Study of chemical sympathectomy in endotoxin-induced lethality and fibrin depostion.

Shock and the generalized Shwartzman reaction are well known features of endotoxin which have been shown to involve the sympathetic nervous system. The mechanism of sympathetic nervous system involvement with endotoxin injection was studied in rabbits chemically sympathectomized with 6-hydroxydopamine. Endotoxin, in doses producing a spectrum of morbidity and mortality in normal rabbits, was administered i.v. to chemically sympathectomized, normal, and unilateral renal surgically sympathectomized animals. Chemical sympathectomy produced a significant depletion of tissue norepinephrine which, in endotoxin recipient animals, was associated with a significantly lower mortality rate and greatly decreased fibrin deposition in the lungs and kidneys, despite intravascular coagulation. Unilateral renal sympathectomy afforded protection to the ipsilateral kidney, but data on mortality and systemic fibrin deposition were similar to those reported for normal rabbits given endotoxin. Six-hydroxydopamine prevents significant tissue injury secondary to endotoxin in this experimental model. In addition, the data provide direct evidence that an intact reactive sympathetic nervous system is essential for development of lethal toxicity and generalized Shwartzman reaction due to endotoxin.