Protection of coronary reperfusion injury by a calcium antagonist.

The anterior descending branch of the left coronary artery (LAD) of the dog was ligated for 2 hours and thereafter reperfusion was continued for 1 hour. The regional myocardial blood flow (RMBF) during reperfusion was measured by a radioactive microsphere method. Whether a decrease in RMBF in the reperfused region could be prevented by injection of a calcium antagonist "diltiazem hydrochloride (diltiazem)" to LAD during reperfusion was simultaneously studied. RMBFs in ischemic epicardial (Epi) and endocardial (End) layers and End/Epi ratio 5 minutes after reperfusion were 1.87 ml/min/g, l.75 ml/min/g and 1.06 respectively, showing an increase in all values compared to the values in normal region. RMBFs in the Epi and End and End/Epi ratio 60 minutes after reperfusion were 0.99 ml/min/g, 0.91 ml/min/g and 1.05 respectively, showing a decrease in all values without occurrence of transmural flow gradient. The decrease in RMBFs in the Epi and End 60 minutes after reperfusion could be prevented by diltiazem to show 1.68 ml/min/g and 1.42 ml/min/g respectively which were within normal limits. RMBFs in normal Epi which could be perfused by diltiazem were 1.31 and 1.70 ml/min/g before and after injection of diltiazem while those in normal End before and after injection of the drug were 1.27 and 1.46 ml/min/g respectively; RMBFs in both layers could be increased by diltiazem, with the significant increase in RMBF of normal Epi to show a decrease in the End/Epi ratio after injection of the drug. The conclusions are as follows: (1) Diltiazem increases RMBF in normal myocardium. (2) The gradual decrease in RMBF after reperfusion can be inhibited by the drug so that myocardial injury may be reduced. (3) A possibility exists that clinically the drug is a promising agent for early revascularization.