Signal Transduction of Opioid-induced Cardioprotection in Ischemia-Reperfusion

Abstract

Stimulation of delta1-opioid receptors generates oxygen radicals via mitochondrial KATP channels. This signaling pathway attenuates oxidant stress and cell death in cardiomyocytes.

Cardioprotective effects of anesthetic preconditioning in rats with ischemia-reperfusion injury: propofol versus isoflurane

“…Radicals are released from the mitochondria as a consequence of K ATP channel opening (Duranteau et al, 1998;Kowaltowski et al, 2001;McPherson and Yao, 2001a). Activation of opiate receptors by morphine leads to activation of mitochondrial K ATP channels followed by an increase of intracellular free radical formation (McPherson and Yao, 2001a;2001b). Furthermore, protein kinase C can be activated by free radicals (Gopalakrishna and Anderson, 1989).…”

Inibição da corrente de cálcio tipo L por tramadol e enantiômeros em miócitos cardíacos de ratos

“…The effects of morphine on ionic currents in cardiac myocytes have shown not to depend on opioid receptor 24 or to be mediated via d-and k-receptors 25 . However, its cardioprotective effect is known to be due to the activation of d-receptors 26,27 . Studies have shown that opioids like dextropropoxiphene, pethidine and leucine enkephalin reduce I Ca-L but only the inhibition induced by d-receptor agonist (leucine enkephalin) was blocked by naloxone 28,29 .…”

Myocardial protection by anesthetic agents against ischemia-reperfusion injury: An update for anesthesiologists

“…Intravenous administration of 3 mg morphine after the onset of myocardial infarction reduced the serum ICAM-1 level. 90 However it is of note that there have been reports which showed that halogenated anesthetics 43 and opioids 83 were not protective when administered after the onset of ischemia. Overall, it is still controversial whether anesthetics protect the heart when administered after the onset of ischemia.…”

“…Conversely protection by morphine and fentanyl is abolished by *-antagonists. 64,67,78,83 The role of 6-receptors remains controversial. 75,86,88,89 Whether µ-receptors contribute to cardioprotection in humans is not known.…”

“…The beneficial effects were eliminated by a G i protein inhibitor, 81 a PKC inhibitor, 62,67,85,86 and a selective mitochondrial K ATP channel blocker. 63,66,70,76,82,83,85,86 The effect of "classic" or "early" ischemic preconditioning is transient and lost within 0.5-2 hr after brief ischemic episodes, but the protection exhibits a biphasic time course and returns after 24 hr. 20,22 This late protection is called "late", "delayed" or "second window" preconditioning.…”