Abstract 13307: Inorganic Pyrophosphate (PPi) Protects Against Early Asystole in Ex-Vivo Model of Cardiac Arrest and Prevents Mitochondrial Depolarization in Hypoxic Cardiomyocytes
Asystole following ventricular fibrillation (VF) and global ischemia (VF/ischemia) is a typical and adverse outcome of cardiac arrest. We hypothesized that the incidence of asystole may depend on pre-ischemic differences in energy metabolism. Tissue samples were obtained from the left ventricle of 10 canine hearts prior to 20 min of VF/ischemia. Asystole was defined as complete electrical standstill or sporadic rhythm < 20 beats/min. Asystole occurred in two distinct time intervals: between 5.2 and 8.2 min of ischemia (early-asystole group, n=6) and after 16.2 min of ischemia (late-asystole group, n=4). Among 67 metabolites relevant to energy metabolism, the largest difference was found in the pre-ischemic level of PPi, which was 24.9 times higher in late-asystole than in early-asystole hearts (p=0.019). It was previously shown in non-cardiac models that PPi may contribute to the maintenance of mitochondrial membrane potential ([[Unable to Display Character: ∆]]Ψm) under conditions of metabolic inhibition. We hypothesized that PPi might prevent loss of [[Unable to Display Character: ∆]]Ψm during hypoxic stress in cardiac myocytes. To test this hypothesis, we measured [[Unable to Display Character: ∆]]Ψm during 10 min of near-anoxia (pO2 ≈ 0) using potentiometric probe TMRM in rat neonatal cardiomyocytes incubated overnight with 0.1 mM of PPi versus control group. Myocytes in control group experienced significant loss of [[Unable to Display Character: ∆]]Ψm-dependent fluorescence during 10 min of anoxia (76.0 ± 5.4% of baseline at 5 min and 57.6 ± 6.0% of baseline at 10 min of anoxia, Figure 1A-C and G). In contrast, in the PPi-treated myocytes [[Unable to Display Character: ∆]]Ψm was either unchanged or slightly hyperpolarized during anoxia (109.5 ± 19.4 % of baseline at 5 min and 106.6 ± 8.6% of baseline at 10 min of anoxia, Figure 1D-F and G). Our results show that PPi may be cardioprotective by preventing [[Unable to Display Character: ∆]]Ψm depolarization at the early phase of hypoxic stress. This effect offers a plausible explanation for the association between the high pre-ischemic tissue level of PPi and the postponement of asystole in the canine model of VF/ischemia.
- Mitochondrial energetics, heart failure, arrhythmias
- Cardiac arrest
- Ventricular fibrillation
- © 2012 by American Heart Association, Inc.