Both Na+-K+ ATPase and Na+-H+ exchanger are immediately active upon post ischemic reperfusion in isolated rat hearts

Limited time resolution has hampered proper evaluation of changes in intracellular Na+ (Na-i(+)) in whole hearts upon post-ischemic reperfusion. In isolated rat hearts perfused at 37 degrees C, we studied the contribution of the Na+-K+ ATPase and the Na+-H+ exchanger to control of Na+, during reperfusion using Na-23 NMR and the shift reagent Tm(DOTP)(5-) with a time resolution of 5 s. To assess activities of the Na+-K+ ATPase and the Na+-H+ exchanger, 250 mu mol/l ouabain and/or 3 mu mol/l EIPA, respectively, was added to the perfusate during the first 5 min of reperfusion, following 20 min of ischemia. When used, ouabain was also present for 2 min prior to ischemia. Na-i(+) increased during ouabain perfusion prior to ischemia (132 +/- 5 and 133 +/- 4% of the pre-ischemic control value after 2 min, in ouabain and ouabain + EIPA hearts, respectively; mean +/- S.E.M,; n = 6 per group) resulting in higher end-ischemic Values in ouabain and ouabain + EIPA hearts (249 +/- 9 and 267 +/- 17% of the pre-ischemic control value, respectively) than in control and EIPA hearts (207 +/- 21 and 199 +/- 10% of the pre-ischemic control value, respectively). In ouabain, hearts Na-i(+) started to rise directly upon reperfusion and amounted to 117 +/- 6% of the end-ischemic value after 60 s of reperfusion. In control hearts, however, Na-i(+), dropped immediately and was 87 +/- 5% of the end-ischemic value after 60 s, indicating that the Na+-K+ ATPase resumed function directly upon reperfusion. The initial steep increase of Na-i(+) upon reperfusion in ouabain hearts, which diminished after similar to 40 s to the rate of increase observed during ischemia, was absent in ouabain + EIPA hearts. This indicates the existence, although masked by Na+-K+ ATPase activity, of a Na+-H+ exchange mediated Na+ influx upon reperfusion, If only EIPA was present during reperfusion the initial decrease in Na-i(+) was faster than in control hearts, corroborating this finding. (C) 1998 Academic Press Limited.