Faculty Collaboration Database

Inhibition of Na(+)/H(+) isoform-1 exchange protects hearts perfused after 6-hour cardioplegic cold storage. J Heart Lung Transplant 2002 Mar;21(3):374-82

Date

03/19/2002

Pubmed ID

11897527

DOI

10.1016/s1053-2498(01)00383-7

Scopus ID

2-s2.0-0036125863 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

OBJECTIVES: 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.

Author List

Stowe DF, Heisner JS, An J, Camara A, Varadarajan SG, Novalija E, Chen Q, Schelling P

Author

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bicarbonates
Calcium Chloride
Cardioplegic Solutions
Coronary Circulation
Guanidines
Guinea Pigs
Heart
Heart Rate
Magnesium
Myocardial Reperfusion Injury
Potassium Chloride
Random Allocation
Sodium Chloride
Sodium-Hydrogen Exchangers
Sulfones