title: Signal transduction mechanisms in the ischemic and reperfused myocardium.
abstract: The cellular mechanisms regulating myocardial dysfunction during ischemia and subsequent reperfusion are complex. As can be determined from this review, it is clear that signal transduction pathways are altered during these conditions, which may explain, in part, the pathophysiology of ischemia and reperfusion. With respect to beta-adrenoceptor signal transduction, adaptive changes during ischemia and reperfusion ensure that this critical pathway for the regulation of cardiac function remains intact. Additionally, although the relative contribution of alpha 1-adrenoceptors to the regulation of cardiac function is minimal in normal myocardium, these receptors clearly exacerbate conditions associated with the generation of arrhythmias during reperfusion. It is likely that this enhancement of arrhythmogenesis is related to the activation of NHE by a PKC-dependent mechanisms. The importance of non-receptor-mediated signal transduction as a mediator of ischemia and reperfusion injury has long been established with respect to products of membrane lipid breakdown. As discussed, recent evidence now suggests that other compounds formed during ischemia and reperfusion, such as reactive oxygen species and NO, are also linked to cellular second messenger systems. In conclusion, as signal transduction is critical for normal myocardial function, signal transduction pathways are of even more importance during ischemia and reperfusion. There is an increasing interest in the role of non-receptor-mediated signal transduction as a mediator of ischemia and reperfusion injury and it is hoped that these pathways may represent new levels for therapeutic intervention.
authors.affiliation: Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
authors.forename: C A
authors.initials: CA
authors.lastname: Ward
authors.forename: M P
authors.initials: MP
authors.lastname: Moffat
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D004075:Diglycerides; D010743:Phospholipids; D017382:Reactive Oxygen Species; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D000242:Cyclic AMP; D011493:Protein Kinase C; D019204:GTP-Binding Proteins