Ranolazine is an inhibitor of the late
sodium current and, via this mechanism, decreases
sodium-dependent intracellular
calcium overload during
ischemia and reperfusion.
Ranolazine reduces angina, but there is little information on its effects in acute
myocardial infarction. The aim of this study was to test the effects of
ranolazine on left ventricular (LV) function and
myocardial infarct size after
ischemia/reperfusion in rabbits. Ten minutes before coronary artery occlusion (CAO), anesthetized rabbits were assigned to vehicle (n=15) or
ranolazine (2 mg/kg i.v. bolus plus 60 microg/kg/min i.v. infusion; n=15). Hearts received 60 min of CAO and 3 h of reperfusion. CAO caused
LV dysfunction associated with
necrosis. However, at the end of reperfusion, rabbits treated with
ranolazine had better global LV ejection fraction (0.42+/-0.02 versus 0.33+/-0.02; p<0.007) and stroke volume (1.05+/-0.08 versus 0.78+/-0.07 ml; p<0.01) compared with vehicle. The fraction of the LV wall that was akinetic or dyskinetic was significantly less in the
ranolazine group at 0.23+/-0.03 versus 0.34+/-0.03 in vehicle-treated group; p<0.02. The ischemic risk region was similar in both groups; however,
infarct size was significantly smaller in the treated group (44+/-5 versus 57+/-4% vehicle; p<0.04). There were no significant differences among groups in heart rate, arterial pressure, LV end-diastolic pressure, or maximum-positive or -negative first time derivative of LV pressure (dP/dt). In conclusion, the results of this study show that
ranolazine provides protection during acute
myocardial infarction in this rabbit model of
ischemia/reperfusion.
Ranolazine treatment led to better ejection fraction, stroke volume and less wall motion abnormality after reperfusion, and less myocardial
necrosis.