Anaesthetics and cardiac preconditioning. Part I. Signalling and cytoprotective mechanisms.
Cardiac preconditioning represents the most potent and consistently reproducible method of rescuing heart tissue from undergoing irreversible ischaemic damage. Major milestones regarding the elucidation of this phenomenon have been passed in the last two decades. The signalling and amplification cascades from the preconditioning stimulus, be it ischaemic or pharmacological, to the putative end-effectors, including the mechanisms involved in cellular protection, are discussed in this review. Volatile anaesthetics and opioids effectively elicit pharmacological preconditioning. Anaesthetic-induced preconditioning and ischaemic preconditioning share many fundamental steps, including activation of G-protein-coupled receptors, multiple protein kinases and ATP-sensitive potassium channels (K(ATP) channels). Volatile anaesthetics prime the activation of the sarcolemmal and mitochondrial K(ATP) channels, the putative end-effectors of preconditioning, by stimulation of adenosine receptors and subsequent activation of protein kinase C (PKC) and by increased formation of nitric oxide and free oxygen radicals. In the case of desflurane, stimulation of alpha- and beta-adrenergic receptors may also be of importance. Similarly, opioids activate delta- and kappa-opioid receptors, and this also leads to PKC activation. Activated PKC acts as an amplifier of the preconditioning stimulus and stabilizes, by phosphorylation, the open state of the mitochondrial K(ATP) channel (the main end-effector in anaesthetic preconditioning) and the sarcolemmal K(ATP) channel. The opening of K(ATP) channels ultimately elicits cytoprotection by decreasing cytosolic and mitochondrial Ca(2+) overload.
D000222:Adaptation, Physiological; D000255:Adenosine Triphosphate / Q000378:metabolism; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D020555:GTP-Binding Protein Regulators / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000777:Anesthetics; D020555:GTP-Binding Protein Regulators; D015221:Potassium Channels; D011957:Receptors, Opioid; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D011493:Protein Kinase C