²³Na and ³¹P nuclear magnetic resonance studies of ischemia-induced ventricular fibrillation: Alterations of intracellular Na⁺ and cellular energy

To clarify the role of Na⁺_i, pH_i, and high-energy phosphate (HEP) levels in the initiation and maintenance of ischemia-induced ventricular fibrillation (VF), interleaved ²³Na and ³¹P nuclear magnetic resonance spectra were collected on perfused rat hearts during low-flow ischemia (51 minutes, 1.2 mL/g wet wt). When untreated, 50% of the hearts from normal (sham) rats and 89% of the hypertrophied hearts from aorticbanded (band) rats (P<.01 versus sham) exhibited VF. Phosphocreatine content was significantly higher in sham than band hearts during control perfusion (53.3±1.6 versus 39.8±2.0 μmol/g dry wt). Before VF at 20 minutes of ischemia, Na⁺_i accumulation was greater in hearts that eventually developed VF than in hearts that did not develop VF for both band and sham groups (144% versus 128% of control in sham; P<.005) and was the strongest metabolic predictor of VF; ATP depletion was also greater for VF hearts in the sham group. Infusion of the Na⁺-H⁺ exchange inhibitor 5-(N,N-hexamethylene)-amiloride prevented VF in sham and band hearts; reduced Na⁺_i accumulation but similar HEP depletion were observed compared with VF hearts before the onset of VF. Rapid changes in Na⁺_i, pH_i, and HEP began with VF, resulting in intracellular Na⁺_i overload (≈300% of control) and increased HEP depletion. A delayed postischemic functional recovery occurred in VF hearts, which correlated temporally with the recovery of Na⁺_i. In conclusion, alterations in Na⁺_i were associated with spontaneous VF transitions, consistent with involvement of excess Na⁺_i accumulation in VF initiation and maintenance and with previously reported alterations in Ca²⁺_i with VF. Hypertrophied band hearts exhibited enhanced susceptibility to ischemia-induced VF, possibly linked to a lower HEP reserve.