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+i during reperfusion using 23Na 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 micro mol/l ouabain and/or 3 micro 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 approximately 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.
Van Emous
J G
JG
Interuniversity Cardiology Institute of The Netherlands and Department of Cardiology, Heart Lung Institute, University Hospital, Utrecht, The Netherlands.
Schreur
J H
JH
Ruigrok
T J
TJ
Van Echteld
C J
CJ
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D017923:Sodium-Hydrogen Exchangers; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; C039614:ethylisopropylamiloride