A CORRELATION OF THE EFFECTS OF CERVICAL CORDOTOMY, HYPOTHERMIA, AND CATECHOLAMINES ON CARBON TETRACHLORIDE-INDUCED HEPATIC NECROSIS

¹ Department of Pharmacology, College of Medicine, State University of Iowa, Iowa City, Iowa

Spinal cord transection of rats at C-7 resulted in generally higher blood and liver concentrations of CCl₄ over a 24-hour period than were observed in intact rats after a single oral dose of the agent. However, 24 hours after a single dose of CCl₄ cordotomized rats did not exhibit the typical hepatic degenerative changes that were seen in intact rats. Instead, the lesion developed over a longer time course, becoming fully developed between 55 and 65 hours after treatment. Cordotomized rats rapidly became hypothermic following the surgery. Hypothermia induced by immersion of intact rats in water resulted in a protective effect comparable to cordotomy against CCl₄. This method of inducing hypothermia also resulted in liver concentrations of CCl₄ that followed a pattern similar to that seen after cordotomy.

Whole-body O₂ consumption was reduced to about 50% of normal by 1 hour and to about 30% by 5 hours after cord transection. Depression of body temperature sufficient to account for these decreases was observed in this time. Water immersion also resulted in a markedly reduced rate of O₂ consumption.

The infusion of high concentrations of norepinephrine, epinephrine or mixtures of the two for 20 hours did not induce a CCl₄-like hepatic lesion nor a potentiation of CCl₄ effects in cordotomized rats.

These results support the hypothesis that the protective effect of cervical cordotomy against CCl₄-hepatotoxicity lies in the reduced hepatic metabolism produced by the hypothermia produced by the surgery.