Current pharmaceutical design
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Review
Anesthetic cardioprotection in clinical practice from proof-of-concept to clinical applications.
In 2007, the American Heart Association (AHA) recommended (class IIa, level of evidence B) in their guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery volatile anesthetics as first choice for general anesthesia in hemodynamically stable patients at risk for myocardial ischemia. This recommendation was based on results from patients undergoing coronary artery bypass grafting (CABG) surgery and thus subject to criticism. However, since a "good anesthetic" often resembles a piece of art in the complex perioperative environment, and is difficult to highly standardize, it seems unlikely that large-scale randomized control trials in noncardiac surgical patients will be performed in the near future to tackle this question. ⋯ In patients at risk for perioperative cardiovascular complications, it is essential to abandon the use of "anti-conditioning" drugs (sulfonylureas and COX-2 inhibitors) and probably glitazones. There is significant interference in cardioprotection between sevoflurane and propofol, which should not be used concomitantly during anesthesia if possible. Any type of ischemic "conditioning" appears to exhibit markedly reduced protection or completely loses protection in the presence of volatile anesthetics and/or opioids.
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Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. ⋯ Among the promising strategies to ameliorate mitochondrial-based diseases these authors highlight the induction of PGC-1α via activation of PPAR receptors (rosiglitazone, bezafibrate) or modulating its activity by AMPK (AICAR, metformin, resveratrol) or SIRT1 (SRT1720 and several isoflavone-derived compounds). This article also presents a review of the current animal and cellular models useful to study mitochondriogenesis. Although it is known that many neurodegenerative and neurodevelopmental diseases are originated in mitochondria, the regulation of mitochondrial biogenesis has never been extensively studied. (ABSTRACT TRUNCATED)
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Caveolae are flask-like invaginations of the cell surface that have been identified as signaling epicenters. Within these microdomains, caveolins are structural proteins of caveolae, which are able to interact with numerous signaling molecules affecting temporal and spatial dimensions required in cardiac protection. ⋯ In this review we will outline a general overview of caveolae and caveolins and their role in protective signaling with a focus on the effects of volatile anesthetics. These recent developments have allowed us to better understand the mechanistic effect of volatile anesthetics and their potential in cardiac protection.
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Post cardiac surgery acute kidney injury (AKI) is common, poorly understood and associated with a significant increase in morbidity and mortality. ⋯ There is a paucity of effective renoprotective agents that can be used in adult cardiac surgical patients. There is an urgent need to develop novel renoprotective strategies.