| Summary: | BACKGROUND: Ventricular fibrillation has deleterious metabolic and functional consequences for the heart. This study had two purposes: first, to define the effects of ventricular fibrillation during hypoxia on energy metabolism and accumulation of intracellular Na+ and, second, to test whether the occurrence of ventricular fibrillation can be predicted from functional or metabolic parameters. METHODS AND RESULTS: Isolated isovolumic rat hearts were perfused with oxygenated Krebs-Henseleit buffer at 37 degrees C. After a prehypoxic period, hearts were subjected to hypoxic perfusion (95% N2-5% CO2) for 30 minutes. High-energy phosphates and intracellular pH were determined by 31P-nuclear magnetic resonance (NMR) spectroscopy, and intracellular Na+ accumulation was followed by 23Na-NMR spectroscopy in combination with the shift reagent dysprosium triethylenetetraminehexa-acetate. Five of 10 (31P-NMR) and four of 10 (23Na-NMR) hearts developed spontaneous ventricular fibrillation at 19 +/- 2 minutes (31P-NMR) and 18 +/- 3 minutes (23Na-NMR) of hypoxia (ventricular fibrillation group), whereas other hearts (non-ventricular fibrillation group) remained beating throughout hypoxia. Cardiac function and high-energy phosphate content declined during hypoxia, and ventricular fibrillation exacerbated this decline significantly. Similarly, ventricular fibrillation exacerbated the accumulation of intracellular Na+ occurring during hypoxia. Statistical analysis showed that the event of ventricular fibrillation could be predicted from changes of end-diastolic pressure, rate-pressure product, and creatine phosphate content before ventricular fibrillation. However, the strongest predictor of ventricular fibrillation was intracellular Na+ accumulation, which occurred in ventricular fibrillation hearts throughout the hypoxic period long before ventricular fibrillation was initiated. CONCLUSIONS: Loss of systolic and diastolic functions, creatine phosphate depletion, and, in particular, intracellular Na+ accumulation may be causally related to induction of ventricular fibrillation during hypoxia, all of which are most likely linked to concomitant intracellular Ca2+ accumulation.
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