Influence of increased circulating levels of splanchnic lysosomal enzymes on the response to myocardial ischemia.
The ability of increased circulating activities of lysosomal hydrolases to disrupt myocardial cellular membranes was studied in anesthetized cats. Increased activities of lysosomal hydrolases were achieved by splanchnic artery occlusion (SAO) shock or by infusion of liver extract (LE). Myocardial ischemia (MI) was produced by ligation of the left coronary artery. Coronary artery ligation resulted in sustained S-T segment elevation associated with significant increases in plasma creatine phosphokinase (CPK) activity within 5 hours. Combinations of SAO or LE infusion did not modify the increase in either the plasma CPK activity or the S-T segment following MI. However, SAO shock or infusion of LE increased CPK loss from normal and ischemic myocardium, the loss being greater when MI was combined with infusion of LE or SAO shock. Similarly, MI plus SAO shock increased the loss of the lysosomal protease cathepsin D from normal and ischemic myocardial tissue. Moreover, cats subjected to MI and given LE inhibited increased mortality and decreased clearance of infused lysosomal hydrolases. These results indicate that conditions affecting increased plasma levels of hydrolases promote increased disruption of normal and ischemic myocardial tissue. These findings are consistent with the concept that hydrolases originating in the splanchnic viscera during shock play a role in enhancing damage to normal and ischemic myocardial tissue following coronary artery occlusion.
D000005:Abdomen / Q000098:blood supply; D000818:Animals; D002403:Cathepsins / Q000097:blood; D002415:Cats; D003327:Coronary Disease / Q000201:enzymology*; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008110:Liver Extracts / Q000009:adverse effects; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology; D012039:Regional Blood Flow
D008110:Liver Extracts; D003402:Creatine Kinase; D002403:Cathepsins