Role of Lysosomes in the Pathogenesis of Splanchnic Ischemia Shock in Cats

TLDR: The data indicate that the biochemical and hemodynamic alterations present in SAO-induced shock may be related to the disruption of pancreatic lysosomes and that glucocorticoids can markedly alter the course of this shock, possibly by decreasing the sensitivity of pancreas to splanchnic ischemia.

Abstract: Splanchnic arterial occlusion (SAO) for 2 hours followed by release of the occlusion in cats produced a lethal shock state characterized by cardiovascular collapse. Release of the occlusion resulted in a 45% fall in mean arterial blood pressure within 15 minutes; postrelease survival of these animals was 46 minutes. The plasma of cats with SAO shock exhibited a 3- to 4-fold increase in activities of the lysosomal enzymes β-glucuronidase and cathepsin, accompanied by accumulation of a myocardial depressant factor. Plasma from cats treated with methylprednisolone (20 mg/kg) prior to occlusion did not have significant levels of myocardial depressant factor nor significant increases in plasma lysosomal enzyme activity. Furthermore, the fall in mean arterial blood pressure in steroid-treated animals was significantly smaller when the occlusion was released and postrelease survival time was significantly longer. Pancreatic lysosomes from cats with SAO exhibited a marked increase in fragility as indicated by a reduction in total lysosomal enzyme activity and an increase in the percent of free enzyme activity, compared to lysosomes from cats with sham SAO or steroid-treated cats. These data indicate that the biochemical and hemodynamic alterations present in SAO-induced shock may be related to the disruption of pancreatic lysosomes and that glucocorticoids can markedly alter the course of this shock, possibly by decreasing the sensitivity of pancreatic lysosomes to splanchnic ischemia.