Journal of cardiovascular pharmacology and therapeutics
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J. Cardiovasc. Pharmacol. Ther. · Sep 2011
Development of an NIH consortium for preclinicAl AssESsment of CARdioprotective therapies (CAESAR): a paradigm shift in studies of infarct size limitation.
An estimated 935,000 Americans suffer a myocardial infarction every year; because their prognosis is determined by the size of the infarct, reducing infarct size is of paramount importance to alleviate morbidity and mortality. For 40 years, the National Heart, Lung, and Blood Institute (NHLBI) has invested enormous resources (at least several hundred million dollars) in preclinical studies aimed at developing infarct-sparing therapies, and several hundred (if not thousands) therapies have been claimed to limit infarct size in preclinical models. Unfortunately, due largely to methodological problems, this enormous investment has not produced any notable clinical application, and no cardioprotective therapy is currently available for clinical use. ⋯ Consortium for preclinicAl assESsment of cARdioprotective therapies will be a major paradigm shift in cardioprotection. By screening promising therapies and identifying those that are truly effective in relevant experimental models and, thus, most likely to be effective in patients, CAESAR will dramatically advance our ability to rationally translate basic findings into clinical use. This article will summarize the rationale, structure, and operation of the NHLBI CAESAR Consortium.
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J. Cardiovasc. Pharmacol. Ther. · Sep 2011
ReviewRemote ischemic preconditioning: current knowledge, unresolved questions, and future priorities.
Remote ischemic preconditioning (RIPC) is the phenomenon whereby brief episodes of ischemia-reperfusion applied in distant tissues or organs render the myocardium resistant to a subsequent sustained episode of ischemia. Reduction of infarct size with RIPC has been documented in response to (i) brief antecedent ischemia in a remote coronary vascular bed (intra-cardiac protection); (ii) collection and transfer of coronary effluent from perconditioning "donor" hearts to naive "receptor" hearts (inter-cardiac protection); (iii) brief ischemia applied in skeletal muscle, mesentery, and other organs (interorgan protection); and (iv) remote nociception ("remote PC of trauma"). ⋯ Progress has also been made in translating the concept of RIPC to patients undergoing planned ischemic events: evidence for attenuation of cardiac enzyme release with RIPC has been reported after elective abdominal aortic aneurysm repair, angioplasty, and coronary artery bypass graft surgery. However, despite these advances in characterization and clinical application, the mechanisms of RIPC--most notably, the means by which the protective stimulus is communicated to the heart--remain poorly defined and, in all likelihood, are model dependent.