Abstract 9583: Remote Preconditioning Has a Powerful Antiarrhythmic Effect Independent of the Reperfusion Injury Salvage Kinase Pathways

Abstract

Background: There is continuing need for non pro-arrhythmic antiarrhythmic therapies for life threatening ventricular arrhythmias associated with myocardial ischemia/reperfusion. A new form of endogenous cardio-protection, remote ischemic preconditioning (RPC) showed promise for reducing myocardial infarct size, but its effect on ventricular arrhythmias is largely unknown. The purpose of this study was to determine the effects of RPC on arrhythmias in a non-infarct producing model. Methods: Anesthetized open chest rats were exposed to 5 minutes of proximal left coronary artery occlusion and 10 minutes of reperfusion. Rats were either untreated controls (Ctrl, n=17) or received RPC (n=14) with 5 minutes bilateral femoral occlusions followed by 5 minutes of reperfusion times 3, started 30 minutes before coronary occlusion. Reperfusion arrhythmias were quantitated and in some rats Western Blot Analysis for pAKT and p-p70S6 kinase were studied. Results: Ischemic risk zone (blue dye technique) was similar in Ctrl (35% of LV) and RPC (32%) as were heart rate and blood pressure throughout the study. At reperfusion, onset of ventricular tachycardia (VT) was delayed in RPC group (45.8 ± 17.1 sec; mean + SEM) versus Ctrl (11.5 ± 3.3 sec; p=0.04). The number of episodes of VT was 18.1 ± 5.1 in Ctrl versus 5.2 ± 1.7 in the RPC group (p=0.01) and duration of VT was 67.2 ± 13.2 sec in Ctrl versus 24.9 ± 11.1 sec in RPC (p=0.019). Sustained VT (≥ 10 sec) occurred in 12 controls and 4 RPC rats (p=0.03); and duration of sustained VT was 40.2 ± 9.9 sec in Ctrl versus 14.6 ± 7.2 sec in RPC (p=0.03). Ventricular fibrillation occurred in 3 controls and 1 RPC rat. Mean number of ventricular premature beats was 38.2 ± 11.4 in Ctrl and 14.1 ± 3.1 in RPC rats (p=0.04). At the end of reperfusion p-Akt level in the risk area in control hearts was 2 times higher compared to the non-ischemic area, and was not different from its level in the risk area in the RPC hearts. In addition, the risk area in both Ctrl and RPC hearts demonstrated no difference in the p-p70S6 kinase level. Conclusion: Remote ischemic preconditioning of the lower limbs induced a powerful delay in/and reduction in ischemia/reperfusion induced ventricular arrhythmias, but without evoking the reperfusion injury salvage kinase pathway.