The Role of the Na+Channel in the Accumulation of Intracellular Na+During Myocardial Ischemia: Consequences for Post-ischemic Recovery

To further elucidate the role of the Na+channel in the ischemic accumulation of intracellular Na+(Na+i), 200μ lidocaine was included in the perfusate for 5 min prior to 30 min of ischemia in isolated rat hearts paced at 5 Hz. Na+iand high-energy phosphates were measured, using23Na-NMR with the shift reagent TmDOTP5−and31P-NMR, respectively. Control values of phosphocreatine (PCr) and ATP were 14.1±1.5 m and 7.7±0.7 m , respectively (all data: mean± ). During lidocaine perfusion the rate pressure product (RPP) decreased by approximately 50% and Na+ideclined from 11.5±1.5 m to 9.8±2.1 m . During ischemia Na+iin lidocaine hearts rose to 17.9±2.5 m v28.4±1.7 m in control hearts (P<0.05). In hearts in which extracellular Ca2+was lowered prior to ischemia to reach a similar RPP decrease as in lidocaine hearts, Na+irose to 26.3±3.0 m during ischemia (P<0.05vlidocaine, v control). Lidocaine did not affect the decline of PCr during ischemia (to 0.5±0.5v0.7±0.8 m in lidocaine and control hearts, respectively) but significantly attenuated the initial decrease of pHi(6.06±0.07v5.76±0.04 after 20 min,P<0.01), attenuated the initial decline of ATP (3.3±1.3v1.5±0.9 m after 20 min,P<0.05) and delayed the time to onset of contracture. However, at the end of ischemia pHi(5.73±0.04 and 5.78±0.05) and ATP (1.2±0.6 and 0.9±0.8 m ) were not significantly different. At 30 min of reperfusion Na+iwas 14.9±2.6 m in lidocaine heartsv20.0±3.1 m in controls. PCr (9.6±2.3v4.9±0.9 m ,P<0.05) and ATP (3.0±0.6v1.8±0.6 m ) recovered better in lidocaine hearts. Furthermore, developed and end-diastolic pressure recovered better in lidocaine hearts. In conclusion, Na+influx during ischemia occurs, at least partly, via the Na+channels, and blocking this channel during ischemia improves post-ischemic functional and metabolic recovery.