Effects of opioid agonists and opioid antagonists in endotoxic shock in rats

Endotoxic shock is presented with a complex pathophysiology and is associated with high mortality. Recently, it has been reported that endogenous opioids play an important role in endotoxic shock. Pressor effect of naloxone in shock may be mediated through antagonism of endogenous opioid inhibition of the sympatho-adrenal catecholaminergic system. In endotoxemic animal, circulating catecholamine levels were not elevated by naloxone. It is possible that naloxone acts upon opiate receptors to enhance catecholamine actions at the receptor level or post-receptor level. We investigated endotoxic shock using a rat model. The animals anesthetized with phenobarbital were infused with E. coli LPS for 30 minutes. They were divided into 5 groups. After an endotoxin i.v. infusion of 15 mg/kg (LD 60), a significant fall in mean arterial pressure (MAP), heart rate and pH occurred in all groups. Treatment with naloxone or buprenorphine or naloxone + epinephrine resulted in significant improvement in MAP, pH and base excess. Treatment with morphine resulted in a decrease in MAP and an increase in heart rate. The pressor response to epinephrine 10, 30, 60 microgram/kg i.v. caused an increase of 62%, 48% and 17% of control values respectively in endotoxic treated rats. The duration of the pressor response to epinephrine was significantly increased by naloxone, although no significant effects on survival were seen at 4 hours after the start of treatment. These findings suggest that the buprenorphine may prove to be an alternative to naloxone, the co-administration of naloxone and epinephrine may be of benefit in the management of septic shock.