NA-23 AND P-31 NUCLEAR-MAGNETIC-RESONANCE STUDIES OF ISCHEMIA-INDUCEDVENTRICULAR-FIBRILLATION - ALTERATIONS OF INTRACELLULAR NA-ENERGY( AND CELLULAR)

To clarify the role of Na-i(+), pH(i), and high-energy phosphate (HEP) levels in the initiation and maintenance of ischemia-induced ventricu lar fibrillation (VF), interleaved Na-23 and P-31 nuclear magnetic res onance spectra were collected on perfused rat hearts during low-flow i schemia (51 minutes, 1.2 mL/g wet wt). When untreated, 50% of the hear ts from normal (sham) rats and 89% of the hypertrophied hearts from ao rtic-banded (band) rats (P<.01 versus sham) exhibited VF. Phosphocreat ine content was significantly higher in sham than band hearts during c ontrol perfusion (53.3+/-1.6 versus 39.8+/-2.0 mu mol/g dry wt)/. Befo re VF at 20 minutes of ischemia, Na-i(+) accumulation was greater in h earts 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 depleti on was also greater for VF hearts in the sham group. Infusion of the N a+-H+ exchange inhibitor 5-(N,N-hexamethylene)-amiloride prevented VF in sham and band hearts; reduced Na-i(+) accumulation but similar PIEP depiction were observed compared with VF hearts before the onset of V F. Rapid changes in Na-i(+), pH(i), and HEP began with VF, resulting i n intracellular Na-i(+), overload (approximate to 300% of control) and increased HEP depletion. A delayed postischemic functional recovery o ccurred in VF hearts, which correlated temporally with the recovery of Na-i(+). In conclusion, alterations in Na-i(+) were associated with s pontaneous VF transitions, consistent with involvement of excess Na-i( +), accumulation in VF initiation and maintenance and with previously reported alterations in Ca-i(2+) with VF. Hypertrophied band hearts ex hibited enhanced susceptibility to ischemia-induced VF, possibly linke d to a lower HEP reserve.