic shock ,Impella ,Myocardial Infarction/complications ,business.industry ,Research ,Hemodynamics ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,030208 emergency & critical care medicine ,lcsh:RC86-88.9 ,medicine.disease ,Organ perfusion ,Vasopressor ,Disease Models, Animal ,Hemodynamics/drug effects ,Epinephrine ,Cardiology ,Myocardial infarction complications ,Heart-Assist Devices ,Cardiac Output/drug effects ,business ,Perfusion ,Catecholamines/therapeutic use ,medicine.drug - Abstract
Background Concomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP). Objective To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP. Methods CS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 μg/kg/min), epinephrine (0.10 μg/kg/min), or dopamine (10 μg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 μg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO2), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression. Results All catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 103 (mmHg × mL)/min [95% CI (174.1, 509.5), p 2 significantly improved during all catecholamines. Phenylephrine, a vasoconstrictor, caused a significant increase in cardiac work by 437.8 × 103 (mmHg × mL)/min [95% CI (297.9, 577.6), p p = 0.001), but no significant change in LV stroke work. Also, phenylephrine tended to decrease SvO2 (p = 0.063) and increased arterial lactate levels (p = 0.002). Conclusion Catecholamines increased end-organ perfusion at the expense of increased cardiac work, most by dopamine. However, phenylephrine increased cardiac work with no increase in end-organ perfusion.
- Published
- 2020
42. Анализ осложнений, возникших в периоперационном периоде, при использовании различных режимов инфузионной терапии
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Kursov, Sergii, Lyzohub, Kseniia, and Lyzohub, Mykola
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restrictive fluid resuscitation ,purposeful fluid therapy ,hemodynamics ,vasopressors ,hypovolemia ,organ perfusion ,УДК: 616-005.1-085+616-035.2:616-036.882-08+617.082 ,lcsh:R ,lcsh:Medicine ,рестриктивная жидкостная ресусцитация ,целенаправленная жидкостная терапия ,гемодинамика ,вазопрессоры ,гиповолемия ,органная перфузия - Abstract
Aim: To realize the clinical analysis of post-surgical complications in patients, who received intraoperative infuse therapy by the method of the restrictive mode of fluid resuscitation and purposeful fluid therapy for providing the adequate and stable hemodynamics in perioperative period and also for preventing the complications development.Materials and methods: the study was realized in 176 patients, who underwent surgical interventions in orthopedic oncology. The restrictive mode of fluid resuscitation was applied in 88 cases, and in 88 ones – the purposeful fluid therapy. The central hemodynamics was studied by the method of Cubichek tetrapolar rheography, coagulogram indications, dieresis speed, blood serum creatinine, frequency of postoperative nausea and vomit and enteroparesis were studied.Research results: the frequency of coagulopathy observations at purposeful fluid therapy didn’t reliably exceed the frequency of coagulopathy in patients with the restrictive mode. Patients, who underwent purposeful fluid therapy demonstrated the decrease of dieresis speed, postoperative nausea and vomit and enteroparesis reliably more seldom. At providing purposeful fluid therapy, there was observed the more stable hemodynamics, whereas patients with the restrictive mode of resuscitation reliably more often needed for the additional hemodynamic correction, which needed the use of vasopressors in 67 % of cases and unplanned increase of infusion therapy volume in 36 % of cases.Conclusions: the risk of complications of GIT and kidneys decreases at using purposeful fluid therapy, and the more stable postoperative hemodynamics comparing with the restrictive mode is guaranteed, В статье проведен сравнительный анализ частоты неблагоприятных событий, которые могли быть обусловлены использованием режимов интраоперационной инфузионной терапии, у 176 пациентов, перенесших хирургические вмешательства в онкоортопедии. Было выявлено, что при применении целенаправленной инфузионной терапии уменьшается риск возникновения осложнений со стороны ЖКТ и почек и обеспечивается более стабильная послеоперационная гемодинамика по сравнению с рестриктивным режимом
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- 2017
43. Neonatal hemodynamics: monitoring, data acquisition and analysis.
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Soleymani, Sadaf, Borzage, Matthew, Noori, Shahab, and Seri, Istvan
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NEWBORN infants ,HEMODYNAMICS ,ACQUISITION of data ,BIOLOGICAL monitoring ,INTENSIVE care units ,CARDIOVASCULAR diseases - Abstract
Monitoring of cardiovascular function is critical to both clinical care and research as the use of sophisticated monitoring systems enable us to obtain accurate, reliable and real-time information on developmental hemodynamics in health and disease. Novel approaches to comprehensive hemodynamic monitoring and data acquisition will undoubtedly aid in developing a better understanding of developmental cardiovascular physiology in neonates. In addition, development and use of state-of-the-art, comprehensive hemodynamic monitoring systems enable the recognition of signs of cardiovascular compromise in its early stages, and provide information on the hemodynamic response to treatment in critically ill patients. [ABSTRACT FROM AUTHOR]
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- 2012
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44. Is the Sympathetic System Detrimental in the Setting of Septic Shock, with Antihypertensive Agents as a Counterintuitive Approach? A Clinical Proposition.
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Petitjeans, Fabrice, Geloen, Alain, Pichot, Cyrille, Leroy, Sandrine, Ghignone, Marco, and Quintin, Luc
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- *
SEPTIC shock , *ANTIHYPERTENSIVE agents , *ADRENERGIC agonists , *PATHOLOGICAL physiology , *PROGNOSIS - Abstract
Mortality in the setting of septic shock varies between 20% and 100%. Refractory septic shock leads to early circulatory failure and carries the worst prognosis. The pathophysiology is poorly understood despite studies of the microcirculatory defects and the immuno-paralysis. The acute circulatory distress is treated with volume expansion, administration of vasopressors (usually noradrenaline: NA), and inotropes. Ventilation and anti-infectious strategy shall not be discussed here. When circulation is considered, the literature is segregated between interventions directed to the systemic circulation vs. interventions directed to the micro-circulation. Our thesis is that, after stabilization of the acute cardioventilatory distress, the prolonged sympathetic hyperactivity is detrimental in the setting of septic shock. Our hypothesis is that the sympathetic hyperactivity observed in septic shock being normalized towards baseline activity will improve the microcirculation by recoupling the capillaries and the systemic circulation. Therefore, counterintuitively, antihypertensive agents such as beta-blockers or alpha-2 adrenergic agonists (clonidine, dexmedetomidine) are useful. They would reduce the noradrenaline requirements. Adjuncts (vitamins, steroids, NO donors/inhibitors, etc.) proposed to normalize the sepsis-evoked vasodilation are not reviewed. This itemized approach (systemic vs. microcirculation) requires physiological and epidemiological studies to look for reduced mortality. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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45. Isolated Hemoperfused Slaughterhouse Livers as a Valid Model to Study Hepatotoxicity.
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Grosse-Siestrup, Christian, Pfeffer, Jeanette, Unger, Volker, Nagel, Stefan, Witt, Christian, Fischer, Axel, and Groneberg, David A.
- Subjects
- *
HEPATOTOXICOLOGY , *LIVER - Abstract
Different models of isolated and perfused livers and precision cut liver slices have been developed for studies on liver toxicology the past years. As most of these models were limited by nonphysiologic settings, a new model of normothermic hemoperfused isolated porcine slaughterhouse livers to examine hepatotoxicity was established encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. As model compound, the analgesic substance diclofenac was used and the effects of this drug on organ function parameters were compared to an untreated control group. Using an amount of 2,000 ml, the organs were perfused over 180 minutes, metabolically controlled via a dialysis and oxygenation system and various hematological and hepatic parameters were examined. In contrast to the untreated control organs, significant differences were found in the diclofenac group for parameters such as lactate, creatinine, ALT, bicarbonate, or bile flow. In summary, the presently established model of isolated hemoperfused slaughterhouse livers displays a useful new approach to assess hepatotoxicity of different substances on the organ level. As a major economic advantage in comparison to setups using laboratory animals, the new model can be run with blood and organs obtained from slaughterhouse animals. [ABSTRACT FROM AUTHOR]
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- 2002
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46. Identification and quantification of gold engineered nanomaterials and impaired fluid transfer across the rat placenta via ex vivo perfusion
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Laura Fabris, Brian Buckley, Michael Goedken, S. B. Fournier, Jeanine N D'Errico, Cathleen Doherty, Phoebe A. Stapleton, N. Renkel, and S. Kallontzi
- Subjects
0301 basic medicine ,Gold nanomaterials ,Placenta ,RM1-950 ,Umbilical cord ,Umbilical vein ,Article ,Andrology ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine.artery ,medicine ,ICP-MS ,Animals ,Uterine artery ,Pharmacology ,Fetus ,Chemistry ,Engineered nanomaterial ,Uterine horns ,Umbilical artery ,General Medicine ,Organ perfusion ,Nanostructures ,Perfusion ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Therapeutics. Pharmacology ,Gold ,Ex vivo - Abstract
Development and implementation of products incorporating nanoparticles are occurring at a rapid pace. These particles are widely utilized in domestic, occupational, and biomedical applications. Currently, it is unclear if pregnant women will be able to take advantage of the potential biomedical nanoproducts out of concerns associated with placental transfer and fetal interactions. We recently developed an ex vivo rat placental perfusion technique to allow for the evaluation of xenobiotic transfer and placental physiological perturbations. In this study, a segment of the uterine horn and associated placenta was isolated from pregnant (gestational day 20) Sprague-Dawley rats and placed into a modified pressure myography vessel chamber. The proximal and distal ends of the maternal uterine artery and the vessels of the umbilical cord were cannulated, secured, and perfused with physiological salt solution (PSS). The proximal uterine artery and umbilical artery were pressurized at 80 mmHg and 50 mmHg, respectively, to allow countercurrent flow through the placenta. After equilibration, a single 900 μL bolus dose of 20 nm gold engineered nanoparticles (Au-ENM) was introduced into the proximal maternal artery. Distal uterine and umbilical vein effluents were collected every 10 min for 180 min to measure placental fluid dynamics. The quantification of Au-ENM transfer was conducted via inductively coupled plasma mass spectrometry (ICP-MS). Overall, we were able to measure Au-ENM within uterine and umbilical effluent with 20 min of material infusion. This novel methodology may be widely incorporated into studies of pharmacology, toxicology, and placental physiology.
- Published
- 2019
47. Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation.
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Veloso-Giménez V, Escamilla R, Necuñir D, Corrales-Orovio R, Riveros S, Marino C, Ehrenfeld C, Guzmán CD, Boric MP, Rebolledo R, and Egaña JT
- Abstract
Oxygen is the key molecule for aerobic metabolism, but no animal cells can produce it, creating an extreme dependency on external supply. In contrast, microalgae are photosynthetic microorganisms, therefore, they are able to produce oxygen as plant cells do. As hypoxia is one of the main issues in organ transplantation, especially during preservation, the main goal of this work was to develop the first generation of perfusable photosynthetic solutions, exploring its feasibility for ex vivo organ preservation. Here, the microalgae Chlamydomonas reinhardtii was incorporated in a standard preservation solution, and key aspects such as alterations in cell size, oxygen production and survival were studied. Osmolarity and rheological features of the photosynthetic solution were comparable to human blood. In terms of functionality, the photosynthetic solution proved to be not harmful and to provide sufficient oxygen to support the metabolic requirement of zebrafish larvae and rat kidney slices. Thereafter, isolated porcine kidneys were perfused, and microalgae reached all renal vasculature, without inducing damage. After perfusion and flushing, no signs of tissue damage were detected, and recovered microalgae survived the process. Altogether, this work proposes the use of photosynthetic microorganisms as vascular oxygen factories to generate and deliver oxygen in isolated organs, representing a novel and promising strategy for organ preservation., Competing Interests: Author CG was employed by company Sky-Walker SpA. Competing Interests: JTE is CSO and co-founder of SymbiOx Inc., a start-up company that owns IP in the field of this work. Thanks to an R and D grant provided by the Chilean Ministry of Economics (CORFO), during the conduct of this project, DN, RE and RC-O were full-time employees of SymbiOx Inc. All other authors declare that they have no competing interests., (Copyright © 2021 Veloso-Giménez, Escamilla, Necuñir, Corrales-Orovio, Riveros, Marino, Ehrenfeld, Guzmán, Boric, Rebolledo and Egaña.)
- Published
- 2021
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48. Blood flow resistance during hemodilution: effect of plasma composition.
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Pries, Axel R, Secomb, Timothy W, Sperandio, Markus, and Gaehtgens, Peter
- Abstract
Objectives: To investigate the causes of wide variations in reported effects of hemodilution on flow resistance of vascular beds. Methods: (a) In a meta-analysis of 28 prior studies, resistance values at hematocrits of zero (R0) and 0.45 (R0.45) were derived. Study design characteristics (presence of vasodilatory reserve or leukocytes, species, tissue, hemodiluent) were tested by ANOVA for their relation to the ratio R0/R0.45. (b) Experiments were performed to determine flow resistance during hemodilution in the rat mesentery with (n = 8) and without (n = 11) pretreatment with heparinase, which modifies the endothelial glycocalyx. (c) A mathematical flow simulation for mesenteric microvascular networks was used to predict resistance effects of hemodilution and of a hypothetical layer on the endothelial surface. Results: (a) In prior studies using native plasma for hemodilution R0 averaged 59±8% of R0.45, while in studies using artificial solutions R0 averaged 32±12% of R0.45. The larger reduction of flow resistance upon dilution with artificial media is independent of viscosity and oncotic pressure. Other design characteristics did not show strong significant effects. (b) Present experiments showed large reductions of flow resistance with saline hemodilution which were nearly halved after heparinase pretreatment. (c) Resistance effects of hemodilution with plasma or after heparinase treatment agree with model predictions based on tube flow rheology of blood. The larger resistance effects of dilution with artificial media can be explained by the removal of an endothelial surface layer of ∼1.5 μm thickness. Conclusions: The results imply that changes of plasma composition, due to use of artificial infusion media, influence peripheral resistance and tissue perfusion. They are consistent with the hypothesis that interactions between endothelial glycocalyx structures and plasma components lead to formation of a thick layer at the endothelial surface which increases flow resistance. [ABSTRACT FROM PUBLISHER]
- Published
- 1998
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49. Heart transplant advances: Ex vivo organ-preservation systems.
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Bryner BS, Schroder JN, and Milano CA
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- 2021
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50. The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patients
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Can Ince, E. Christiaan Boerma, and Faculteit der Geneeskunde
- Subjects
Mean arterial pressure ,Critical Illness ,Vasodilator Agents ,Vasoactive ,Review ,Critical Care and Intensive Care Medicine ,Microcirculation ,Sepsis ,Vasomotor tone ,Oxygen Consumption ,Intensive care ,medicine ,Humans ,Vasoconstrictor Agents ,Septic shock ,business.industry ,Shock ,medicine.disease ,Organ perfusion ,Blood pressure ,Oxygenation ,Shock (circulatory) ,Anesthesia ,medicine.symptom ,business ,Perfusion - Abstract
Purpose The clinical use of vasoactive drugs is not only intended to improve systemic hemodynamic variables, but ultimately to attenuate derangements in organ perfusion and oxygenation during shock. This review aims (1) to discuss basic physiology with respect to manipulating vascular tone and its effect on the microcirculation, and (2) to provide an overview of available clinical data on the relation between vasoactive drugs and organ perfusion, with specific attention paid to recent developments that have enabled direct in vivo observation of the microcirculation and concepts that have originated from it. Methods A MedLine search was conducted for clinical articles in the English language over the last 15 years pertainig to shock, sepsis, organ failure, or critically ill patients in combination with vasoactive drugs and specific variables of organ perfusion/oxygenation (e.g., tonometry, indocyanine clearance, laser Doppler, and sidestream dark field imaging). Results Eighty original papers evaluating the specific relationship between organ perfusion/oxygenation and the use of vasoactive drugs were identified and are discussed in light of physiological theory of vasomotor tone. Conclusions Solid clinical data in support of the idea that increasing blood pressure in shock improves microcirculatory perfusion/oxygenation seem to be lacking, and such a concept might not be in line with physiological theory of microcirculation as a low-pressure vascular compartment. In septic shock no beneficial effect on microcirculatory perfusion above a mean arterial pressure of 65 mmHg has been reported, but a wide range in inter-individual effect seems to exist. Whether improvement of microcirculatory perfusion is associated with better patient outcome remains to be elucidated.
- Published
- 2010
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