Naloxone alters organ perfusion during endotoxin shock in conscious rats

Abstract

Antagonism of endogenous opioids has been shown to improve survival time, increase blood pressure, and attenuate acidosis during endotoxin shock. However, some of the most severe problems associated with this condition arise from the circulatory disturbances that occur. We investigated the circulatory effects of naloxone during endotoxin shock as they relate to hemodynamic parameters in conscious, unrestrained rats. Blood flow and hemodynamic variables were measured in male, Sprague-Dawley rats (300-400 g) 24 h after surgical preparation. Rats were challenged with either 10 mg/kg Escherichia coli endotoxin (100% lethal dose) or intravenous saline. Measurements were made at 0, 10, 30, and 60 min postchallenge. Naloxone (2 mg/kg) or saline was given as a treatment (intravenous bolus) at 25 min postchallenge. Cardiac output and blood distribution (%CO) and flow were measured with radiolabeled microspheres. Cardiac output was depressed and total peripheral resistance was elevated 10 min into endotoxin shock. Naloxone treatment improved blood pressure significantly during endotoxin shock, as would be expected with the observed increase in total peripheral vascular resistance and no significant change in cardiac output. Improved perfusion of skeletal muscle is a likely explanation for lower serum lactate levels that have been reported to occur in this model after naloxone administration. Our data also indicate that naloxone may improve cardiac efficiency and does not interfere with maintenance of global cerebral blood flow. Collectively, these effects would contribute to the observed improved survival time after naloxone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)