Ranolazine reduces cellular
acetyl-CoA content via inhibition of
fatty acid beta-oxidation and activates
pyruvate dehydrogenase. This metabolic switch increases
ATP production per mole of
oxygen consumed, reduces the rise in
lactic acid and
acidosis, and maintains myocardial function under conditions of reduced myocardial
oxygen delivery. It is still unclear whether
ranolazine causes a reduction of (i)
infarct size and (ii) cardiac
troponin T release, in a male Wistar rat model of left anterior descending coronary artery occlusion (25 min) and reperfusion (2 h). Rats were subjected to saline infusion (n=12) or
ranolazine (bolus injection: 10 mg/kg plus infusion: 9.6 mg/kg/h, n=12), 30 min prior to left anterior descending coronary artery occlusion-reperfusion, respectively.
Ranolazine caused a significant reduction in
myocardial infarct size of approximately 33% compared to saline control (P<0.05). In addition, infusion of
ranolazine significantly attenuated the release of cardiac
troponin T into the plasma from 65+/-14 (controls) to 12+/-2 ng/ml. This study demonstrates for the first time that
ranolazine significantly reduces (i)
infarct size and (ii) cardiac
troponin T release in rats subjected to left anterior descending coronary artery occlusion-reperfusion.