NALOXONE REVERSAL OF HYPOVOLEMIC SHOCK IN DOGS

Abstract

The endogenous opiate ligand .beta.-endorphin is released during stress. The hypothesis that endorphins may be involved in the pathophysiology of hemorrhagic shock was tested using the opiate receptor blocking agent, naloxone. Two groups of 5 anesthetized dogs were instrumented to monitor cardiovascular performance and subjected to a protocol in which they were bled into a reservoir to lower mean arterial pressure to 45 mm Hg and maintained at that pressure for 1 h. At that time the reservoir was clamped and 1 group of dogs received an i.v. bolus of naloxone (2 mg/kg) and an infusion at 2 mg/kg per h. These dogs demonstrated a prompt increase in arterial pressure, left ventricular dp/dtmax [1st derivative of the pressure] and cardiac output. The shed blood was returned at t = 2 h and drug infusion continued for 2 h. The control group of dogs received saline in equivalent volume. The control dogs died within 30 min of clamping the reservoir while all 5 treated dogs survived beyond 72 h (P < 0.02). Endorphins apparently act on opiate receptors as part of the pathophysiology in this shock model.