Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process
ABSTRACT Myocardial infarction is the major cause of death in the world. Over the last two decades, coronary reperfusion therapy has become established for the management of acute myocardial infarction (AMI). However, restoration of blood flow to previously ischemic myocardium results in the so-called ischemia/reperfusion (IR)-injury. The different clinical manifestations of this injury include myocardial necrosis, arrhythmia, myocardial stunning and endothelial- and microvascular dysfunction including the no-reflow phenomenon. The pathogenesis of ischemia/reperfusion injury consists of many mechanisms. Recently, there's increasing evidence for an important role in IR-injury on hypercontracture induced by high levels of cytosolic calcium or by low concentrations of ATP. In the last years, many studies on experimental models were investigated, but the clinical trials confirming these effects remain spare. Recently, the beneficial effect of Na(+)/H(+)-exchange inhibitor cariporide and of the oxygen-derived free radical (ODFR) scavenger vitamin E on coronary bypass surgery-induced IR-injury were demonstrated. Also recently, the beneficial effect of allopurinol on the recovery of left ventricular function after rescue balloon-dilatation was demonstrated. The beneficial effect of magnesium and trimetazidine on IR-injury remains controversial. The beneficial effect of adenosine remains to be further confirmed. There's also increasing interest in agentia combining the property of upregulating NO-synthase (e.g. L-arginine) and restoring the balance between NO and free radicals (e.g. tetrahydrobiopterin). One of such agents could be folic acid. In this review article the authors give an overview of the recent insights concerning pathogenesis and therapeutic possibilities to prevent IR-induced injury.
SourceAvailable from: Tiziano M Scarabelli[Show abstract] [Hide abstract]
ABSTRACT: A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cytoplasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion (I/R) injury. This tightly orchestrated catabolic cellular 'housekeeping' process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protective mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the variability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin (mTOR) inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic manipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.
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ABSTRACT: Ischemic heart disease is one of the major causes of death worldwide. Ischemia is a condition in which blood flow of the myocardium declines, leading to cardiomyocyte death. However, reperfusion of ischemic regions decreases the rate of mortality, but it can also cause later complications. In a clinical setting, ischemic heart disease is always coincident with other co-morbidities such as diabetes. The risk of heart disease increases 2-3 times in diabetic patients. Apoptosis is considered to be one of the main pathophysiological mechanisms of myocardial ischemia-reperfusion injury. Diabetes can disrupt the anti-apoptotic intracellular signaling cascades involved in myocardial protection. Therefore, targeting these changes may be an effective cardioprotective approach in the diabetic myocardium against ischemia-reperfusion injury. In this article, we review the interaction of diabetes with the pathophysiology of myocardial ischemia-reperfusion injury, focusing on the contribution of apoptosis in this context, and then discuss the alterations of pro-apoptotic or anti-apoptotic pathways probably responsible for the loss of cardioprotection in diabetes.
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ABSTRACT: Carotenoids are a class of natural, fat-soluble pigments found principally in plants. They have potential antioxidant biological properties because of their chemical structure and interaction with biological membranes. Epidemiologic studies supported the hypothesis that antioxidants could be used as an inexpensive means of both primary and secondary cardiovascular disease (CVD) prevention. In fact, the oxidation of low-density lipoproteins (LDL) in the vessels plays a key role in the development of atherosclerotic lesions. The resistance of LDL to oxidation is increased by high dietary antioxidant intake, so that carotenoids, as part of food patterns such as the Mediterranean diet, may have beneficial effects on cardiovascular health too. Further properties of carotenoids leading to a potential reduction of cardiovascular risk are represented by lowering of blood pressure, reduction of pro-inflammatory cytokines and markers of inflammation (such as C-reactive protein), and improvement of insulin sensitivity in muscle, liver, and adipose tissues. In addition, recent nutrigenomics studies have focused on the exceptional ability of carotenoids in modulating the expression of specific genes involved in cell metabolism. The aim of this review is to focus attention to this effect of some carotenoids to prevent CVD.Food & Nutrition Research 02/2015; 59:26762. DOI:10.3402/fnr.v59.26762 · 1.79 Impact Factor