Ischemia-induced canine myocardial lysosome labilization: The role of endogenous prostaglandins and cyclic nucleotides

We tested the hypothesis that alterations in myocardial prostaglandin levels were associated with ischemia-induced lysosome labilization. To test this hypothesis, endogenous prostaglandin synthesis was restricted by administering indomethacin (INDO). After a thoracotomy in dogs, INDO (5 mg/kg) or vehicle was infused iv and 15 min later myocardial ischemia was induced by occlusion of the left anterior descending (LAD) coronary artery and the results compared to sham-operated animals. Myocardial tissue samples were biopsied 3 hr post-LAD ligation, homogenized, and the lysosome fraction subjected to a mild hypo-osmotic shock. The lysosomes from ischemic tissue were more labile compared to lysosomes from nonischemic tissue and this was associated with a decrease in myocardial cAMP cGMP in ischemic tissue. Myocardial cAMP cGMP correlated positively with myocardial lysosome stability ( P < 0.05) and tissue prostaglandin E and A concentrations correlated negatively with myocardial cAMP ( P < 0.05). In an in vitro liver lysosome system, INDO had no effect on enzyme release. These data suggest that ischemia-induced lysosome labilization via an increased prostaglandin release causes a lowered cAMP cGMP .