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, pHi, 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 mumol/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, pHi, and HEP began with VF, resulting in intracellular Na+i overload (approximately 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Pike
M M
MM
Department of Medicine, University of Alabama at Birmingham, USA.
Luo
C S
CS
Yanagida
S
S
Hageman
G R
GR
Anderson
P G
PG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D004734:Energy Metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000378:metabolism; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D012975:Sodium Isotopes; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism*
D007773:Lactates; D010759:Phosphorus Isotopes; D012975:Sodium Isotopes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D012964:Sodium