Dhalla AK, Wang WQ, Dow J, Shryock JC, Belardinelli L, Bhandari A, Kloner RA
Ranolazine, an Antianginal Agent, Markedly Reduces Ventricular Arrhythmias Induced by Ischemia and Iscehmia-Reperfusion. [JOURNAL ARTICLE]
Am J Physiol Heart Circ Physiol 2009 Sep 18.
We tested the effect of the antianginal agent ranolazine (R) on ventricular arrhythmias in ischemic model using 2 protocols. Methods for Protocol 1: Anesthetized rats received either vehicle or R (10 mg/kg, IV bolus) and were subjected to 5 minutes of left coronary artery (LCA) occlusion and 5 minutes of reperfusion with ECG and blood pressure monitoring. Protocol 2: Rats received either vehicle or three doses of R (IV bolus followed by infusion), and 20 minutes of LCA occlusion. Results of Protocol 1: Ventricular tachycardia (VT) occurred in 9/12 (75%) vehicle - treated rats and 1/11 (9%) R - treated rats during reperfusion (p = 0.003). Sustained VT occurred in 5/12 (42%) vehicle treated but 0/11 R - treated rats (p = 0.037). Median number of episodes of VT during reperfusion in vehicle and R rats was 5.5 and 0, respectively (p = 0.0006); median duration of VT was 22.2 and 0 seconds in vehicle and R rats, respectively (p = 0.0006). Protocol 2: Mortality in the vehicle group was 42% versus 17% (p=0.371) , 10% (p=0.162) and 0% (p=0.0373) with R at plasma concentrations of 2, 4 and 8 microM, respectively. R significantly reduced the incidence of ventricular fibrillation (VF) (67% in controls vs. 42 % (p=0.414), 30% (p=0.198) and 8% (p=0.0094) in R at 2, 4 and 8 microM, respectively). Median number (2.5 vs. 0; p = 0.0431) of sustained VT episodes, incidence of sustained VT (83% vs. 33%, p=0.0361) and the duration of VT per animal (159 vs. 19 seconds; p = 0.0410) were also significantly reduced by R at 8 microM. R markedly reduced -ischemia/reperfusion induced ventricular arrhythmias. R demonstrated promising anti-arrhythmic properties which warrants further investigation. Key words: arrhythmias, ranolazine, myocardial ischemia/reperfusion, ventricular tachycardia.
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