Opioids and cardioprotection

Opioid peptides and exogenous opioids such as morphine are known to exert important cardiovascular effects. However, until recently, it was not appreciated that activation of specific receptors results in a potent cardioprotective effect to reduce infarct size in experimental animals and to reduce cell death in isolated cardiomyocytes. In intact rat and rabbit hearts, nonselective opioid receptor antagonists such as naloxone and a selective delta (1)-opioid receptor antagonist, 7-benzylidenenaltrexone, have been shown to inhibit the cardioprotective effect of ischemic preconditioning, a phenomenon in which brief periods of ischemia protect the heart against a more prolonged period of ischemia. Selective delta (1) specific agonists such as 2-methyl-4a-alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a-alpha -octahydroquinolino[2,3,3-g]isoquinoline have been shown to exert potent cardioprotective effects in intact animals and cardiac myocytes via activation of G(i/o) proteins, protein kinase C, and ultimately, the mitochondrial K-ATP channel. These protective effects occur immediately following drug administration, and reappear 24-48 hr post treatment. Although further studies are needed to more clearly define the mechanisms by which opioids exert their cardioprotective effects, the data accumulated and summarized in this review suggest that this class of drugs mag. not only be useful in alleviating the pain associated with a myocardial infarction, but may also be simultaneously reducing the size of the ultimate infarct. Since many of these drugs are already clinically available, a long period of drug development may not be necessary before the use of these drugs reaches the patient with signs of myocardial ischemia. (C) 2001 Elsevier Science Inc. All rights reserved.