5
Views
7
CrossRef citations to date
0
Altmetric
Original Article

Effect of the Endothelin Receptor Antagonist Bosentan on Postischemic Oxygen Supply of the Liver

, , , &
Pages 439-445 | Received 04 Jan 1996, Accepted 07 Jul 1996, Published online: 09 Jul 2009
 

Abstract

Endothelin evokes strong and longlasting constriction of postischemic sinusoids, leading to microcirculatory disturbances and local hypoxia, thereby causing liver damage. The aim of the study wus to avoid the constrictive response of sinusoids by blocking endothelin receptors. In an in vivo ischemia-reperfusion model (21 female Wistar rats, 250–300 g) with portal decompression by a splenocaval shunt, hepatic ischemia was induced for 30 min by cross clamping of the hepatoduodenal ligament. The endothelin receptor antagonist bosentan (10 mg/kg bw IV) was administered before ischemia. The effect of the receptor antagonist was assessed by serum levels of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) that were determined prior to ischemia, 2 and 6 h postoperatively. The local tissue pO2 was measured prior to inducing ischemia, 30 and 60 min after reperfusion. Application of 10 mg/kg bw endothelin receptor antagonist (ERA) intravenously did not influence the systemic blood pressure. The postischemic increase in serum ASAT and ALAT levels was diminished after receptor antagonist treatment (ASAT: p <. 05). Local postischemic hepatic tissue pO2 was significantly decreased to 45% of basal values after 30 min and to 54.8% after 60 min of reperfusion (p <.05). Application of ERA results in a significant increase in local tissue pO2 to 110.9% of basal values after 30 min and to 90.7% after 60 min of reperfusion (p <. 05). These data indicate that the endothelin receptor antagonist treatment results in a prevention of postischemic sinusoidal constriction avoiding hypoxia and leading to improved hepatocellular recovely

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.