title: The role of the Na+ channel in the accumulation of intracellular Na+ during myocardial ischemia: consequences for post-ischemic recovery.
abstract: To further elucidate the role of the Na+ channel in the ischemic accumulation of intracellular Na+ (Na+i), 200 microM lidocaine was included in the perfusate for 5 min prior to 30 min of ischemia in isolated rat hearts paced at 5 Hz. Na+i and high-energy phosphates were measured, using 23Na-NMR with the shift reagent TmDOTP5- and 31P-NMR, respectively. Control values of phosphocreatine (PCr) and ATP were 14.1 +/- 1.5 mM and 7.7 +/- 0.7 mM, respectively (all data: mean +/- S.D.). During lidocaine perfusion the rate pressure product (RPP) decreased by approximately 50% and Na+i declined from 11.5 +/- 1.5 mM to 9.8 +/- 2.1 mM. During ischemia Na+i in lidocaine hearts rose to 17.9 +/- 2.5 mM v 28.4 +/- 1.7 mM 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+i rose to 26.3 +/- 3.0 mM during ischemia (P<0.05 v lidocaine, N.S. v control). Lidocaine did not affect the decline of PCr during ischemia (to 0.5 +/- 0.5 v 0.7 +/- 0.8 mM in lidocaine and control hearts, respectively) but significantly attenuated the initial decrease of pH(i) (6.06 +/- 0.07 v 5.76 +/- 0.04 after 20 min, P<0.01), attenuated the initial decline of ATP (3.3 +/- 1.3 v 1.5 +/- 0.9 mM after 20 min, P<0.05) and delayed the time to onset of contracture. However, at the end of ischemia pH(i) (5.73 +/- 0.04 and 5.78 +/- 0.05) and ATP (1.2 +/- 0.6 and 0.9 +/- 0.8 mM) were not significantly different. At 30 min of reperfusion Na+i was 14.9 +/- 2.6 mM in lidocaine hearts v 20.0 +/- 3.1 mM in controls. PCr (9.6 +/- 2.3 v 4.9 +/- 0.9 mM, P<0.05) and ATP (3.0 +/- 0.6 v 1.8 +/- 0.6 mM) 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.
authors.affiliation: Department of Cardiology, Heart Lung Institute, University Hospital, Utrecht, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: van Emous
authors.forename: M G
authors.initials: MG
authors.lastname: Nederhoff
authors.forename: T J
authors.initials: TJ
authors.lastname: Ruigrok
authors.forename: C J
authors.initials: CJ
authors.lastname: van Echteld
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D008012:Lidocaine / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000628:therapy*; D015425:Myocardial Reperfusion; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D008012:Lidocaine; D012964:Sodium