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

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.

Role of CaMKII in post acidosis arrhythmias: A simulation study using a human myocyte model

“…A similar DAD Na + dependence was also observed with increased PF (Fig. 5B), in line with studies indicating elevated Na + -induced arrhythmia occurrence [51][52][53].…”

Sodium alterations in isolated rat heart during cardioplegic arrest

“…NMR provides a unique opportunity for the measurement of [Na 1 ] i in a rat heart by using shift reagents (3,47,15,25,26,(31)(32)(33)47) or by using a shift reagent in combination with multiple-quantum filtering (20,27,28,36). Despite the many advantages of using a shift reagent, limitations are inevitable.…”

Cariporide for Pharmacologic Defibrillation After Prolonged Cardiac Arrest

“…The mechanism of spontaneous defibrillation in cariporide-treated animals is as yet unclear. Intracellular Na+ accumulation (31), intracellular Ca++ overload (32,33), and the depletion of myocardial adenosine triphosphate (ATP) (34) during prolonged untreated VF had been shown to be associated with increases in the defibrillation threshold. The capability of cariporide to mitigate increases in intracellular Na+ and Ca++ could explain the mechanism.…”