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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary artery disease (CAD) is very prevalent in Western societies and is a leading cause of mortality and morbidity. Despite decreases in mortality rates from CAD over the past 30 years, ischemic heart failure remains an important problem because people with CAD are now living longer. Hibernating myocardium may be defined as reversible left ventricular dysfunction due to chronic CAD that shows improvement in function after revascularization. Many patients with ischemic cardiomyopathy have areas of hibernating myocardium, and thus can potentially show improvement in left ventricular regional and global function if they are revascularized. Whether hibernating myocardium represents an adaptive response to hypoperfusion in the face of chronic ischemia or whether it is a degenerative process is not entirely clear. Clearly, ultrastructural changes of de-differentiation are seen, and include loss of sarcomeres and the appearance of small mitochondria and glycogen accumulation. Although the mechanisms underlying the changes in morphology and depressed contractility, and the factors governing recovery of function are not clear, changes in adrenergic receptor density, cytokine upregulation, and the degree of fibrosis may all play a role. Identification of viability is commonly performed with dobutamine echocardiography or nuclear imaging. Because patients with extensive CAD and poor left ventricular systolic function are high-risk candidates for coronary bypass surgery, the preoperative identification of viability provides important prognostic information. Patients with viable myocardium who are treated with revascularization rather than medical therapy have better outcomes in terms of survival, left ventricular function, symptoms, and exercise capacity.
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PMID:Myocardial hibernation in coronary artery disease. 1182 79

Heme oxygenase (HO)-1 converts heme to bilirubin, carbon monoxide, and iron. Our prior work has suggested a cardioprotective role for HO-1 in heart failure. To test whether HO-1 (heat shock protein 32) prevents cardiomyocyte apoptosis and cardiac dysfunction after ischemia-reperfusion (I/R), we generated transgenic mice overexpressing HO-1 in the heart under the control of the alpha-myosin heavy chain promoter. HO-1 transcript and protein increased markedly in the heart only. In an isolated heart preparation, we observed an enhanced functional recovery during reperfusion after ischemia in the transgenic hearts compared with nontransgenic controls. I/R injury was also performed in intact animals by coronary ligation and reperfusion to assess the protective role of HO-1 overexpression on heart apoptosis. HO-1 overexpression reduced cardiac apoptosis, as evidenced by fewer terminal deoxynucleodidyl transferase-mediated dUTP nick-end labeling-positive or in situ oligo ligation-positive myocytes, compared with nontransgenic mice. Our results indicate that cardioselective overexpression of HO-1 exerts a cardioprotective effect after myocardial I/R in mice, and this effect is probably mediated via an antiapoptotic action of HO-1.
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PMID:Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis. 1212 17

A considerable number of experimental, epidemiological and clinical studies are now available which point to an important role of Mg2+ in the etiology of cardiovascular pathology. In human subjects, hypomagnesemia is often associated with an imbalance of electrolytes such as Na+, K+ and Ca2+. Abnormal dietary deficiency of Mg2+ as well as abnormalities in Mg2+ metabolism play important roles in different types of heart diseases such as ischemic heart disease, congestive heart failure, sudden cardiac death, atheroscelerosis, a number of cardiac arrhythmias and ventricular complications in diabetes mellitus. Mg2+ deficiency results in progressive vasoconstriction of the coronary vessels leading to a marked reduction in oxygen and nutrient delivery to the cardiac myocytes. Numerous experimental and clinical data have suggested that Mg2+ deficiency can induce elevation of intracellular Ca2+ concentrations, formation of oxygen radicals, proinflammatory agents and growth factors and changes in membrane perrmeability and transport processes in cardiac cells. The opposing effects of Mg2+ and Ca2+ on myocardial contractility may be due to the competition between Mg2+ and Ca2+ for the same binding sites on key myocardial contractile proteins such as troponin C, myosin and actin. Stimulants, for example, catecholamines can evoke marked Mg2+ efflux which appears to be associated with a concomitant increase in the force of contraction of the heart. It has been suggested that Mg2+ efflux may be linked to the Ca2+ signalling pathway. Depletion of Mg2+ by alcohol in cardiac cells causes an increase in intracellular Ca2+, leading to coronary artery vasospasm, arrhythmias, ischemic damage and cardiac failure. Hypomagnesemia is commonly associated with hypokalemia and occurs in patients with hypertension or myocardial infarction as well as in chronic alcoholism. The inability of the senescent myocardium to respond to ischemic stress could be due to several reasons. Mg2+ supplemented K+ cardioplegia modulates Ca2+ accumulation and is directly involved in the mechanisms leading to enhanced post ischemic functional recovery in the aged myocardium following ischemia. While many of these mechanisms remain controversial and in some cases speculative, the beneficial effects related to consequences of Mg2+ supplementation are apparent. Further research are needed for the incorporation of these findings toward the development of novel myocardial protective role of Mg2+ to reduce morbidity and mortality of patients suffering from a variety of cardiac diseases.
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PMID:Protective role of magnesium in cardiovascular diseases: a review. 1234 4

In patients with chronic heart failure, myocardial contractile responsiveness to dobutamine is diminished as a result of beta-receptor desensitization due to chronic adrenergic activation. Changes in beta-receptor effector mechanisms are more marked in idiopathic dilated cardiomyopathy (IDCM) than in ischemic dilated cardiomyopathy. As the magnitude of the dobutamine effect is proportional to the severity of left ventricular systolic dysfunction, the heterogeneous cardiotonic effects of dobutamine in IDCM may represent different evolutive stages of a progressive disease process. On the basis of this pathophysiologic background, some studies were undertaken to investigate the prognostic and functional implications of dobutamine stress echocardiography (DSE) in IDCM. Prognostic studies consistently suggest that myocardial response to dobutamine is related to the clinical outcome. However, the limited number of patients and events in the individual studies are important limitations. Moreover, the impact of beta-blockers on the potential ability of DSE to predict the prognosis needs to be assessed. A few studies also suggest that changes in left ventricular systolic function parameters following dobutamine infusion are related to exercise tolerance, as assessed by peak exercise oxygen consumption and functional recovery of the failing myocardium. The data suggest that DSE is a promising method, which may improve the risk stratification process in patients with IDCM and provide further insights into the pathophysiologic mechanisms underlying progressive systolic pump dysfunction and exercise intolerance. Further studies are however needed to define the role of DSE in IDCM.
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PMID:The role of dobutamine stress echocardiography in idiopathic dilated cardiomyopathy. 1511 11

Despite dramatic advances in the treatment of acute myocardial infarction (AMI) in recent years, patients with diabetes mellitus continue to experience disproportionately high morbidity and mortality. A substantial body of experimental and clinical data suggest that the ability of the heart to augment its energetic metabolism of glucose in the acute setting is critical to survival and functional recovery after AMI. Emerging evidence also suggests that chronic hyperglycemia may predispose to post-AMI ischemia and heart failure via adverse effects on coronary endothelial function and myocardial ultrastructure, energy metabolism, and gene transcription. A strong case can be made for intensive insulin-based control of glycemic level in the AMI patient with diabetes mellitus.
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PMID:Glucose and insulin management in the post-MI setting. 1264 21

The renin-angiotensin system is activated during myocardial ischemia, and angiotensin II is locally formed in ischemic hearts. At least four angiotensin II receptor subtypes have been identified, the AT1- and the AT2-receptor being the most prominent in the cardiovascular system. AT1-receptor blockade--like inhibition of the angiotensin-converting-enzyme (ACE)--limits infarct size, improves functional recovery following myocardial ischemia and attenuates ventricular remodeling, post-myocardial infarction and the resulting development of heart failure. The potential mechanisms responsible for the cardioprotection by AT1-receptor blockade remain to be elucidated in detail, but appear to involve AT2-receptor activation and--like ACE-inhibitors--bradykinin and prostaglandins. Combined treatment with ACE-inhibitors and AT1-receptor blockers has the potential to further reduce infarct size and improve ventricular remodeling over each monotherapy alone.
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PMID:AT1-receptor blockade in experimental myocardial ischemia/reperfusion. 1294 May 36

Coronary artery disease and its sequelae-ischemia, myocardial infarction, and heart failure-are leading causes of morbidity and mortality in man. Considerable effort has been devoted toward improving functional recovery and reducing the extent of infarction after ischemic episodes. As a step in this direction, it was found that the heart was significantly protected against ischemia-reperfusion injury if it was first preconditioned by brief ischemia or by administering a potassium channel opener. Both of these preconditioning strategies were found to require opening of a K(ATP) channel, and in 1997 we showed that this pivotal role was mediated by the mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)). This paper will review the evidence showing that opening mitoK(ATP) is cardioprotective against ischemia-reperfusion injury and, moreover, that mitoK(ATP) plays this role during all three phases of the natural history of ischemia-reperfusion injury preconditioning, ischemia, and reperfusion. We discuss two distinct mechanisms by which mitoK(ATP) opening protects the heart-increased mitochondrial production of reactive oxygen species (ROS) during the preconditioning phase and regulation of intermembrane space (IMS) volume during the ischemic and reperfusion phases. It is likely that cardioprotection by ischemic preconditioning (IPC) and K(ATP) channel openers (KCOs) arises from utilization of normal physiological processes. Accordingly, we summarize the results of new studies that focus on the role of mitoK(ATP) in normal cardiomyocyte physiology. Here, we observe the same two mechanisms at work. In low-energy states, mitoK(ATP) opening triggers increased mitochondrial ROS production, thereby amplifying a cell signaling pathway leading to gene transcription and cell growth. In high-energy states, mitoK(ATP) opening prevents the matrix contraction that would otherwise occur during high rates of electron transport. MitoK(ATP)-mediated volume regulation, in turn, prevents disruption of the structure-function of the IMS and facilitates efficient energy transfers between mitochondria and myofibrillar ATPases.
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PMID:Mitochondrial potassium transport: the role of the mitochondrial ATP-sensitive K(+) channel in cardiac function and cardioprotection. 1450 24

In patients with acute myocardial infarction (AMI) primary angioplasty and stent placement is a more effective and better tolerated treatment than thrombolysis, and therefore, when logistics allow, this treatment is preferred and routinely used. However, successful reopening of an occluded coronary artery does not necessarily lead to recovery of left ventricular (LV) function. Post-AMI reduction in contractile function and ventricular remodeling may result in heart failure. There is evidence that reduced contractile function in the infarct zone is related to poor microvascular perfusion even after normalization of large-vessel flow by angiographic criteria following coronary recanalization. Failure to re-establish adequate tissue perfusion may be because of reperfusion injury, ischemia-induced microvascular damage, and plugging of the microcirculation by thrombus and plaque during mechanical recanalization. Experimental data support the hypothesis that reperfusion microvascular ischemia contributes to myocardial tissue injury over a prolonged time period. Hyperbaric oxygen therapy (HBO) attenuates microvascular dysfunction and reperfusion microvascular ischemia, as demonstrated in both experimental models and patients with AMI. However, treating patients in an HBO chamber or with a conventional oxygenator is impractical and difficult. Aqueous oxygen (AO) is a newly developed solution containing extremely high oxygen concentrations (1-3 ml O(2)/mL saline). The AO system mixes AO solution with a patient's blood from an arterial puncture and delivers the hyperoxemic blood to targeted ischemic myocardium via an infusion catheter for regional correction of hypoxemia and production of hyperoxemia. The system precisely controls the level of pO(2) without clinically significant microbubble formation. Hyperoxemic coronary infusion of AO in experimental models of AMI improved LV function and reduced infarct size compared with normoxemic controls,very likely as a result of microvascular blood flow improvement. The first clinical experiences with intracoronary infusion of AO solution demonstrated the therapy to be a safe and well tolerated in the setting of AMI after successful primary percutaneous transluminal coronary angioplasty. Its use was associated with significant progressive improvement in LV function as measured by ejection fraction and wall motion score index. Interestingly, such improvement was primarily due to functional recovery of infarct zone contractility. A larger randomized trial is currently underway to define the role of hyperoxemic coronary infusion in patients with AMI.
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PMID:Hyperoxemic perfusion for treatment of reperfusion microvascular ischemia in patients with myocardial infarction. 1472 78

Cytosolic Ca(2+) overload is a critical mediator of myocardial damage following cardiac ischemia-reperfusion. It has therefore been proposed that normalization of sarcoplasmic reticulum Ca(2+) cycling through inhibition or ablation of the Ca(2+) ATP-ase inhibitor phospholamban (PLN), which shows promise as a treatment for heart failure, could be beneficial in ischemic heart disease. However, a recent study has shown that globally ischemic PLN-deficient hearts exhibit increased ischemic injury, with impaired contractile, ATP, and phosphocreatine recoveries, compared to wild-type hearts. Since protein kinase C (PKC) family members are widely recognized as mediators of both post-ischemic injury and ischemic preconditioning, we assessed PKC levels in PLN-deficient hearts. Compared to genetically normal hearts, PLN-deficient hearts exhibited diminished particulate partitioning of PKC, a known cardioprotective PKC isoform, without alterations in the levels of membrane-associated PKC delta nor PKC alpha. To determine if decreased particulate partitioning of cardioprotective PKC epsilon was a cause of increased ischemic injury in PLN-deficient hearts, PLN-deficient mice were mated with mice expressing a myocardial-specific PKC epsilon translocation activator peptide, pseudo-epsilon receptor for activated kinase C (psi epsilon RACK). In psi epsilon RACK/PLN knockout (KO) hearts, PKC epsilon translocation to membranous cellular structures was augmented and this was associated with a significant acceleration of post-ischemic contraction and relaxation rates, as well as reduction of creatine phosphokinase release, compared to PLN-deficient hearts. Importantly, post-ischemic functional recovery reached pre-ischemic hyperdynamic values in psi epsilon RACK/PLN KO hearts, indicating super-rescue by the combination of PLN ablation and psi epsilon RACK expression. These findings suggest that diminished PKC epsilon particulate partitioning in PLN-deficient hearts is associated with attenuated contractile recovery upon ischemia-reperfusion and that increased translocation of PKC to membranous cellular structures confers full cardioprotection.
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PMID:Increased particulate partitioning of PKC epsilon reverses susceptibility of phospholamban knockout hearts to ischemic injury. 1487 59

This article first discusses coronary artery disease, including left-ventricular dysfunction, hibernating myocardium, the relationship between stunning, hibernation, and heart failure, and molecular mechanisms underlying myocardial hibernation. Left ventricular function and the prognosis and pathophysiology of left-ventricular dysfunction are then examined. Selection of patients for revascularization is discussed, to include which coronary patients should be investigated for myocardial viability, and other surgical considerations are outlined. The outcome following revascularization in the heart failure patient, the results of revascularization, and the time course of functional recovery after coronary artery bypass graft are also covered.
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PMID:Coronary revascularization in ischemic cardiomyopathy. 1505 89


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