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  • Title: Endothelin-A receptor blockade improves postischemic hepatic microhemodynamics.
    Author: Uhlmann D, Glasser S, Lauer H, Ludwig S, Gaebel G, Serr F, Hauss J, Witzigmann H.
    Journal: J Cardiovasc Pharmacol; 2004 Nov; 44 Suppl 1():S103-4. PubMed ID: 15838253.
    Abstract:
    The aim of this study was to investigate a possible protective role of a selective endothelin-A receptor antagonist on hepatic microcirculation after ischemia/reperfusion. In a rat model, warm ischemia of the left liver lobe was induced for 90 minutes under intraperitoneal anesthesia with xylazine and ketamine. Shamoperated and untreated ischemic groups and a group treated with BSF 208075 were investigated. The effect of the endothelin-A receptor antagonist on ischemia/reperfusion was assessed by in-vivo microscopy and measurement of aspartate aminotransferase and alanine aminotransferase levels. In the untreated group, sinusoidal constriction to 70% of basal diameters was observed, leading to a significant decrease in perfusion rate. In addition, we found an increased percentage of stagnant leukocytes and platelets in sinusoids and in postsinusoidal venules (P < 0.05). A significant increase in liver enzymes was detected 6 hours after reperfusion (P < 0.05). In the treatment group, sinusoidal diameters were maintained at 108%, and perfusion rate was significantly increased (P < 0.05). Hepatocellular damage was decreased and leukocyte and platelet-endothelium interactions were reduced (P < 0.05). Our results provide evidence that the new therapeutic approach using an endothelin-A receptor antagonist is effective in reducing hepatic ischemia/reperfusion injury. It could be shown for the first time that endothelin receptor blockade also influences platelet-endothelium interactions.
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