Na+/H+ exchange inhibition improves long-term myocardial preservation.
BACKGROUND
Na+/H+ exchange plays an important role in the ionic changes observed during myocardial ischemia and reperfusion. We investigated the cardioprotective efficacy of a selective Na+/H+ exchange inhibitor, 4-isopropyl-3-methylsulfonyl-benzoylguanidin-methanesulfonate (HOE642), in a canine model of long-term heart preservation.


METHODS
Canine donor hearts were stored for 24 hours in hyperkalemic crystalloid cardioplegic solution; in cardioplegic solution enriched with HOE642; in cardioplegic solution enriched with HOE642, with donor and recipient treated with HOE642; in standard cardioplegic solution, with donor and recipient treated with HOE642; or in standard cardioplegic solution, with only the recipient treated. After orthotopic transplantation, pressure-volume relationships were obtained and dogs were weaned from bypass. Morphology was studied.


RESULTS
Myocardial compliance was well preserved when donor and recipient were treated. These groups had the lowest myocardial water content, and no morphologic signs of irreversible damage. In these groups, weaning from cardiopulmonary bypass was successful in 10 of 10 animals, with a cardiac index around 2 L x min(-1) x m(-2). Only 3 of 5 animals in each of the other three groups could be weaned, with significantly lower cardiac indices.


CONCLUSIONS
Treatment with HOE642 in both donor and recipient improves myocardial compliance, postweaning cardiac index, and ultrastructure of donor hearts preserved for 24 hours and orthotopically transplanted.
Kim
Y I
YI
Center for Experimental Surgery and Anaesthesiology, and Department of Pathology, Katholieke Universiteit Leuven, Belgium.
Herijgers
P
P
Laycock
S K
SK
Van Lommel
A
A
Verbeken
E
E
Flameng
W J
WJ
D000818:Animals; D002314:Cardioplegic Solutions; D002315:Cardiopulmonary Bypass; D004285:Dogs; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000502:physiology*; D016027:Heart Transplantation; D006859:Hydrogen / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D009926:Organ Preservation / Q000379:methods*; D009929:Organ Size; D012964:Sodium / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology*; D016277:Ventricular Function, Left
D002314:Cardioplegic Solutions; D006146:Guanidines; D013450:Sulfones; C093373:cariporide; D006859:Hydrogen; D012964:Sodium