Early reperfusion levels of Na(+) and Ca(2+) are strongly associated with postischemic functional recovery but are disassociated from K(ATP) channel-induced cardioprotection.
We previously demonstrated that pinacidil does not affect Na(+)(i) accumulation, cellular energy depletion, or acidosis during myocardial ischemia, but dramatically improves the cationic/energetic status during reperfusion. We investigated the role of this latter effect in K(ATP) channel-induced cardioprotection. Employing (23)Na and (31)P nuclear magnetic resonance spectroscopy with perfused rat hearts, reperfusion Na(+)(i) was altered with brief infusions of ouabain and/or RbCl to transiently decrease or increase Na(+)/K(+) ATPase activity. The increases and decreases in functional recovery (%LVDP-R) with pinacidil or ouabain, respectively, were largely unaltered by each other's presence. Early reperfusion Na(+)(i) and cellular energy were greatly altered by ouabain and indicated linear relationships with %LVDP-R. Pinacidil shifted these relationships to higher %LVDP-R. Increasing early reperfusion Na(+)(i) decreased %LVDP-R but did not diminish pinacidil's capacity to improve %LVDP-R. Approximately 75% and 45% of the pinacidil-induced improvements in %LVDP-R, could be disassociated from early reperfusion Na(+)(i) and cellular energy, respectively. Both pinacidil and RbCl infusion blunted ouabain's elevation of reperfusion Na(+)(i), but RbCl did not improve %LVDP-R. Atomic absorption tissue Ca(2+) measurements indicated that pinacidil reduced late reperfusion Ca(2+) uptake, but did not reduce early reperfusion Ca(2+), and its beneficial effects were resistant to ouabain-induced early reperfusion Ca(2+) increases. In conclusion, K(ATP) channel-induced cardioprotection does not require moderation of Na(+)(i) accumulation, cellular energy depletion, or acidosis during ischemia. K(ATP) channel-induced cardioprotection is largely independent of the accelerated reperfusion Na(+)(i) recovery it induces and does not require early reperfusion reductions of tissue Ca(2+). A larger role for early reperfusion cellular energy cannot be excluded.
Takayama
Eiichi
E
Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Room 308, Zeigler Research Building, 703, 19th Street South, Birmingham, AL 35294-0007, USA.
Guo
Ling-Ling
LL
Digerness
Stanley B
SB
Pike
Martin M
MM
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D010042:Ouabain / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000494:pharmacology; D012964:Sodium / Q000032:analysis / Q000378:metabolism*; D016276:Ventricular Function
D002712:Chlorides; D008565:Membrane Proteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D010042:Ouabain; D011189:Potassium Chloride; D020110:Pinacidil; D012964:Sodium; D012413:Rubidium; C032710:rubidium chloride; D002118:Calcium