Sustained Myocardial Protection by Clentiazem (TA-3090) After a 90-Minute Coronary Occlusion and 72 Hours of Reperfusion in Dogs with Collateral Flow

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Abstract
Reduction of infarct size by calcium channel blockers, given at reperfusion, has been reported with diltiazem and clentiazem after 6 h of reperfusion following a 90-min coronary occlusion in the dog. The aims of the present study were to establish that the postischemic cardioprotection is not simply a delay in cell death, but a sustained or permanent myocardial salvage. Dogs with a 90-min occlusion of the left descending coronary artery underwent reperfusion for 72 h. Five minutes before reperfusion, they received, at random, i.v. saline (controls) or clentiazem (125 micrograms/kg i.v.), followed by infusion of 1 microgram/kg/min, until sacrifice. Transmural collateral flow measured 15 min after occlusion with radioactive microspheres was not statistically different between groups [(means +/- SE) control: 0.123 +/- 0.040; treated: 0.150 +/- 0.042 ml/min/g]. The area at risk (percentage of left ventricle), delimited by Evans blue perfusion was also similar (control: 39.9 +/- 1.5%; treated: 42.4 +/- 1.6%). Infarct size, estimated as percentage of the area at risk by triphenyltetrazolium chloride and histology, was reduced (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 with 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.

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