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Circulation, Vol 86, 302-310, Copyright © 1992 by American Heart Association

ARTICLES

Metabolic consequences and predictability of ventricular fibrillation in hypoxia. A 31P- and 23Na-nuclear magnetic resonance study of the isolated rat heart

S Neubauer, JB Newell and JS Ingwall
NMR Laboratory for Physiological Chemistry, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.

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.