Experimental Endotoxin Shock: The Pathophysiologic Function of Endorphins and Treatment with Opiate Antagonists

Abstract

The specific opiate-antagonist naloxone rapidly reverses hypotension caused by endotoxin, hypovolemia, and spinal transection. In endotoxin shock in rats, naloxone's effects were stereospecific and were observed with intravenous (iv) doses as low as 0.1 mg/kg. In endotoxin shock in dogs, naloxone treatment significantly improved both cardiovascular parameters and survival. Naloxone, given iv, similarly improved blood pressure and survival in rat and canine models of hypovolemic shock. Moreover, intracerebroventricular (ivt) naloxone at a dose of 10 lAg restored blood pressure after hypovolemia; this effect was blocked by hypophysectomy. In addition naloxone, given ivt, stereospecifically restored blood pressure after spinal shock. From these findings it is suggested that (1) pituitary endorphins are pathophysiologic factors in shock; (2) endorphins' cardiodepressant effects are mediated by opiate receptors within the central nervous system; and (3) use of opiate antagonists may be of therapeutic benefit in the treatment of shock in humans.