Background. Na+/H+ exchange plays an important role in the ionic chang
es observed during myocardial ischemia and reperfusion. We investigate
d the cardioprotective efficacy of a selective Na+/H+ exchange inhibit
or, -3-methylsulfonyl-benzoylguanidin-methanesulfonate (HOE642), in a
canine model of long-term heart preservation. Methods. Canine donor he
arts were stored for 24 hours in hyperkalemic crystalloid cardioplegic
solution; in cardioplegic solution enriched with HOE642; in cardiople
gic solution enriched with HOE642, with donor and recipient treated wi
th 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-volu
me relationships were obtained and dogs were weaned from bypass. Morph
ology was studied. Results. Myocardial compliance was well preserved w
hen donor and recipient were treated. These groups had the lowest myoc
ardial water content, and no morphologic signs of irreversible damage.
In these groups, weaning from cardiopulmonary bypass was successful i
n 10 of 10 animals, with a cardiac index around 2 L.min(-). m(-2). Onl
y 3 of 5 animals in each of the other three groups could be weaned, wi
th significantly lower cardiac indices. Conclusions. Treatment with HO
E642 in both donor and recipient improves myocardial compliance, postw
eaning cardiac index, and ultrastructure of donor hearts preserved for
24 hours and orthotopically transplanted. (C) 1998 by The Society of
Thoracic Surgeons.