Pathogenesis of Experimental Shock

Fatal shock was produced in animals by drum trauma, temporary occlusion of the superior mesenteric artery, and bacterial endotoxin. Measurements were made of release of beta glucuronidase and cathepsins from the large granule fractions of livers, and of levels of circulating beta glucuronidase and acid phosphatase in these animals. Experiments were also carried out with animals rendered tolerant by previous exposure to sublethal amounts of trauma or by pretreatment with cortisone. The results show that release of beta glucuronidase and cathepsins from the large granule fraction of liver was increased during traumatic and endotoxin shock in the rat. Similarly, circulating levels of acid phosphatase and beta glucuronidase were increased during traumatic shock in rats and rabbits, and during endotoxin shock in rats. The data also indicate that tolerance to traumatic injury, induced by prior conditioning, prevented the increase in levels of circulating acid phosphatase normally observed after stress, and may have been associated with an increased stability of hepatic lysosomal particles. In addition, cortisone, which appears to "stabilize" hepatic lysosomes in vivo, also reduced the increase in plasma acid phosphatase brought about by endotoxin and trauma. From the foregoing observations, it is suggested that: (a) Disruption of lysosomes and release of their contained enzymes in free, active form may occur in liver and intestine of shocked animals. (b) The activation of lysosomal hydrolases within cells and their release into the circulation may play an important role in exacerbating tissue injury and accelerating the development of irreversibility during shock. (c) The increased stability of lysosomes of tolerant and of cortisone-treated animals may constitute an important component of the resistance of these animals to shock.