Effect of the endothelin receptor antagonist bosentan on postischemic oxygen supply of the liver.
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 was 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 recovery.
Spiegel
H U
HU
Department of General Surgery-Surgical Research, Westfaelische Wilhelms-University, Muenster, Germany.
Uhlmann
D
D
Scommotau
S
S
Giersch
B
B
Sulkowski
U
U
D000818:Animals; D001794:Blood Pressure; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D005260:Female; D008099:Liver / Q000098:blood supply* / Q000601:surgery; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy*; D013449:Sulfonamides / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D000077300:Bosentan; D010100:Oxygen