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Background: ModulHeart (Puzzle Medical Devices Inc) is a novel percutaneous flow entrainment pump anchored in the descending aorta. The current study evaluates the hemodynamic effect of ModulHeart support and its impact on cerebral, myocardial, and renal blood flow. Methods: ModulHeart was implanted in the descending aorta of four healthy calves. A ramp protocol (2000 RPM increments) was performed with the pump operating at five different speeds from 14 000 to 22 000 RPM. For each speed, pressures proximal and distal to the pump, and right heart catheterization measurements were recorded. Stable‐isotope labeled microspheres were injected in the left ventricle to evaluate organ perfusion. Results: Thermodilution cardiac output increased by 23% at 22 000 RPM. Greater pump speeds resulted in greater pump gradients, up to 10 mm Hg in mean arterial pressure at 22 000 RPM, without significant reduction of proximal perfusion pressures. Arterial pulse pressure remained stable at all speeds. ModulHeart was not associated with a reduction in cerebral or myocardial blood flow at any speed. Renal cortical and medullary blood flow increased by up to 50% and 40%, respectively. Conclusion: The ModulHeart device implanted in the descending aorta of healthy calves resulted in significant arterial pressure gradients and preserved pulse pressure. Greater pump speeds translated into greater increases in renal blood flow, with no decrease in cerebral or myocardial perfusion. [ABSTRACT FROM AUTHOR]

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]

To alleviate the persistent shortage of donor livers, high‐risk liver grafts are increasingly being considered for liver transplantation. Conventional preservation with static cold storage falls short in protecting these high‐risk livers from ischemia–reperfusion injury, as evident from higher rates of post‐transplant complications such as early allograft dysfunction and ischemic cholangiopathy. Moreover, static cold storage does not allow for a functional assessment of the liver prior to transplantation. To overcome these limitations, dynamic strategies of liver preservation have been proposed, designed to provide a protective effect while allowing pre‐transplant functional assessment. In this review, we discuss how different dynamic preservation strategies exert their effects, where we stand in assessing liver function and what challenges are lying ahead. [ABSTRACT FROM AUTHOR]

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]

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]

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. 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. 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. 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 groups and to provide a valid comparator cohort for future clinical trials. 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 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort. [Display omitted] • Benchmarking criteria were developed based on more than 2,000 DCD liver transplantations performed in 17 centres worldwide. • Benchmark cut-off target values were established for the most relevant clinical parameters. • Machine perfusion technology improved outcomes of a high-risk DCD sub-cohort, leading to similar results as in the benchmark population. • This benchmarking tool can serve as a baseline for future trials in the field. [ABSTRACT FROM AUTHOR]

BACKGROUND: The cold ischemia –reperfusion injury may lead to microcirculatory disturbances, hepatocellular swelling, inflammation, and organ dysfunction. Nicorandil is an anti-ischemic, ATP-sensitive potassium (KATP) channel opener drug and has proved its effectiveness against hepatic Ischemia/Reperfusion (I/R) injury. OBJECTIVE: This study aimed to investigate the effect of Nicorandil on mitochondrial apoptosis, oxidative stress, inflammation, histopathological changes, and cold ischemic tolerance of the liver in an ex vivo experimental isolated-organ-perfusion model. METHODS: We used an ex vivo isolated rat liver perfusion system for this study. The grafts were retrieved from male Wistar rats (n = 5 in each), preserved in cold storage (CS) for 2 or 4 hours (group 1, 2), or perfused for 2 or 4 hours (group 3, 4) immediately after removal with Krebs Henseleit Buffer (KHB) solution or Nicorandil containing KHB solution under subnormothermic (22–25°C) conditions (group 5, 6). After 15 minutes incubation at room temperature, the livers were reperfused with acellular, oxygenated solution under normothermic condition for 60 minutes. RESULTS: In the Nicorandil perfused groups, significantly decreased liver enzymes, GLDH, TNF-alpha, and IL-1ß were measured from the perfusate. Antioxidant enzymactivity was higher in the perfused groups. Histopathological examination showed ameliorated tissue deterioration, preserved parenchymal structure, decreased apoptosis, and increased Bcl-2 activity in the Nicorandil perfused groups. CONCLUSIONS: Perfusion with Nicorandil containing KHB solution may increase cold ischemic tolerance of the liver via mitochondrial protection which can be a potential therapeutic target to improve graft survival during transplantation. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

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]

Injection of fluorescence-labelled microspheres (FMs) in pigs allows only the postmortem determination of organ perfusion. Colour duplex ultrasound (CDU) and contrast-enhanced ultrasound were established as techniques for real-time imaging of tissue perfusion in a porcine haemorrhagic shock model. Haemorrhagic shock was provoked in nine domestic pigs by taking at least 15% of the calculated blood volume. Ultrasound examinations were performed with a Hitachi HI VISION Ascendus. SonoVue was injected for contrast-enhanced ultrasound. Monitoring of the resistive index and time-to-peak ratio enabled quantification of tissue perfusion in vivo during the entire study, allowing real-time differentiation of animals with systemic shock versus failing shock effect. Postmortem analyses of injected FMs confirmed the sonographic in vivo results. Determination of the resistive index and time-to-peak ratio by CDU and contrast-enhanced ultrasound allowed real-time monitoring of tissue perfusion. Effects of haemorrhagic shock and therapeutic approaches related to organ perfusion can be observed live and in vivo. [ABSTRACT FROM AUTHOR]

Background: The isolated heart apparatus is over 100 years old, but remains a useful research tool today. While designs of many large animal systems have been described in the literature, trouble-shooting and refining such a model to yield a stable, workable system has not been previously described. This paper outlines the issues, in tabular form, that our group encountered in developing our own porcine isolated heart rig with the aim of assisting other workers in the field planning similar work. The paper also highlights some of the modern applications of the isolated heart apparatus. Methods Landrace pigs (50-80 kg) were used in a pilot project to develop the model. The model was then used in a study examining the effects of various cardioplegic solutions on function after reanimation of porcine hearts. During the two projects, non-protocol issues were documented as well as their solutions. These were aggregated in this paper. Results: Issues faced by the group without explicit literature solutions included pig size selection, animal acclimatisation, porcine transoesophageal echocardiography, cannulation and phlebotomy for cross-clamping, cardioplegia delivery, heart suspension and rig tuning. Conclusion: Prior recognition of issues and possible solutions faced by workers establishing a porcine isolated heart system will speed progress towards a useable system for research. The isolated heart apparatus remains applicable in transplant, ischaemia reperfusion, heart failure and organ preservation research. [ABSTRACT FROM AUTHOR]

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]

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]

Background Efficient and effective perfusion during organ procurement is required for the best prevention of donor organ injury preceding transplantation. However, current organ preservation solutions, including hydroxyethyl starch (HES)–based University of Wisconsin (UW) solution, do not always yield the best outcomes. Our previous study demonstrated that replacing HES with hyperbranched polyglycerol (HPG) reduced donor heart injury during cold storage. The current research was designed to examine the advantages of HPG-based solution for cold kidney perfusion. Methods Perfusion efficiency of HPG versus UW solution was tested using mouse kidneys at 4°C. The blood washout was evaluated by using a semiquantitative scoring system and tissue damage by histologic analysis. The interaction of HPG or UW solution with human red blood cells (RBCs) was examined by measuring RBC sedimentation and aggregation. Results The lower viscosity of HPG solution was correlated with faster and more efficient perfusion through donor kidneys as compared with UW. HPG solution was also more effective than UW in removing RBCs from the kidney and was associated with less tissue damage to donor kidneys. In vitro UW solution caused significant RBC sedimentation and hyperaggregation, whereas HPG showed minimal impact on RBC sedimentation and prevented RBC aggregation. Conclusions This experimental study demonstrated that compared with UW, HPG solution was more efficient and effective in the removal of the blood from donor kidneys and offered better protection from donor tissue damage, suggesting that the HPG solution is a promising candidate to supplant standard UW solution for donor kidney perfusion in transplantation. [ABSTRACT FROM AUTHOR]

Background Ex vivo lung perfusion with acellular solutions is an established technique for assessing marginal donor lungs. We evaluated the utility of a blood-based lung preservation fluid as an alternative perfusate. Methods Donor lungs from 50-kg donation after cardiac death pigs (n = 24) were randomized into 3 groups: acellular, commercial blood-based, and Papworth-Blood. Physiologic function was evaluated using conventional markers of pulmonary vascular resistance, pulmonary compliance, lactate excretion, partial pressure of oxygen/fraction of inspired oxygen, and wet-to-dry ratios. The immunologic profile was assessed by fluorescence-activated cell sorting analysis of bronchoalveolar lavage and cells entrapped in the leucocyte filter. Cytokines were quantified using a commercial platform. Results No significant difference was noted in pulmonary vascular resistance ( p = 0.26), compliance ( p = 0.12), partial pressure of oxygen/fraction of inspired oxygen ( p = 0.06) and wet-to-dry ratios ( p = 0.26) between groups. There was no difference between the percentages of lymphocytes ( p = 0.51), macrophages ( p = 0.87), monocytes ( p = 0.68), and dendritic cells ( p = 0.65) in the leukocyte filters. Interleukin (IL)-1β ( p = 0.36), IL-6 ( p = 0.08), IL-8 ( p = 0.64), and IL-18 ( p = 0.14) were elevated in all groups. In bronchoalveolar lavage, IL-8 was significantly higher in the acellular group ( p = 0.04). Electron microscopy cell characteristics were similar among the groups. Conclusions This study demonstrated no significant difference in the physiologic, immunologic, or ultrastructural parameters between lungs perfused with cellular or acellular solutions. The Papworth-Blood solution is a potential alternative perfusate for ex vivo lung perfusion. [ABSTRACT FROM AUTHOR]

Raman spectroscopy was applied in this research to monitor the overall health and degradation of porcine livers perfused ex vivo using the VasoWaveW® perfusion system. A novel Raman-based diagnostic analysis was developed that enables near real-time and label-free monitoring of organ health during ex vivo perfusion designed to extend the useful life of the organ for transplantation. Multivariate statistical analysis of Raman spectra of organ perfusate fluid, using a combination of principal component analysis and linear discriminant analysis, proved to be an effective technique to assess the degradation properties of the livers. Three livers (with replicates) were perfused ex vivo under different pressures and temperatures and were compared with a 24-h time-course. Results indicated that perfusion pressure was a more significant factor in organ degradation than was temperature. In addition, a non-linear degradation profile was identified for all three perfused livers, and this profile was different for individual livers, demonstrating the time-dependent transition from its initial 'healthy' state towards a more 'unhealthy' degenerative state at 24 h. The Raman spectroscopy-based approach described here has potential applications in perfusion and diagnostic instrumentation that can be used in near real-time during organ transit and in operating rooms to help identify appropriately healthy organs for transplantation. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to assess the incidence of sublingual microcirculatory flow alterations, according to a predefined arbitrary cutoff value, in patients with 'clinical signs of impaired organ perfusion'. Secondary endpoints were the changes in microvascular flow index (MFI), 'clinical signs of impaired organ perfusion', and stroke volume (SV) after fluid administration, and the differences between groups. Methods: Prospective, single-center, observational study in a 22-bed mixed intensive care unit (ICU). Patients ≥18 years with invasive hemodynamic monitoring and 'clinical signs of impaired organ perfusion' as the principal reason for fluid administration were included. Before and after fluid challenge, systemic hemodynamics and direct in vivo observation of the sublingual microcirculation with sidestream dark-field imaging were obtained. Microvascular flow index (MFI) <2.6 was predefined as abnormal. Results: N = 50. At baseline, MFI <2.6 was present in 66 % of the patients. In these patients, MFI increased from 2.3 (2-2.5) at baseline to 2.5 (2.1-2.8) after fluid challenge ( p = 0.003). This was accompanied by a reduction in the number of 'clinical signs of impaired organ perfusion' from 2 (1-2) to 1 (0-2) ( p < 0.001). However, in patients with MFI >2.6 at baseline, MFI and clinical signs changed insignificantly [2.8 (2.8-2.9) versus 2.8 (2.7-3), p = 0.45, respectively, 1 (1-2) versus 1 (1-2), p < 0.32]. These changes were not restricted to patients with a rise in SV ≥10 %. Conclusions: These data add to the understanding that noninvasive assessment of microvascular blood flow may help to identify patients eligible for fluid therapy, and to evaluate its effect. [ABSTRACT FROM AUTHOR]

Purpose: A fall in tissue oxygen tension (tPO) is an early indicator of organ hypoxia in both patients and animal models. We previously demonstrated the utility of bladder tPO in various rodent shock models. As a prelude to clinical testing, we aimed to provide further validation of bladder tPO monitoring in a large animal model undergoing a range of cardiorespiratory insults and vasoactive drug interventions. Methods: Anaesthetized, mechanically ventilated, instrumented female pigs ( n = 8) were subjected to a range of short-term cardiorespiratory (changes in inspired oxygen concentration (FiO), haemorrhage, positive end-expiratory pressure) and pharmacologic (inotrope, pressor) challenges. Global haemodynamics, arterial and pulmonary blood gases and bladder tPO were measured before and after each challenge. Results: Bladder tPO values fell in line with increasing degrees of hypoxaemia and haemorrhage, and were restored during resuscitation. These changes often preceded those seen in global haemodynamics, arterial base excess and lactate. The rise in bladder tPO with hyperoxia, performed as an oxygen challenge test, was incrementally blunted by progressive haemorrhage. Dobutamine and norepinephrine both increased cardiac output and global O delivery, but had no effect on bladder tPO or lactataemia in these healthy pigs. Conclusions: In this pig model bladder tPO provides a sensitive indicator of organ hypoxia compared to traditional biochemical markers during various cardiorespiratory challenges. This technique offers a potentially useful tool for clinical monitoring. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: There is a need for reliable continuous monitoring of abdominal organ oxygen saturation (SpO2). Splanchnic ischaemia may ultimately lead to cellular hypoxia and necrosis and contribute to the development of multiple organ failure and increased mortality. A reflectance electro-optical photoplethysmographic (PPG) probe and signal processing system were developed. Satisfactory PPG signals from abdominal organs (bowel, liver and kidney) and the finger were obtained from 12 anaesthetised patients. There were no statistically significant differences between the average PPG amplitudes recorded from the abdominal organs and those obtained simultaneously from the finger. These observations suggest that pulse oximetry can be a valid monitoring technique for abdominal organs such as the bowel, liver and kidney. [Copyright &y& Elsevier]

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]

1. Poor perfusion of the kidneys and gut, and associated functional impairment, are major problems in the first days of life in very preterm infants. These complications can be associated with a substantial mortality and further problems such as reduced kidney growth and chronic renal problems in later childhood. 2. There is very little information, and consequently considerable debate, about how or even whether to improve perfusion of the vital organs of this most vulnerable group of babies. Current treatments simply do not consistently improve babies’ perfusion generally or kidney and gut perfusion and function in particular. 3. In this review we critically examine clinical and experimental evidence that suggests that exposure to low oxygen levels before and during birth may be a significant contributor to impaired systemic perfusion, and highlight areas requiring further research. 4. This knowledge is essential to develop and refine ways of improving perfusion of the kidneys and other vital organs in premature babies. [ABSTRACT FROM AUTHOR]

Baicu SC, Simmons PM, Campbell LH, Taylor MJ, Brockbank KGM. Interstitial fluid analysis for assessment of organ function. Clin Transplant 2004: 18 (Suppl. 12): 16–21. © Blackwell Munksgaard, 2004 Evaluation methods are required for non-heart-beating donor (NHBD) kidneys to ensure the success of transplantation. In this study, the microdialysis technique was employed for the ex-vivo assessment of hypothermically preserved NHBD kidney function. Microdialysis probes were placed in the renal cortex of 2 h warm ischaemic porcine kidneys to monitor interstitial pyruvate dynamics during hypothermic machine perfusion with perfusate containing 29.4 mM fructose-1,6-diphosphate (FDP). The presence of exogenous FDP in the perfusate induced no changes in the renal flow rate and vascular resistance, renal artery effluent biochemistry, or pyruvate concentration relative to untreated control kidneys. Significant increases in pyruvate production ( P < 0.05), however, were observed after 12 h of perfusion in the interstitial fluid of FDP-treated kidneys relative to control kidneys. After 24 h of perfusion, interstitial fluid concentrations of pyruvate were 149.1 ± 58.4 vs. 55.6 ± 17.9 µM ( P < 0.05) in the FDP and control group, respectively. The microdialysis probe collected the interstitial fluid directly from the cellular sites of metabolic and synthetic activity, where perfusate dilution was minimal. Consequently, the biochemical changes induced by the organ metabolic activity were detected only at the interstitial level, in the microdialysates. Interstitial fluid pyruvate may be a good indicator of kidney function. The addition of FDP to the perfusion solution during ischaemic kidney preservation resulted in enhanced pyruvate production in the extracellular space, indirectly reflecting an increase in anaerobic ATP production. The pyruvate will be transformed during organ reperfusion into acetyl Co-A enzyme allowing an immediate start of aerobic metabolism. This in turn can increase the amount of ATP available to the cells and may help prevent reperfusion injury upon transplantation. [ABSTRACT FROM AUTHOR]

Purpose of the study: To investigate the haemodynamic properties of a direct endovascular aortic shunt to maintain distal aortic perfusion as an alternative of a distal shunt (left-left-, Gott shunt) in thoracic aortic aneurysm repair.Methods: A shunt was developed and tested in an in vitro model which should be capable of transporting a flow of 3–4 L/min with a decrease in blood pressure < 20 mmHg. Thereupon the shunt was tested in an in vivo experiment in six pigs to assess the possibility of its use with normal distal blood pressure. The shunt was inserted in the thoracic aorta and stayed in place for 1.5 h. Parameters were measured at six time intervals to assess organ perfusion, -function, cardiac output, proximal- and distal blood pressure and aortic- and shunt flow.Principle findings: The mean blood flow through the shunt was 2.5 L/min. The difference of the mean blood pressure over the shunt was on average 14.20 mmHg. Parameters for coagulation disturbance and organ ischaemia were tested. The decrease in mean trombocyt count was 299–158 (p<0.02). The venous lactate and the venous mesenteric lactate as parameters for intestinal ischemia did not increase significantly. No significant changes occurred in angiotensin II levels. Pulsatile flow was maintained but significantly suppressed (60%) distal from the shunt. The clamp time needed to insert the shunt and the venous mesenteric lactate, as well as the venous lactate, showed high correlation, rs = 0.9 (p<0.05) and rs = 0.94 (p<0.01). This also accounted for the 2nd clamp time, both rs = 0.95 (p<0.05).Conclusion: The shunt is capable of transporting a blood flow of 2–4 L/min with an acceptable decrease in distal blood pressure. However, the time, needed to insert the shunt, was significantly associated with parameters of organ ischaemia. [Copyright &y& Elsevier]

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]

Background. The optimal method for preserving livers from non-heart-beating donors (NHBD) is still unknown. We compared the Celsior solution, a new extracellular-type, low-potassium, low-viscosity preservation solution, with the University of Wisconsin (UW) solution in a canine orthotopic liver transplantation from NHBD.Materials and methods. Fourteen adult mongrel dogs, weighing 9 to 17 kg, were divided into two groups: the Celsior or the UW group (n = 7 each). The thoracic descending aorta and supradiaphragmatic inferior vena cava were cross-clamped for 20 min to induce warm ischemia as a NHBD model. The liver was flushed with the respective cold preservation solution and then stored at 4°C for 4 h. The grafts were transplanted using the piggy-back technique under portal decompression by leaving the native right lobe as a temporary shunt.Results. The duration of liver flushing out (min) was shorter (P < 0.05), and the serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase, lactate, and α-glutathione S-transferase concentrations 2 and 6 h after reperfusion of the graft (RPF) were lower (P < 0.05) in the Celsior group than in the UW group. Hepatic tissue blood flow (HTBF) did not deteriorate as much (P < 0.05) in the Celsior group. The serum endothelin-1 level was lower (P < 0.05) in the Celsior group 2 h after RPF. Histopathology of liver specimens revealed portal congestion and hepatocyte necrosis with neutrophil infiltration in the UW group, while these findings were mild in the Celsior group.Conclusions. The Celsior solution improves vascular endothelial injury in livers from NHBDs and may have advantages in graft flush and preservation of grafts from NHBDs. [Copyright &y& Elsevier]

Analyzes the phenomenon of deterministic chaos in heterogeneity of cardiac perfusion. Observation of heterogeneity of organ perfusion as a necessary adaptation to heterogeneous metabolism; Question of fractal geometry being an expression of deterministic chaos in myocardial perfusion; Discovery of chaotic properties in distribution of myocardial perfusion.

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. [ABSTRACT FROM AUTHOR]

Abstract: Research of the distributed artificial heart is important not only to acquire the means of individual organ perfusion but also to clarify the characteristics of the organ and the mechanism of blood distribution. To investigate the distributed artificial heart, the miniature undulation pump was developed. The outer diameter and the thickness of the developed pump were 38 mm and 11 mm, respectively. The priming volume of the pump was 3.2 ml. The total size including the motor unit was 38 mm in diameter and 32 mm in length. The total weight was 67.5 g. The total volume was 27.5 ml. The pump was driven with pulse width modulation by using a 1 chip motor controller. More than 5 L/min of continuous output could be obtained. The results showed that the developed miniature undulation pump system had enough performance for individual organ perfusion. [ABSTRACT FROM AUTHOR]

• Morphological barriers remain intact using our ex vivo placental perfusion technique. • Gold nanoparticles can translocate across the placenta within 20 min of material infusion. • Nanoparticle infusion can impair fluid flow from the maternal to fetal compartment. 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. [ABSTRACT FROM AUTHOR]