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Prevention of SARS-CoV-2 entry into cells through the modulation of viral host receptors, such as ACE2, could represent a new chemoprophylactic and therapeutic approach for COVID- 19 complementing vaccination. However, the mechanisms controlling ACE2 expression remain elusive, partly due to low ACE2 levels in experimental models. To address this challenge, I use biliary epithelial cell (cholangiocyte), one of the cell types with the highest ACE2 levels, to dissect the molecular mechanisms controlling ACE2 expression. I identify the farnesoid X receptor (FXR) as a direct regulator of ACE2 transcription in multiple COVID19- affected tissues, including the gastrointestinal and respiratory systems. I use this knowledge to optimise current experimental models for SARS-CoV-2 infection and I demonstrate that reduction of FXR signalling, with the over-the-counter compound z-guggulsterone (ZGG) and the off-patent drug ursodeoxycholic acid (UDCA), downregulates ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. I also show that UDCA-mediated ACE2 downregulation reduces susceptibility to SARS-CoV- 2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. I then illustrate that UDCA reduces ACE2 expression in the nasal epithelium in humans. Finally, I present a retrospective analysis using an independent patient cohort which identify a correlation between UDCA treatment and positive clinical outcomes following SARS-CoV-2 infection, including hospitalisation, ICU admission and death using retrospective COVID-19 registry data, and confirm these findings in a second independent cohort of liver transplant recipients. In conclusion, with the work described in this dissertation I identify a novel function of FXR in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, thereby paving the road for future clinical trials.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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.

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.

The reporting of infection/sepsis in chemo/radiation-treated head and neck cancer patients is sparse and the problem is underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of infections and sepsis. The Delphi appropriateness method was used for this consensus. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. The paper contains seven clusters of statements about the clinical definition and management of infections and sepsis in head and neck cancer patients, which had a consensus. Furthermore, it offers a review of recent literature in these topics. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Background: The aim of this study was to compare pre-arrest and post-resuscitation organ perfusion values and to investigate whether, during the post-resuscitation phase, administration of the angiotensin II antagonist telmisartan (TELM) 10 min after restoration of spontaneous circulation (ROSC) could improve organ flow in comparison to placebo. Results: Five minutes after ROSC in the TELM group, blood flow in the cortex and myocardium increased to 583% (P < 0.05) and 137% (not significant), respectively, whereas blood flow of the colon, stomach and pancreas decreased to 50% (P < 0.05), 28% (P < 0.05) and 19% (P < 0.05) of pre-arrest values, respectively. At 90 min after ROSC, pre-arrest perfusion values both in non-splanchnic and splanchnic organs were achieved. At no point in time were there significant differences between the two groups with respect to organ blood flow or speed of recovery of organ perfusion. Conclusions: During the post-resuscitation phase, organ blood flow is characterized by the coincidence of increased cerebral and myocardial blood flow and decreased intestinal blood flow. Administration of TELM 10 min after ROSC did not improve the recovery of organ perfusion.

Cardiac surgery in children has markedly advanced and is a mainstay for the treatment of serious congenital cardiac malformations. Because the heart, great vessels, and total blood volume are much smaller in children than in adults, the cardiopulmonary bypass procedure is challenging with respect

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 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

We describe a cost-effective, reproducible circuit in a porcine, ex vivo, continuous warm-blood, bi-ventricular, working heart model that has future possibilities for pre-transplant assessment of marginal hearts donated from brain stem dead donors and hearts donated after circulatory determination of death (DCDD). In five consecutive experiments over five days, pressure volume loops were performed. During working mode, the left ventricular end systolic pressure volume relationship (LV ESPVR) was 23.1±11.1 mmHg/ml and the LV preload recruitable stroke work (PRSW) was 67.8±7.2. (Standard PVAN analysis software) (Millar Instruments, Houston, TX, USA) All five hearts were perfused for 219±64 minutes and regained normal cardiac function on the perfusion system.They displayed a significant upward and leftward shift of the end systolic pressure volume relationship, a significant increase in preload recruitable stroke work and minimal stiffness. These hearts could potentially be considered for transplantation. The circuit was effective during reperfusion and working modes whilst proving to be successful in maintaining cardiac function in excess of four hours. Using an autologous prime of approximately 20% haematocrit (Hct), electrolytes and blood gases were easy to control within this period using standard perfusion techniques.

Aus vielen experimentellen und klinischen Studien geht hervor, dass ein Kapnoperitoneum zu charakteristischen Kreislaufveränderungen führt. Danach kommt es durch die Insufflation eines Gases in die Peritonealhöhle zu einer Erhöhung des intraperitonealen Druckes und zu einer Zunahme sowohl des peripheren venösen Druckes als auch des intrathorakalen Druckes. Insgesamt nimmt der Druckgradient zwischen diesen beiden Drücken ab. Als Folge wird der venöse Rückstrom zum Herzen reduziert, wodurch wiederum das Blutangebot für das Herz, welches die kardiale Vorlast wesentlich bestimmt, vermindert wird. Konsekutiv führt das letztlich zu einer Abnahme des Herzschlag- und des Herzminutenvolumens. Das verminderte Herzschlagvolumen wird von den arteriellen Barorezeptoren registriert, wodurch eine Stimulation des Sympathikus ausgelöst wird. Als Kompensationsmechanismus steigen die Herzfrequenz, in vielen Studien der mittlere arterielle Druck und der systemische Gefäßwiderstand. Als hormonelle Regulation wird Vasopressin ausgeschüttet. Der Anstieg dieser Drücke bedeutet eine Zunahme der kardialen Nachlast, was die kardiale Belastung weiter erhöht. Am gesunden Herzen wird die myokardiale Kontraktilität durch das Kapnoperitoneum nicht beeinflusst. An einem komplexen Tiermodell an 43 Läuferschweinen sollte überprüft werden, ob eine gezielte Erhöhung der kardialen Vorlast durch kolloidale Volumenersatzmittel, eine partielle Blockade der sympathikotonen Reaktionen durch den selektiven ß-Blocker Esmolol oder eine gezielte Senkung der kardialen Nachlast durch den Vasodilatator Nitroprussidnatrium geeignet sind, die negativen Auswirkungen des Kapnoperitoneums zu vermindern und die Herz-Kreislauffunktion bei laparoskopischen Operationen zu verbessern. Weil bekannt ist, dass die Körperposition eine wichtige Rolle bei der Ausprägung der physiologischen Veränderungen spielt, sollten die Tiere in Gruppen entweder in Horizontal-, Kopfhoch- oder Kopftieflage untersucht werden. Das ist von besonderer Bedeutung, weil viele laparoskopische Operationen zur Optimierung der Übersicht im Operationsgebiet eine Modifikation der Körperposition erfordern. Oberbaucheingriffe wie die Cholecystektomie werden vornehmlich in Kopfhochlage durchgeführt, während gynäkologische Laparoskopien in Kopftieflage stattfinden. Zur Vermeidung einer Hypovolämie erhielten die Tiere vor Beginn der Messungen 1l kristalloide Infusion. Die Untersuchungen ergaben, dass unter diesen Bedingungen ein Kapnoperitoneum von 14 mm Hg in Horizontallage ohne wesentliche Veränderungen der Herz- Kreislaufparameter toleriert wurde. Lediglich in Kopftief- und in Kopfhochlage war mit dem Intrathorakalen Blutvolumen ein wesentlicher Parameter der kardialen Vorlast vermindert und die Herzauswurfleistung mit dem Herzschlag- und Herzminutenvolumen reduziert, während die kardiale Nachlast mit dem peripheren systemischen Gefäßwiederstand erhöht war und die myokardiale Kontraktilität unverändert blieb. Damit kommt dem intrathorakalen Blutvolumen eine entscheidende Bedeutung zu. Eine Erhöhung des intrathorakalen Blutvolumens und damit der kardialen Vorlast verbesserte die Herzkreislauffunktion während des Kapnoperitoneums in allen Körperpositionen deutlich. Das äußerte sich in einer Steigerung des mittleren arteriellen Druckes, der im Normbereich blieb, einer Abnahme des systemischen Gefäßwiderstandes und einem Anstieg der Herzauswurfleistung. Die Esmolomedikation beeinträchtigte die Herzkreislauffunktion während des Kapnoperitoneums, indem sie die myokardiale Kontraktilität verschlechterte und die Herzfrequenz senkte mit der Folge, dass das Herzminutenvolumen abnahm. Die Senkung des mittleren arteriellen Druckes durch Nitroprussidnatrium verschlechterte ebenfalls in einigen Körperpositionen die myokardiale Kontraktilität und das Herzschlag- sowie das Herzminutenvolumen. Die beiden letztgenannten Konzepte können somit nicht generell zur Therapie hämodynamischer Effekte eines Kapnoperitoneums empfohlen werden. Entscheidende Bedeutung kommt einer Optimierung des intravasalen Volumens zu. Die Pfortader- und Nierendurchblutung wurden in diesem Modell durch das Kapnoperitoneum in keiner Körperposition relevant beeinträchtigt. Auch in der Literatur findet sich kein Hinweis auf eine durch ein Kapnoperitoneum induzierte dauerhafte Funktionsstörung von Leber oder Niere., A capnoperitoneum increases peripheral venous resistance as well as intrathoracic pressure thus compromising venous blood return to the heart which is determinded by the pressure gradient between peripheral and central venous pressure. With a decreased cardiac preload cardiac stroke volume and cardiac output are reduced. The reduction in stroke volume induces changes in the carotidal sinus activity followed by an increased sympathetic nerve activity. These effects were often expressed by an increased heart rate, mean arterial pressure, or peripheral systemic resistance. As a hormonal reaction to theses changes vasopressin release increases further elevating cardiac afterload. Changes of cardiac contractility were not described during capnoperitoneum. In a procine trial using 43 piglets the questions should be answered if an increase of cardiac preload by infusion of colloidal fluids, a partial blockade of sympathetic receptors by esmolol, or a reduction of the cardiac afterload by infusion of the vasodilatator nitroprussidnatrium can minimize hemodynamic changes during capnoperitoneum. Because the body position is known to influence hemodynamic parameters and has to be varied during laparoscopic procedures pigs were divided into three groups representing head-up, head-down, and supine position. To avoid hypovolemia before the measurements the animals received 1L cristal solutions intravenously before the beginning of the experiment. In supine position the animals tolerated a capnoperitoneum of 14 mm Hg without changes of hemodynamic parameters. In head-up as well as in head-down position the intrathoracic blood volume decraesed followed by a reduction of stroke volume and cardiac output and an increase of peripheral systemic resistance. Cardiac contractility remained unchanged during all positions. The increase of intrathoracic blood volume by colloidal infusion improved hemodynamic parameters during all body positions. Mean arterial pressure increasesd to normal ranges while the peripheral systemic resistance decreased and the cardiac output increased. The medication of esmolol had negative effects on hemodynamic function during capnoperitoneum because heart rate and myocardial contractility as well as cardiac output decreased. Medication of Nitroprussidnatrium during capnoperitoneum was also shown to partly compromise myocardial contractility and stroke volume as well as cardiac output so that both therapeutical concepts, medication of esmolol and nitroprussidnatrium failed to improve hemodynamic function during capnoperitoneum. Optimizing intravascular volume and cardiac preload is of major importance to avoid hemodynamic side effects of capnoperitoneum. The perfusion of the portal vein as well as the renal artery were not influenced in none position during a capnoperitoneum of 14 mm Hg in this trial. However, the review of the literature did not indicate any prolonged influences on hepatic or renal function induced by capnoperitoneum of pressures around 14 mm Hg.

Objectives: To evaluate the possible prevention of renal and intestinal ischaemia during surgery of thoracoabdominal aortic aneurysms (TAAA) by use of retrograde and selective organ perfusion. Design: Prospective study. Materials: Thirty-three consecutive patients underwent TAAA repair, six of whom had a previous type B dissection: 14 patients (35%) had type I TAAA, 12 patients type II (32%), three patients type III (15%) and four patients type IV (18%). Mean age was 61 years (range 22–84 years). Methods: In patients with type I TAAA, retrograde aortic perfusion was performed by means of a left atrium femoral artery bypass or partial cardiopulmonary bypass. In type II, III and IV the same procedure was performed; however, following cross-clamping and opening of the abdominal aorta, the coeliac trunc, superior mesenteric and both renal arteries were selectively perfused with four Pruitt-catheters (9 Fr.), connected as an octopus to the extracorporal circulation. Results: All patients survived the surgical procedure. The minimal volume flow through each octopus catheter was 60 ml/min. Urine output was uninterrupted in all patients, irrespective of the aortic cross-clamp time. Only one patient (3%), who already had renal insufficiency, developed renal failure. Total in-hospital mortality was 15%, paraplegia occurred in 12%. Conclusion: Retrograde aortic and selective organ perfusion is a safe technique and can prevent ischaemic renal and intestinal damage during cross-clamping of the aorta in thoracoabdominal aneurysm surgery.

Department of Anesthesiology, North Medical center, Kyoto Prefectural University of Medicine