(Circulation. 1999;99:3079-3085.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Opening of Potassium Channels
The Common Cardioprotective Link Between Preconditioning and Natural Hibernation?
From the Department of Physiology (E.K.), Kaunas Medical University, Lithuania, and the Departments of Cardiovascular Surgery, Biochemistry and INSERM U-127 (J.P., C.M., J.-M.L., P.M.), Hôpital Lariboisière, Paris, France.
Correspondence to Philippe Menasché, MD, PhD, Department of Cardiovascular Surgery, Hôpital Lariboisière, 2, rue Ambroise Paré, 75475 Paris Cedex 10, France.
Background—The tolerance of
hibernating mammals to cold hypoxia is related to a factor
similar to agonists of 
-opioid receptors. This study was designed to
assess whether activation of these receptors could reproduce the
protection conferred by ischemic preconditioning and whether
such cardioprotection was similarly mediated by an opening of
ATP-sensitive potassium (KATP) channels.
Methods and Results—Thirty-two isolated rat hearts were arrested
with and stored in Celsior at 4°C for 5 hours before being reperfused
for 2 hours. They were divided into 4 equal groups. Group 1 hearts
served as controls. In group 2, ischemic preconditioning was
elicited by two 5-minute global ischemia periods interspersed
with 5 minutes of reperfusion before arrest. In group 3, hearts were
pharmacologically preconditioned with a 15-minute infusion of the
-opioid receptor agonist
D-Ala2-D-Leu5-enkephalin (DADLE; 200
µmol/L). In group 4, the protocol was similar to group 3 except that
infusion of DADLE was preceded by infusion of the KATP
blocker glibenclamide (50 µmol/L). The salutary effects of both
forms of preconditioning were primarily manifest as a better
preservation of diastolic function, a reduced myocardial
edema, and reduced creatine kinase leakage. This protection was
abolished by administration of glibenclamide before DADLE.
Conclusions—These data suggest that activation of -opioid
receptors improves recovery of cold-stored hearts to a similar extent
as ischemic preconditioning, most likely through an opening of
KATP channels. This provides a rationale for improving the
preservation of hearts for transplantation by pharmacologically
duplicating the common pathway to natural hibernation and
preconditioning.
Key Words: transplantation • ischemia • potassium • receptors
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