31P NMR and triple quantum filtered 23Na NMR studies of the effects of inhibition of Na+/H+ exchange on intracellular sodium and pH in working and ischemic hearts.
The triple quantum filtered 23Na NMR method is applied here to measure the effects of EIPA, a specific inhibitor of the Na+/H+ antiporter, on relative intracellular sodium concentrations in isolated working hearts at baseline, during ischemia, and at subsequent reperfusion. In analogy to the spectrophotometric isosbestic point, an approach is developed that defines a value of tau at which the effect of the relaxation times on the TQF signal intensities is minimized, and the signals are proportional to the sodium concentration for both ischemic and working hearts. EIPA at 1.5 microM significantly inhibited (P < 0.01) the influx of intracellular Na+ during 20 min of ischemia at 36.2 degrees C in this rat heart model. In parallel 31P NMR studies, EIPA had no effect on either the development of acidosis during ischemia or on the recovery of pHi during reperfusion despite its profound effect on intracellular Na+ influx. Thus, under our conditions the Na+/H+ antiporter did not play a critical role in the maintenance of intracellular pH. EIPA treatment resulted in improved recovery (P < 0.005) of mechanical function after 20 min of ischemia. [ATP] was higher in treated hearts during ischemia and reperfusion.
Navon
G
G
Merck Research Laboratories, Rahway, NJ 07065.
Werrmann
J G
JG
Maron
R
R
Cohen
S M
SM
D000138:Acidosis / Q000209:etiology / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010759:Phosphorus Isotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects*; D012975:Sodium Isotopes
D010759:Phosphorus Isotopes; D015222:Sodium Channels; D012975:Sodium Isotopes; D000584:Amiloride; D006859:Hydrogen; D012964:Sodium; C039614:ethylisopropylamiloride