Effects of pepstatin on reducing hypoxia-induced injury in the isolated guniea pig heart.

Intracellular cathepsin D is thought to play a role in myocardial injury produced by ischemia and hypoxia. Pepstatin, a known inhibitor of cathepsin D, was infused into isolated guniea pig hearts (Langendorff preparation) in order to observe if such an administration of pepstatin would protect against the effects of a two minute exposure to hypoxia. Hypoxia was produced by exposing the hearts to perfusion fluid aerated with 20% 02/5% CO2/75% N2 and containing 0.5 microgram/ml of 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 of pepstatin for 30 minutes produced no significant alterations in the parameters of cardiac function studied. However, this amount of pepstatin inhibited 97% of the cathepsin D activity of the hearts. The characteristics ECG alterations produced by hypoxia were significantly reduced after infusion of pepstatin. These data indicate that pepstatin may protect the heart against hypoxia-induced injury.