Mechanisms involved in the effect of M6434 on experimental hemorrhagic shock: II. Effects on energy metabolism and organ blood flow.

Effects of M6434 on survival time and hepatic energy metabolism of hemorrhagic-shocked rats were examined. Effects of the compound on rat mitochondrial respiration and regional blood flow in hemorrhagic-shocked rats were also studied to clarify the mechanisms of the antishock effects. Intravenous infusion of M6434 (3 or 10 micrograms/kg/min) prolonged the survival time of hemorrhagic-shocked rats. M6434 at 10 micrograms/kg/min significantly suppressed the decline of adenosine triphosphate contents and energy charge of the liver, shifted the blood flow distribution from skin and skeletal muscles to vital organs such as the liver and the heart, and also increased cardiac output in hemorrhagic-shocked rats. The mitochondrial respiration was unaffected by M6434 in vitro (10(-6)-10(-5) M). These data suggest that mechanisms of the beneficial effect of M6434 in hemorrhagic-shocked rats may not be based on the direct activation of energy metabolism, but rather on the redistribution of organ blood flow as well as an increase in cardiac output.