Morphine Mimics Preconditioning via Free Radical Signals and Mitochondrial K _ATP Channels in Myocytes

Abstract

These results suggest that direct stimulation of cardiocyte opioid delta(1) receptors leads to activation of mitochondrial K(ATP) channels. The resultant increase of intracellular free radical signals may be an important component of the signaling pathways by which morphine mimics preconditioning in cardiomyocytes.

Anesthetic-induced myocardial protection in cardiac surgery: relevant mechanisms and clinical translation

“…Volatile anesthetics attenuate the degradation of the endothelial glycocalyx layer following I-R injury [19], the integrity of which plays a vital role in preventing leukocyte and platelet adhesion thereby mitigating inflammation and tissue edema [20]. and volatile anesthetic induced pre-conditioning [24]. In addition, opioids have post-conditioning effects when administered in close proximity to reperfusion [25].…”

“…Regarding the use of propofol-based TIVA, it is important to note that its oxygen free radical scavenging property may actually prevent other pre-conditioning effects [16,24]. Indeed, one of the triggers of anesthetic pre-conditioning is the formation of ROS species that can be inhibited by propofol.…”

Redox Signaling Pathways Involved in Neuronal Ischemic Preconditioning

“…In contrast to excessive ROS generated by ischemia/reperfusion, there is evidence that mild amounts of ROS production are protective and may serve as a trigger for activating IPC protective pathways [35][36][37][38][39]. For example, perfusing the isolated heart with the antioxidant Nacetylcysteine abolished IPC induced cardioprotection [40].…”

“…In both the brain [44] and heart [45] opening of the mitoK + ATP channels occurs early in the preconditioning response and is required for IPC protection. The use of a mitoK + ATP channel antagonist, such as 5-hydroxydecanoic acid, blocked IPC-mediated protection in the rat heart [46] whereas the mitoK + ATP channel agonist, diazoxide, induced a preconditioning response [38,47,48]. The opening of the mitoK + ATP channel has been suggested to lead to generation of ROS.…”

Morphine use in elderly patients with acute heart failure

“…However, several studies have been published in which a role of opioid receptors in morphine induced acute and delayed preconditioning was confirmed (Chen et al, 2008;Frassdorf et al, 2010;Gintzler and Chakrabarti, 2006;Jiang et al, 2006;McPherson and Yao, 2001;Peart et al, 2005;Shi et al, 2003;Zuurbier et al, 2005). In addition, cardioprotective effect of chronic morphine exposure has also been observed in a mouse model of myocardial infarction (Peart and Gross, 2004;Peart et al, 2011).…”