Abstract 7: Enhancing Glucose Oxidation Following Ventricular Fibrillation Resuscitation Mitigates Cardiac Systolic Dysfunction

Abstract

Background: Ventricular fibrillation (VF) is an important cause of cardiac arrest. After initial successful resuscitation, decreased cardiac contractility during reperfusion is a common problem that is poorly understood. In normal hearts the major energy source for cardiac contractility is oxidation of fatty acids (FA), while only a lesser amount of energy originates from glucose oxidation. Previous investigations showed that during and after ischemia, cardiac contractile dysfunction depends on the type of energy substrate metabolized, with increased FA oxidation and decreased glucose oxidation not being beneficial. Increasing glucose oxidation and decreasing FA oxidation has not been evaluated as a strategy to improve contractile dysfunction following VF resuscitation. One such approach could be the use of dichloroacetate (DCA), a metabolic modulator that increases glucose oxidation and decreases FA oxidation. Methods and Results: Rat hearts (n=40) were Langendorff-perfused in Tyrode’s buffer and allowed to equilibrate for 15min followed by 15min of global ischemia and 5min of reperfusion. During reperfusion a short duration burst pacing stimulation was used to induce VF. Hearts were divided into two groups; untreated control (n=20) and DCA-treated during reperfusion (1mM; n=20). One minute later VF was terminated. Left ventricular (LV) pressure, heart rate and coronary flow were monitored during the post VF period. The incidence of VF was 60% in untreated controls, and 66% in DCA-treated hearts. LV developed pressure (LVDP) was reduced after VF and post-resuscitation period compared to the baseline period (90.7±3.5mmHg vs 52.3±6.8mmHg, respectively, n=8, p<0.01). DCA improved post-resuscitation LVDP (74.3±6.5mmHg, n=8, p<0.05 vs untreated controls). Post-resuscitation lactate production was reduced in DCA-treated hearts compared to untreated controls (1.0±0.3µM/g/min vs 1.9±0.2µM/g/min, n= 8, p<0.05). Conclusions: Cardiac contractility is impaired following resuscitation after VF. Enhancement of glucose oxidation with DCA mitigates post VF cardiac dysfunction and may have a therapeutic role under these conditions.