Inhibition of Na(+)/H(+) isoform-1 exchange protects hearts perfused after 6-hour cardioplegic cold storage.
OBJECTIVE
Cardiac ischemia-reperfusion activates Na(+)/H(+) exchange; excess Na(+) and the resulting Ca(2+) overload, through reverse Na(+)/Ca(2+) exchange, cause cellular injury and cardiac dysfunction. We postulated that inhibiting the Na(+)/H(+) isoform-1 exchanger would add to the protection of hearts after long-term cold storage in acidic cardioplegic solution.


METHODS
Guinea pig hearts were isolated and perfused at 37 degrees C with Krebs-Ringer's solution (KRS) and then switched to an acidic St. Thomas solution (STS) at 25 degrees C. Perfusion was stopped at 10 degrees C, and hearts were stored for 6 hours in STS at 3.4 degrees C. On reperfusion to 25 degrees C, hearts were perfused with KRS for 60 minutes. Hearts were divided into 4 groups: sham control (SHAM); eniporide (EPR, EMD96785) IV, 1 mg/kg given IV over 15 minutes before heart isolation; EPR intracoronary, 1 micromol/liter in STS given intracoronary after heart isolation; and EPR IV and intracoronary.


RESULTS
Values at 60 minutes reperfusion (the percentage of control [100%] before cold storage) are given, respectively, for EPR IV, EPR intracoronary, and EPR IV and intracoronary vs drug-free SHAM (SEM, *p < 0.05 vs SHAM): 72% +/- 3%*, 65% +/- 3%*, and 81% +/- 2%* vs 55% +/- 3% for left ventricular pressure; 94% +/- 3%*, 96% +/- 5%*, and 102% +/- 2%* vs 81% +/- 3% for coronary flow; 60% +/- 2%, 58% +/- 3%, and 74%* +/- 3% vs 58% +/- 4% for cardiac efficiency; 106% +/- 2%*, 108% +/- 3%*, and 107% +/- 2%* vs 116% +/- 4% for percentage of O(2) extraction. Infarct size as percentage of ventricular weight was 20% +/- 3%*, 31% +/- 3%, and 6% +/- 2%* vs 35% +/- 3% (SHAM) after 60 minutes of reperfusion.


CONCLUSIONS
Na(+)/H(+) isoform-1 exchanger inhibition, particularly if given IV before storage and intracoronary during cooling and rewarming, adds to the protection of cardioplegic solutions.
Stowe
David F
DF
Department of Anesthesiology Research Laboratories, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. dfstowe@mcw.edu
Heisner
James S
JS
An
Jianzhong
J
Camara
Amadou
A
Varadarajan
Srinivasan G
SG
Novalija
Enis
E
Chen
Qun
Q
Schelling
Pierre
P
D000818:Animals; D001639:Bicarbonates; D002122:Calcium Chloride; D002314:Cardioplegic Solutions; D003326:Coronary Circulation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008274:Magnesium; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011189:Potassium Chloride; D011897:Random Allocation; D012965:Sodium Chloride; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use
D001639:Bicarbonates; D002314:Cardioplegic Solutions; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; C041711:St. Thomas' Hospital cardioplegic solution; D013450:Sulfones; D012965:Sodium Chloride; D011189:Potassium Chloride; C118397:eniporide; D008274:Magnesium; D002122:Calcium Chloride