Dihydralazine treatment limits liver injury after hemorrhagic shock in rats

OBJECTIVE:Impaired hepatic perfusion after hemorrhagic shock frequently results in hepatocellular dysfunction associated with increased mortality. This study characterizes the effect of the vasodilators dihydralazine and urapidil on hepatocellular perfusion and integrity after hemorrhagic shock and resuscitation. DESIGN:Prospective, randomized, controlled experimental study. SETTING:University experimental laboratory. SUBJECTS:Male Sprague-Dawley rats. INTERVENTIONS:To register systemic and regional hepatic hemodynamics, rats (n = 6 per group) were instrumented and randomly assigned to the following groupsshock + vehicle; shock + dihydralazine (1.5 mg/kg); or shock + urapidil (3 mg/kg). After 1 hr of hemorrhagic shock, animals were resuscitated for 5 hrs and mean arterial pressure was maintained at 70 ± 5 mm Hg by administration of dihydralazine or urapidil. To evaluate hepatic heme oxygenase-1 expression and liver injury (determination of levels of alanine and aspartate aminotransferase [ALT, AST] and histology), an additional series of experiments with six animals per group was performed. At the end of each experiment, animals were killed and blood and liver tissue was obtained for subsequent analyses. MEASUREMENTS AND MAIN RESULTS:Dihydralazine increased cardiac output and portal and hepatic microvascular flow (p < .05) and reduced liver injury after shock (lower ALT and AST levels [p < .05]; improvement of histopathological changes). In contrast, urapidil had no effect on portal flow or liver injury. Hepatic heme oxygenase-1 mRNA expression was upregulated in animals subjected to hemorrhagic shock but did not differ among experimental groups. CONCLUSIONS:Dihydralazine increases nutritive portal and hepatic microvascular flow and limits liver injury after hemorrhagic shock. This protective effect appears to be the result of increased cardiac output and increased portal flow. These findings may offer a new strategy for hepatic protection after hemorrhagic shock.