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)