23 Na and 31 P Nuclear Magnetic Resonance Studies of Ischemia-Induced Ventricular Fibrillation

Abstract

Abstract 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 23 Na and 31 P 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 aortic-banded (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 Ca 2+ i with VF. Hypertrophied band hearts exhibited enhanced susceptibility to ischemia-induced VF, possibly linked to a lower HEP reserve.