Infarct size reduction with coronary venous retroinfusion of diltiazem in the acute occlusion/reperfusion porcine heart model

Abstract

Calcium channel blockers are commonly used for the treatment of ischemic heart disease, but their effects on myocardial infarct size (IS) after reperfusion are not well known. Enflurane-anesthetized open-chest pigs subjected to 60-min left anterior descending coronary artery (LAD) occlusion followed by 3-h reperfusion were referred to one of the four experimental groups. Beginning 10 min before the onset of reperfusion, pigs in group A received diltiazem (7.5 micrograms/kg/min) retrogradely infused into the coronary vein for 30 min. In group B, the same amount of diltiazem was infused into the right atrium. A corresponding volume of saline was infused into the coronary vein in group C or into the right atrium in group D. IS expressed as a percentage of the myocardium at risk was significantly smaller (p < 0.01) in group A (33 +/- 14%; mean +/- SD) than in groups B (58 +/- 11%), C (58 +/- 11%), and D(63 +/- 10%). After reperfusion, functional recovery of the ischemic myocardium, determined by ultrasound crystals, was significantly more improved (p < 0.05) in group A as compared with other groups. The ischemic and nonischemic regional myocardial blood flow (RMBF), determined by radioactive microspheres, did not differ between four groups. Coronary venous retroinfusion of diltiazem had a myocardial protective effect in the porcine experimental model of acute coronary occlusion/reperfusion, whereas intravenous drug administration was not effective. The protective effect could not be attributed to washout of toxic metabolites from the ischemic area or to improved microcirculation. It was probably related to a pronounced accumulation of the calcium-channel blocker diltiazem in the ischemic myocardium achieved by the coronary venous route of delivery.