Current drug targets
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Current drug targets · Sep 2009
Reducing the risk of major elective non-cardiac surgery: is there a role for levosimendan in the preoperative optimization of cardiac function?
Patients with heart failure undergoing non-cardiac surgery still have an unacceptably high morbidity and mortality. Compromised myocardial physiologic reserves in combination with extensive surgery and anesthesia appear to play a crucial role in determining high perioperative morbidity and mortality. Nevertheless, several other mechanisms and pathways such as metabolic factors, ischemia-reperfusion conditions, neurohormonal activation, inflammation and oxidative stress contribute to the adverse outcome. ⋯ At the cellular level in the heart, kidney, lung, liver as well as the gut, levosimendan exerts protective preconditioning effects secondary to activation of adenosine triphosphate (ATP)-sensitive potassium channels. Taking into account these multiple but complementary mechanisms, levosimendan appears to be a suitable agent for preoperative optimization of cardiac functions in heart failure patients undergoing major elective surgery. Nevertheless, large-scale trials are needed before final conclusions can be drawn on the use of levosimendan in this indication.
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Critical illness and particularly sepsis are associated with a significant redox imbalance resulting from an increased production of oxidant species and a decrease in endogenous antioxidant defences. In critical patients sources of oxidative stress include the mitochondrial respiratory electron transport chain, xanthine oxidase activation, the respiratory burst associated with neutrophil activation, and arachidonic acid metabolism. Several endogenous antioxidants have been identified including enzymes, like superoxide dismutases and glutathione peroxidase, vitamins and other molecules such as uric acid and bilirubin. ⋯ Melatonin is a promising molecule that deserves the attention of future research, as well as vitamin C. Further studied should also try to establish the more beneficial combination of antioxidants, as well as the doses, and the timing of administration. When such problems will be resolved hopefully results about antioxidant therapy in critical illness will be more univocal and promising.
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Current drug targets · Sep 2009
ReviewBeta-Blockers in the perioperative period: are there indications other than prevention of cardiac ischemia?
Beta-blocker therapy is accepted to reduce perioperative cardiovascular complications. Moreover, beta-blockers have potentially beneficial effects other than prevention of cardiac events. ⋯ Beta-blockers are also useful in stabilizing hemodynamics during electroconvulsive therapy, intubation and emergency periods. Physicians need to bear in mind the benefits of beta-blockers for purposes other than preventing cardiac events when applied in the perioperative period, and should be familiar with the pharmacodynamics and effective dosages of these agents.