EXPERIMENTAL STUDY
Delta opioid receptor stimulation mimics ischemic preconditioning in human heart muscle
Sam P. Bell, BSc, MBBS*,
Michael N. Sack, PhD, MBBCh ,
Asha Patel, HND*,
Lionel H. Opie, MD, DPhil, FRCP and
Derek M. Yellon, DSc, MRCP, FESC, FACC*
* The Hatter Institute, University College London Hospitals and Medical School, London, United Kingdom
The Hatter Institute, Cape Heart Center, University of Cape Town, Cape Town, South Africa
Manuscript received March 13, 2000;
revised manuscript received July 6, 2000,
accepted August 16, 2000.
Reprint requests and correspondence: Professor Derek M. Yellon, The Hatter Institute, University College Hospital, Grafton Way, London WC1E 6DB, United Kingdom
hatter-institute{at}ucl.ac.uk
OBJECTIVES
The objective of this study was to examine whether the delta ( ) opioid receptor isoform is expressed in the human heart and whether this receptor improves contractile function after hypoxic/reoxygenation injury.
BACKGROUND
Delta opioid receptor agonists mimic preconditioning (PC) in rat myocardium, corresponding to known cardiac opioid receptor expression in this species.
METHODS
The messenger RNA transcript encoding the opioid receptor was identified in human atria and ventricles. To evaluate the cardioprotective role of the opioid receptor, human atrial trabeculae from patients undergoing coronary bypass grafting were isolated and superfused with Tyrode’s solution. A control group underwent 90 min of simulated ischemia and 120 min of reoxygenation. A second group was preconditioned with 3 min simulated ischemia and 7 min reoxygenation. Additional groups included: superfusion with the receptor agonist (DADLE) (10 nM), with the receptor antagonist naltrindole (10 nM) and with the mitochondrial KATP channel blocker 5-hydroxydecanoate (5HD) (100 µM) either with or without PC, respectively. A final group was superfused with 5HD before DADLE. The end point used was percentage of developed force after 120 min of reoxygenation.
RESULTS
Results, expressed as means ± SEM, were: control = 32.6 ± 3.8%; PC = 50.5% ± 1.8*; DADLE = 46.0 ± 3.9%*; PC + naltrindole = 25.5 ± 3.9%; naltrindole alone = 25.5 ± 4.3%; 5HD + PC = 28.9 ± 7.4%; 5HD alone = 24.1 ± 3.0%; 5HD + DADLE = 26.9 ± 4.4% (*p < 0.001 vs. controls).
CONCLUSIONS
Human myocardium expresses the opioid receptor transcript. Stimulation of this receptor appears to protects human muscle from simulated ischemia, similar to PC, and via opening of the mitochondrial KATP channel.
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Abbreviations and Acronyms
| | DADLE | = delta opioid agonist | | naltrindole + PC | = naltrindole plus preconditioning | | PC | = preconditioning | | PCR | = polymerase chain reaction | | 5HD | = 5-hydroxydecanoate |
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