Mm. Pike et al., NA-23 AND P-31 NUCLEAR-MAGNETIC-RESONANCE STUDIES OF ISCHEMIA-INDUCEDVENTRICULAR-FIBRILLATION - ALTERATIONS OF INTRACELLULAR NA-ENERGY( AND CELLULAR), Circulation research, 77(2), 1995, pp. 394-406
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.