The protective effects of nifedipine in the isolated cat heart

The calcium channel blocking agent, nifedipine, was studied during global ischemia and reperfusion in isolated cat hearts perfused with Krebs-Henseleit solution. Nifedipine was added to the reservoir and 0.1 micrograms/ml perfusate/hr of nifedipine was infused for 150 min. After 120 min of ischemia (flow at 1% of control), the heart was reperfused with nifedipine-containing perfusate for 20 min and with nifedipine-free perfusate for an additional 25 min. In control hearts, nifedipine significantly reduced the percent free activity of the lysosomal protease cathepsin D (P less than 0.01). In ischemic hearts, nifedipine protected against the increased myocardial tissue edema (P less than 0.01), the increased percent free cathepsin D activity (P less than 0.02) and the postreperfusion increased creatine kinase activity (P less than 0.01). Thus, nifedipine showed membrane stabilizing and cytoprotective activities in myocardial cells, after postischemic reperfusion. These data suggest that calcium ions contribute to the lysosome labilization and cytoplasmic enzyme leakage observed in ischemia and reperfusion, and that calcium channel blockade may protect myocardial cellular integrity during both ischemia and reperfusion.