SUSTAINED MYOCARDIAL PROTECTION BY CLENTIAZEM (TA-3090) AFTER A 90-MINUTE CORONARY-OCCLUSION AND 72 HOURS OF REPERFUSION IN DOGS WITH COLLATERAL FLOW

Reduction of infarct size by calcium channel blockers, given at reperf usion, has been reported with diltiazem and clentiazem after 6 h of re perfusion following a 90-min coronary occlusion in the dog. The aims o f the present study were to establish that the postischemic cardioprot ection is not simply a delay in cell death, but a sustained or permane nt myocardial salvage. Dogs with a 90-min occlusion of the left descen ding coronary artery underwent reperfusion for 72 h. Five minutes befo re reperfusion, they received, at random, i.v. saline (controls) or cl entiazem (125 mug/kg i.v.), followed by infusion of 1 mug/kg/min, unti l sacrifice. Transmural collateral flow measured 15 min after occlusio n with radioactive microspheres was not statistically different betwee n groups (means +/- SE) control: 0.123 +/- 0.040; treated: 0.150 +/- 0.042 ml/min/g!. The area at risk (percentage of left ventricle), deli mited by Evans blue perfusion was also similar (control: 39.9 +/- 1.5% ; treated: 42.4 +/- 1.6%). Infarct size. estimated as percentage of th e area at risk by triphenyltetrazolium chloride and histology, was red uced (p < 0.05) in treated dogs (control, 42.4 +/- 4.7%; treated, 26.5 +/- 5.4%) with collateral flow (>0.02 ml/min/g), but not in those wit h virtually no (<0.02 ml/min/g) collateral flow (control, 62.0 +/- 8.9 %; treated, 72.7 +/- 6.8%). Therefore clentiazem, at reperfusion after a 90-min ischemia, increases myocardial salvage limiting postischemic injury and providing sustained reduction of infarct size in dogs with collateral blood flow.