Ranolazine, a partial fatty acid oxidation inhibitor, reduces myocardial infarct size and cardiac troponin T release in the rat.
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.
Zacharowski
K
K
Department of Cardiac, Vascular and Inflammation Research, The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, EC1M 6BQ, London, UK. k.zacharowski@mds.qmw.ac.uk
Blackburn
B
B
Thiemermann
C
C
D000083:Acetanilides; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D015425:Myocardial Reperfusion; D010084:Oxidation-Reduction / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D000069458:Ranolazine; D051381:Rats; D017208:Rats, Wistar; D020107:Troponin T / Q000097:blood* / Q000378:metabolism
D000083:Acetanilides; D005227:Fatty Acids; D010879:Piperazines; D020107:Troponin T; D000069458:Ranolazine