Vascular changes associated with development of irreversible endotoxin shock

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Abstract
Recent reports from this laboratory have described the hemodynamic effects of endotoxin in the dog, cat, rabbit, and monkey. To determine the role of peripheral vascular changes in the onset of irreversible shock, isolated denervated dog legs were perfused by means of a pump-lung or dog-pump apparatus. Following endotoxin, dogs liberated vasoactive substances which had profound effects on the perfused organ. Large changes in leg arterial resistance and increases in small vein pressure were seen, which resulted in the formation of edema. Vascular responses of legs to pressor agents in late shock appear abnormal in that venous resistance increases while arterial responses diminish. This, in conjunction with the increased level and activity of histamine, may account for the development of the irreversible period. These findings explain the reported harmful effects of pressor agents when used therapeutically and provide a rationale for the protective actions of adrenergic and histamine-blocking drugs. The study serves to underscore the significance of recently reported findings on the primate in endotoxin shock.