Combined blockade of the Na+ channel and the Na+/H+ exchanger virtually prevents ischemic Na+ overload in rat hearts

Michiel ten Hove, Maurits A Jansen, Marcel G J Nederhoff, Cees J A Van Echteld

Research output: Contribution to journalArticlepeer-review

Abstract

Blocking either the Na(+) channel or the Na(+)/H(+) exchanger (NHE) has been shown to reduce Na(+) and Ca(2+) overload during myocardial ischemia and reperfusion, respectively, and to improve post-ischemic contractile recovery. The effect of combined blockade of both Na(+) influx routes on ionic homeostasis is unknown and was tested in this study. [Na(+)](i), pH(i) and energy-related phosphates were measured using simultaneous (23)Na- and (31)P-NMR spectroscopy in isolated rat hearts. Eniporide (3 muM) and/or lidocaine (200 muM) were administered during 5 min prior to 40 min of global ischemia and 40 min of drug free reperfusion to block the NHE and the Na(+) channel, respectively. Lidocaine reduced the rise in [Na(+)](i) during the first 10 min of ischemia, followed by a rise with a rate similar to the one found in untreated hearts. Eniporide reduced the ischemic Na(+) influx during the entire ischemic period. Administration of both drugs resulted in a summation of the effects found in the lidocaine and eniporide groups. Contractile recovery and infarct size were significantly improved in hearts treated with both drugs, although not significantly different from hearts treated with either one of them.

Original languageEnglish
Pages (from-to)101-110
Number of pages10
JournalMolecular and Cellular Biochemistry
Volume297
Issue number1-2
DOIs
Publication statusPublished - Mar 2007

Keywords

  • Animals
  • Blood Pressure
  • Guanidines
  • Heart
  • Heart Rate
  • Hydrogen-Ion Concentration
  • Lidocaine
  • Magnetic Resonance Spectroscopy
  • Male
  • Myocardial Contraction
  • Myocardial Infarction
  • Myocardial Ischemia
  • Myocardial Reperfusion
  • Phosphates
  • Rats
  • Rats, Wistar
  • Sodium
  • Sodium Channel Blockers
  • Sodium Channels
  • Sodium-Hydrogen Antiporter
  • Sulfones

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