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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

✍ Scribed by Gil Navon; Jeffrey G. Werrmann; Ron Maron; Sheila M. Cohen


Publisher
John Wiley and Sons
Year
1994
Tongue
English
Weight
920 KB
Volume
32
Category
Article
ISSN
0740-3194

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✦ Synopsis


Abstract

The triple quantum filtered ^23^Na 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 τ 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 μ significantly inhibited (P < 0.01) the influx of intracellular Na^+^ during 20 min of ischemia at 36.2°C in this rat heart model. In parallel^31^P NMR studies, EIPA had no effect on either the development of acidosis during ischemia or on the recovery of pH, 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.


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## Abstract Multiple‐quantum filtered (MQF) NMR offers the possibility of monitoring intracellular (IC) Na content in the absence of shift reagents (SR), provided that (i) the contribution from IC Na to the MQF spectrum is substantial and responds to a change in IC Na content, and (ii) the amplitud