Attenuation of proinflammatory gene expression and microcirculatory disturbances by endothelin A receptor blockade after orthotopic liver transplantation in pigs.

Background: Endothelin-1 (ET-1), a very potent mediator of vasoconstriction, leads to microcirculatory disturbances and release of proinflammatory cytokines under pathophysiologic conditions. Our aim was to evaluate the effect of a selective ET(A)-receptor antagonist (ET(A)-RA) on cold ischemia/reperfusion (I/R) injury in a pig model.

Methods: Twenty pigs revealed orthotopic liver transplantation.

Validation of large particle flow cytometry for the analysis and sorting of intact pancreatic islets.

Background: Accurate quantification of total islet yield is an essential step prior to transplantation and for research. The standard method of manually determining an islet equivalent (IEQ) count is subjective and prone to error. We evaluated Complex Object Parametric Analyzer and Sorter (COPAS) large particle flow cytometry for the determination of islet equivalent counts and purities of islet preparations.

Effects of ET(A) receptor antagonism on proinflammatory gene expression and microcirculation following hepatic ischemia/reperfusion.

Background: The objective of this study was to investigate the effect of a specific endothelin(A) receptor antagonist (ET(A)-RA) on mRNA expression of genes encoding vasoactive mediators and proinflammatory cytokines and on the microhemodynamics (assessed by measurement of laser Doppler flow and tissue blood gases) following complete vascular exclusion of the porcine liver.

Study Design: Sixteen adult German landrace pigs were subjected to 120 min of warm hepatic ischemia by total vascular exclusion. To avoid portal congestion, a passive porto-femoro/jugular bypass was implanted.

The endothelin/nitric oxide balance determines small-for-size liver injury after reduced-size rat liver transplantation.

Small-for-size (SFS) liver graft injury is probably related to microcirculatory disorders due to an imbalance of vasoconstricting, e.g. endothelin (ET)-1, and vasorelaxing mediators, e.

Changes of vasoregulatory gene expression following hepatic ischemia/reperfusion and treatment with endothelin-A receptor blockade.

The objective of this study was to investigate the effect of a specific endothelin-A receptor antagonist on mRNA expression of genes encoding vasoactive mediators and proinflammatory cytokines following complete vascular exclusion of the porcine liver. Fourteen adult German Landrace pigs were subjected to 120 minutes of warm hepatic ischemia by total vascular exclusion. The animals were divided into two groups: the control group received saline solution and the therapy group was given the selective endothelin-A receptor antagonist BSF 208075.

Amelioration of microcirculatory damage by an endothelin A receptor antagonist in a rat model of reversible acute liver failure.

Background/aims: Hepatocellular damage in acute liver failure (ALF) is aggravated by proinflammatory and cytotoxic mediators released from sinusoidal-lining cells. We studied a selective endothelin A receptor (ETAR) antagonist for its potential influence on the microcirculation in the setting of ALF.

Methods: Seventy Wistar rats were divided into five groups: (I) induction of ALF by a 70% liver resection combined with injection of 400 microg/kg endotoxin, (II) ALF treated with the ETAR antagonist LU 135252 (1 mg/kg b.

Improvement of postischemic hepatic microcirculation after endothelinA receptor blockade--endothelin antagonism influences platelet-endothelium interactions.

Endothelin (ET) contributes to disturbances of hepatic microcirculation after ischemia/reperfusion (I/R) by causing vasoconstriction and enhancing leukocyte- and platelet-endothelium interactions. The aim of this study was to investigate a possible protective role of a selective endothelin(A) receptor antagonist (ET(A)-RA) in this setting. In a rat model, warm ischemia of the left lateral liver lobe was induced for 90 minutes under intraperitoneal anesthesia with xylazine and ketamine.

Assessment of hepatic ischemia-reperfusion injury by simultaneous measurement of tissue pO2, pCO2, and pH.

Introduction: The objective of this study was to determine whether the simultaneous measurement of tissue pH, pCO(2), and pO(2) with a multiple-parameter fiberoptic sensor (Paratrend 7) can be used for continuous monitoring of hepatic microperfusion in a pig model of hepatic ischemia given endothelin(A) receptor antagonist (ET(A)-RA) or isotonic saline.

Methods: Fourteen anesthetized swine were subjected to 2 h of hepatic vascular exclusion. The animals were randomized into two groups: control group (n = 7, saline solution iv) and therapy group (n = 7, ET(A)-RA).

Endothelin(A) receptor blockade reduces ischemia/reperfusion injury in pig pancreas transplantation.

Objective: The effect of prophylactic administration of a selective endothelin(A) receptor antagonist (ET(A)-RA) on ischemia/reperfusion injury in an experimental model of graft pancreatitis after pancreas transplantation was evaluated.

Summary Background Data: It is well established that endothelin-1 (ET-1), a powerful vasoconstrictor, plays an important role in the development of pancreatitis. Recent studies have shown a beneficial effect of endothelin receptor antagonists in the therapy for experimental pancreatitis.

Endothelin A receptor blockade reduces hepatic ischemia/reperfusion injury after warm ischemia in a pig model.

It is well established that endothelin-1 (ET-1) is a very potent mediator of vasoconstriction that leads to microcirculatory disturbances. The aim of the study was to evaluate the effect of a selective endothelin A receptor antagonist on severe ischemia/reperfusion injury in a pig model. Fourteen pigs were subjected to 120 minutes of complete vascular exclusion of the liver with a passive bypass.

Comparison of Celsior and UW solution in experimental pancreas preservation.

Background: The University of Wisconsin solution (UW) is the gold standard for pancreas preservation. Celsior (CEL) was formulated specifically for heart preservation. Recently, experimental and clinical experience has been reported on the application of CEL to abdominal organs.