EFFECT OF RANOLAZINE ON INFARCT SIZE IN A CANINE MODEL OF REGIONAL MYOCARDIAL ISCHEMIA REPERFUSION/

We assessed ranolazine's potential to reduce myocardial injury resulti ng from 90-min occlusion and 18-h reperfusion of left circumflex coron ary artery (LCX) in anesthetized dogs. Ranolazine, a putative antiangi nal agent, has exhibited positive results in a variety of experimental models associated with the ischemic myocardium. Previous studies demo nstrated that ranolazine possesses a mechanism of action involving inc reases in the amount of active pyruvate dehydrogenase during ischemia, suggesting that the compound may act to promote glucose utilization. Ranolazine was administered as a bolus of 3.3 mg/kg, followed by a con stant infusion of 7.2 mg/kg/h for 20 h. The loading dose was administe red 30 min before LCX occlusion. Control animals received appropriate volumes of vehicles (loading and infusion). Hemodynamics were unchange d between ranolazine and vehicle groups. Three animals in each group w ere excluded because of ventricular fibrillation (VF). There was no di fference in degree of ST segment change between control and ranolazine -treated groups at any time during LCX occlusion. The area at risk (AA R) of infarct was 40.1 +/- 1.7 and 38.9 +/- 1.3% in control-treated (n = 13) and ranolazine-treated (n = 8) animals, respectively (p = 0.631 ). Myocardial infarct size (IS) was 31.7 +/- 5.2 and 36.6 +/- 8.5% in control and ranolazine-treated animals, respectively (p = 0.603). No s ignificant changes were observed in plasma content of enzymatic marker s at 0.5, 2.0, and 18.0 h of reperfusion. The results of this in vivo study indicate that ranolazine did not provide protection from injury to regionally ischemic and reperfused myocardium despite its reported antiischemic activity.