EFFECT OF TRIMETAZIDINE ON POSTISCHEMIC REGIONAL MYOCARDIAL STUNNING IN THE HALOTHANE-ANESTHETIZED DOG

Trimetazidine (TMZ) has been described as a new antiischemic agent. Wh ereas its precise mechanism of action remains unknown, antioxidant pro perties and the ability to pre serve high-energy phosphate metabolism have been reported. Accordingly, we studied whether TMZ may limit post ischemic regional myocardial stunning (known to be caused by reactive oxygen species) and influence recruitment of contractile reserve by in otropic stimulation in a dog model, using halothane to maintain steady anesthesia throughout the experiment. Dogs were submitted to a 15-min coronary artery occlusion followed by reperfusion. The blinded protoc ol included a 3-day oral pretreatment (1 mg/kg/day), a bolus injection (0.5 mg/kg), followed by intravenous infusion (0.5 mg/h) initiated 15 min before coronary artery occlusion. Despite lower heart rate (HR) a nd significant reduction of lipid peroxidation in treated dogs, myocar dial stunning and recruitment of contractile reserve by dobutamine inf usion in the postischemic myocardium were not modified by TMZ. Adenine nucleotide pool in the postischemic myocardium was considerably reduc ed as compared with the nonischemic myocardium in both groups. Therefo re, in halothane-anesthetized dogs, the antioxidant properties of TMZ were not sufficient to protect myocardium in terms of postischemic dys function after 15-min ischemia.