Illustration of Ranolazine induced Cardioprotection, its possible mechanism of actions & role of adenosine

Objectives: This study was to investigate cardioprotective effects of ranolazine and to explore possible secondary mechanisms beyond the cellular studies have demonstrated inhibition of late sodium channel(I Na L) leads to reduction in calcium load during cardiac ischemia. Methods: An animal model of ischemia-reperfusion injury was established using Langendroff’s technique. 20 minutes ischemia and 40 minutes of reperfusion was given to isolated heart as model of myocardial infarction. There were five groups: Control, Ischemic preconditioning, ranolazine(100µmol/L) treatment in perfusate, ranolazine(100µmol/L)+Theophylline(30µmol/L) and ranolazine(100µmol/L)+ Aminophylline(30µmol/L) in perfusate. Results: Ranolazine found cardioprotection (Infarct Size: 4.79±0.84 compared to control 62.85±8.60; LDH: 73.67±1.33U/L compared to control 102±0.60U/L; CK-MB: 44.83±1.14U/L compared to control 199.33±2.17U/L) Ischeamic Preconditioning found cardioprotection (Infarct Size: 9.11±0.85 compared to control 62.85±8.60; LDH: 73.17±1.33U/L compared to control 102±0.60U/L; CK-MB: 46.50±1.89U/L compared to control 199.33±2.17U/L) Ranolazine+Theophylline (Infarct Size: 21.33±1.22compared to ranolazine 4.79±0.84; LDH: 102.00±6.42U/L compared to ranolazine 73.67±1.33U/L; CK-MB: 110.00±3.20U/L as compared to ranolazine 44.83±1.14U/L) Ranolazine+Aminophylline (Infarct Size: 23.91±0.89as compared to ranolazine 4.79±0.84; LDH: 110.33±4.41as compared to control 73.67±1.33U/L; CK-MB: 117.00±3.47 U/L as compared to ranolazine 44.83±1.14U/L) Conclusions: As per confirmation Ranolazine and ischemic preconditioning have brought cardioprotection as reduced Infract Size, LDH & CK-MB. Wereas, treatment of L-NAME & Aminoguanine in both increased infract size, LDH & CK-MB. Hence it is proved that ranolazine involves adenosine as secondary messenger in cardioprotection.