EFFECTS OF PEPSTATIN ON REDUCING HYPOXIA-INDUCED INJURY IN THE ISOLATED GUINEA-PIG HEART

  • 1 January 1982
    • journal article
    • research article
    • Vol. 37  (2) , 243-258
Abstract
Intracellular cathepsin D may play a role in myocardial injury produced by ischemia and hypoxia. Pepstatin, a known inhibitor of cathepsin D, was infused into isolated guinea pig hearts (Langendorff preparation) to observe if such an administration of pepstatin would protect against the effects of a 2-min exposure to hypoxia. Hypoxia was produced by exposing the heart to perfusion fluid aerated with 20% O2/5% CO2/75% N2 and containing 0.5 .mu.g/ml norepinephrine. Contractile force, heart rate, coronary flow and ECG were monitored. Samples of heart tissue were assayed for cathepsin D activity. Infusion of 0.06 mg/min pepstatin for 30 min produced no significant alterations in the parameters of cardiac function studied. This amount of pepstatin inhibited 97% of the cathepsin D activity of the hearts. The characteristic ECG alterations produced by hypoxia were significantly reduced after infusion of pepstatin. Pepstatin may protect the heart against hypoxia-induced injury.