domingo, 12 de junio de 2016

Cardioprotección / Cardiac protection

Junio 8, 2016. No. 2351

Postcondicionamiento isquémico: la protección cardiaca después del evento.
Ischaemic postconditioning: cardiac protection after the event.
Anaesthesia. 2015 May;70(5):598-612. doi: 10.1111/anae.12974. Epub 2015 Feb 16.
Ischaemic heart disease remains the leading cause of death worldwide. Novel approaches to improve morbidity and mortality in this population are essential. Cardiac ischaemic postconditioning - the technique of applying alternating cycles of sublethal myocardial ischaemia and reperfusion after a sustained insult - is one cardioprotective strategy that can reduce reperfusion injury. Infarct size reduction and improvements in left ventricular ejection fraction have been demonstrated with mechanical or pharmacological postconditioning, both after spontaneous acutemyocardial infarction, and associated with cardiac surgery. Nonetheless, the benefits of postconditioning can be easily attenuated. For maximal benefit, postconditioning demands a particular patient population (large area at risk, with little collateral blood flow), timely application and the measurement of appropriate clinical endpoints. Furthermore, confounders such age, sex and medication, as well as a plethora of co-morbidities common in patients with ischaemic heart disease, all impact on the efficacy of postconditioning. This fragility requires the security of outcomes from large-scale human trials to ensure robust applicability to everyday clinical practice, and to provide assurance of an impact on long-term clinical outcome. This review highlights the development of current postconditioning algorithms, the findings from current proof-of-concept trials, and the barriers that may limit its broad uptake into clinical practice.
 Cardioprotección por condicionamiento isquémico remoto. Mecanismos y evidencias clínicas
Cardioprotection by remote ischemic conditioning: Mechanisms and clinical evidences.
World J Cardiol. 2015 Oct 26;7(10):621-32. doi: 10.4330/wjc.v7.i10.621.
In remote ischemic conditioning (RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to theischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site (remote ischemic preconditioning), during the ischemic insult (remote ischemic perconditioning) or at the onset of reperfusion (remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy.
KEYWORDS: Atherosclerosis; Cardiac surgery; Ischemic heart disease; Percutaneous coronary intervention; Remote ischemic conditioning
Condicionamiento isquémico: Tropiezos en el camino hacia el uso clínico
Ischaemic conditioning: pitfalls on the path to clinical translation.
Br J Pharmacol. 2015 Apr;172(8):1961-73. doi: 10.1111/bph.13064. Epub 2015 Feb 27.
The development of novel adjuvant strategies capable of attenuating myocardial ischaemia-reperfusion injury and reducing infarct size remains a major, unmet clinical need. A wealth of preclinical evidence has established that ischaemic 'conditioning' is profoundly cardioprotective, and has positioned the phenomenon (in particular, the paradigms of postconditioning and remote conditioning) as the most promising and potent candidate for clinical translation identified to date. However, despite this preclinical consensus, current phase II trials have been plagued by heterogeneity, and the outcomes of recent meta-analyses have largely failed to confirm significant benefit. As a result, the path to clinical application has been perceived as 'disappointing' and 'frustrating'. The goal of the current review is to discuss the pitfalls that may be stalling the successful clinical translation of ischaemic conditioning, with an emphasis on concerns regarding: (i) appropriate clinical study design and (ii) the choice of the 'right' preclinical models to facilitate clinical translation.

Condicionamiento isquémico: El reto de proteger el corazón diabético
Ischemic conditioning: the challenge of protecting the diabetic heart.
Cardiovasc Diagn Ther. 2014 Oct;4(5):383-96. doi: 10.3978/j.issn.2223-3652.2014.10.05.
The successful clinical translation of novel therapeutic strategies to attenuate lethal myocardial ischemia-reperfusion injury and limit infarct size has been identified as a major unmet need, and is of particular importance in patients with type-2 diabetes. There is a wealth of preclinical evidence that ischemic conditioning (encompassing the three paradigms of preconditioning, postconditioning and remote conditioning) is profoundly cardioprotective and, via up-regulation of endogenous signaling cascades, renders the heart resistant to infarction. However, current phase II trials aimed at exploiting ischemic conditioning for the clinical treatment of myocardial ischemia-reperfusion injury have yielded mixed results, possibly reflecting the emerging concern that the efficacy of conditioning-induced cardioprotection may be compromised in the diabetic heart. Our goal in this review is to provide a summary of our present understanding of the effect of type-2 diabetes on the infarct-sparing effect of ischemic conditioning, and the challenges of limiting ischemia-reperfusion injury in the diabetic heart.
KEYWORDS: Myocardial infarction; diabetes; postconditioning; preconditioning; remote conditioning

VIII Foro Internacional de Medicina del Dolor y Paliativa 
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Junio 9-11, Ciudad de México
Dra. Argelia Lara Solares
Tel. 5513 3782 
Cursos de Anestesiología en Chile, 2016
Facultad de Medicina. Pontificia Universidad Católica de Chile
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