Cellular Signal Transduction Pathways for Anesthetic-induced Cardioprotection

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Citation
US Cardiology, 2006;3(1):1-5

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Cardiovascular disease is a major healthcare problem in the US. The presence of this disease significantly affects the outcome of both cardiac and non-cardiac surgery, and peri-operative cardiac morbidity is one of the leading causes of death following anesthesia and surgery. The considerable incidence of myocardial infarction, congestive heart failure, myocardial ischemia, or serious dysrhythmias during the intra-operative or post-operative periods has led many studies to examine medical factors and interventions for decreasing cardiac risk in patients with cardiovascular disease. An extensive amount of work has focused on whether any one anesthetic agent or technique is particularly beneficial for patients with coronary artery disease (CAD). Experimental studies conducted in the laboratory have clearly demonstrated that volatile anesthetics exert profound cardioprotection against myocardial ischemia and reperfusion injury. The purpose of this overview is to summarize the interaction of volatile anesthetics with ischemic myocardium and briefly discuss the underlying mechanisms of cardioprotection against ischemia and reperfusion injury.

Discussion

Myocardium is sensitive to hypoxia and ischemia, which can lead to extensive and irreversible tissue injury. However, short periods of ischemia, called ischemic pre-conditioning (IPC), prior to a prolonged ischemic insult, can reduce the severity of cardiac injury. IPC has been studied extensively for the past 20 years and has resulted in the publication of more than 2,000 articles, which have significantly increased our understanding of the cellular mechanisms of ischemia and reperfusion injury. IPC was initially described in 19861 by Murray et al., who demonstrated that four five-minute periods of coronary artery occlusion interspersed with five-minute periods of reperfusion before a prolonged coronary occlusion produced a reduction in myocardial infarct size in dogs. Pre-conditioning can also be induced in humans undergoing percutaneous transluminal coronary angioplasty with a coronary occlusion of two minutesÔÇÖ duration.2

Certain pharmacological agents can mimic IPC. Experimental and clinical data indicate that volatile anesthetics may pre-condition the myocardium against ischemia and infarction by activating endogenous protective cellular mechanisms. This is anesthetic-induced pre-conditioning (APC).3 Myocardial protection by volatile anesthetics is of clinical relevance for patients with CAD because of their high morbidity and because of their mortality, which is secondary to peri-operative myocardial ischemia. The beneficial effects of APC in patients have also been reported.4-10

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