Combined blockade of the Na+ channel and the Na+/H+ exchanger virtually prevents ischemic Na+ overload in rat hearts.
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.
ten Hove
Michiel
M
Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Jansen
Maurits A
MA
Nederhoff
Marcel G J
MG
Van Echteld
Cees J A
CJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000633:toxicity*; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology
D006146:Guanidines; D010710:Phosphates; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C118397:eniporide; D008012:Lidocaine; D012964:Sodium