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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial hibernation refers to a state of persistent regional ventricular dysfunction, in patients with coronary artery disease that is reversible with revascularization. It is part of the spectrum of pathophysiological responses to myocardial ischemia and is a particularly important concept in understanding the development and progression of ischemic cardiomyopathy. Hibernating myocardium may be associated with chronic hypoperfusion, or result from repetitive episodes of ischemia with a cumulative effect on contractile function. Mechanistic studies on myocardial hibernation have been hampered by the difficulty in developing a reproducible and reliable animal model. This review describes the pathologic changes found in hibernating myocardial segments discussing the potential mechanisms involved in their development. Depletion of cardiomyocyte contractile elements, loss of myofilaments and disorganization of cytoskeletal proteins are among the most consistently reported morphological alterations found in hibernating myocardial segments. In addition, the cardiac intersitium exhibits inflammatory changes, leading to fibrotic remodeling. Induction of cytokines and chemokines suggests an active continuous inflammatory process leading to fibrosis and dysfunction. Although, the initial response may be adaptive to ischemia, if timely revascularization is not performed, irreversible tissue injury, fibrosis and myocyte degeneration may develop. Understanding the role of inflammatory mediators in the development and progression of the cardiomyopathic process may lead to the development of specific therapeutic strategies aiming at preventing irreversible fibrosis and dysfunction.
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PMID:The pathological basis of myocardial hibernation. 1264 14

This study was designed to evaluate several electromechanical mapping parameters for assessment of myocardial viability and inducible ischemia as defined by dipyridamole single-photon emission computed tomographic (SPECT) imaging at rest in patients with severe ischemic cardiomyopathy. Unipolar voltage, normalized unipolar voltage, bipolar voltage, and fragmentation were compared with tracer uptake at rest and reversibility on stress or rest quantitative technetium-99m sestamibi SPECT imaging in 32 patients with severe ischemic cardiomyopathy (left ventricular ejection fraction 0.24 +/- 0.08). In dysfunctional myocardial segments, logistic regression showed unipolar voltage, normalized unipolar voltage, and bipolar voltage to be predictive of viable myocardium (> or = 60% tracer uptake at rest) and was significantly higher in viable than in nonviable segments (p <0.01). A unipolar voltage of > or = 7.1 mV was the best predictor of viable myocardium. In dysfunctional viable segments, unipolar voltage was significantly higher in reversible than in fixed segments (p <0.001), and a unipolar voltage of > or = 8.5 mV had optimal power for identifying reversibility on dipyridamole SPECT imaging. We conclude that in patients with severe ischemic cardiomyopathy, unipolar voltage can identify viable from nonviable myocardium and reversible from fixed viable defects as defined by dipyridamole technetium-99m sestamibi SPECT imaging.
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PMID:Electromechanical mapping for detecting myocardial viability and ischemia in patients with severe ischemic cardiomyopathy. 1266 65

Myocardial function depends on adenosine triphosphate (ATP) supplied by oxidation of several substrates. In the adult heart, this energy is obtained primarily from fatty acid oxidation through oxidative phosphorylation. However, the energy source may change depending on several factors such as substrate availability, energy demands, oxygen supply, and metabolic condition of the individual. Surprisingly, the role of energy metabolism in development of cardiac diseases has not been extensively studied. For instance, alterations in glucose oxidation and transport developed in diabetic heart may compromise myocardial performance under conditions in which ATP provided by glycolysis is relevant, such as in ischemia and reperfusion. In some cardiac diseases such as ischemic cardiomyopathy, heart failure, hypertrophy, and dilated cardiomyopathy, ATP generation is diminished by derangement of fatty acid delivery to mitochondria and by alteration of certain key enzymes of energy metabolism. Shortage of some co-factors such as L-carnitine and creatine also leads to energy depletion. Creatine kinase system and other mitochondrial enzymes are also affected. Initial attempts to modulate cardiac energy metabolism by use of drugs or supplements as a therapeutic approach to heart disease are described.
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PMID:Heart metabolic disturbances in cardiovascular diseases. 1270 3

Pyruvate is an energy substrate with known cardioprotective activity. We know now that this is due not only to its antioxidant activity, but also to its reduction of intracellular acidosis, modulation of intracytosolic calcium and improvement of cardiomyocyte contractility. However, the role of cardiac mitochondria in such positive effects has only recently begun to be understood and the exact mechanisms of the effect of pyruvate on mitochondria are still largely unknown. Aiming to study the effect of pyruvate on cardiac mitochondrial function during acute ischemia, we used an ex-vivo animal model, perfused in a Langendorff system and then subjected to ischemia in the presence and absence of pyruvate. We evaluated the mitochondrial membrane electrical potential, the respiratory chain O2 consumption (and respiratory control ratio) and the energy charges generated with different energy substrates. We conclude that pyruvate has some effect on the mitochondrial oxidative system (by non-significantly improving the respiratory control ratio), but its main action is on the phosphorylation system, significantly decreasing the time taken to complete a phosphorylation cycle (lag phase) and improving ATP production (increase in energy charge), thus allowing better maintenance of mitochondrial membrane structure, with consequent improvement of the electrical potential after a phosphorylation cycle. These findings have enabled better understanding of the mechanisms behind pyruvate cytoprotection in ischemic cardiomyopathy, clearly highlighting the essential role of cardiac mitochondria in this process.
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PMID:Pyruvate improves mitochondrial bioenergetics in an ex-vivo animal model of myocardial ischemia. 1271 12

Recent advances in the knowledge of the biochemical basis of myocardial ischemia have enabled a better understanding of the complex sequence of events occurring in ischemic cardiomyopathy, whatever its manifestations. This has clearly highlighted the important role played by cardiac mitochondria in these events. At first only associated with energy production, mitochondria have been clearly shown to have other important functions, like the maintenance of calcium homeostasis, as well as ischemic and non-ischemic preconditioning, and also modulation of cellular life and death. The aims of this review are twofold: firstly, to review the current knowledge on mitochondrial morphology and structure, and how these can be affected by ischemia and ischemia-reperfusion; and secondly, to summarize the role of cardiac mitochondria in cardioprotection and modulation of cell death mechanisms.
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PMID:Mitochondria: role in ischemia, reperfusion and cell death. 1276 3

Myocardial hibernation refers to a state of persistent regional contractile ventricular dysfunction, in patients with coronary artery disease that is reversible with revascularization. Identification of hibernating myocardial segments is critical for selecting patients who are most likely to benefit from revascularization procedures. Positron emission tomography, thallium scintigraphy, dobutamine stress echocardiography, myocardial contrast echocardiography and magnetic resonance imaging have been extensively used for detection of viable dysfunctional myocardial segments. Although chronic hypoperfusion and repetitive episodes of brief ischemia may play a role in mediating the changes associated with myocardial hibernation the exact pathogenetic mechanisms are not well understood. The structural alterations found in hibernating myocardial segments involve both the cardio-myocytes and the cardiac interstitium. Depletion of contractile elements, loss of myofilaments, disorganization of myocyte cytoskeletal proteins and alterations in adrenergic receptor density have been reported in segments with reversible systolic dysfunction and may cause segmental hypocontractility. In addition, activation of the inflammatory cascade is noted, leading to cytokine and chemokine induction, leukocyte recruitment, interstitial remodeling and fibrosis. Myocardial hibernation represents a part of the spectrum of ischemic cardiomyopathy, which in the absence of a completed myocardial infarction is a dynamic continuous process ultimately leading to irreversible injury and dysfunction. Understanding of the specific molecular signals involved in the pathogenesis of myocardial hibernation is crucial in order to design strategies preventing irreversible dysfunction.
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PMID:Myocardial hibernation. Clinical and pathological perspectives. 1286 78

Chronic myocardial ischemia is the leading cause of impaired myocardial contractility and heart failure. To identify differentially expressed genes in human ischemic cardiomyopathy (ICM), we constructed a subtracted cDNA library using specimens of ICM compared to normal human heart. Among 100 randomly sequenced clones, seven sequences represented recently identified candidate genes for differential expression in cardiac hypertrophy. A further clone without a known hypertrophy-association coded for the adhesion molecule NCAM(CD56). RNase protection assay, immunohistochemistry, and Western blotting revealed strong overexpression of NCAM(CD56) in all hearts with ICM (n = 14) compared to normal hearts (n = 8), whereas in congestive cardiomyopathy (CCM) (n = 8), hypertrophic obstructive cardiomyopathy (n = 2), myocarditis (n = 4), and sarcoidosis (n = 2), at most slight overexpression of NCAM(CD56) was observed. NCAM(CD56) overexpression abnormally involved the whole cell membrane and the cytoplasma of cardiomyocytes only inside and adjacent to ischemia-induced cardiac scars. Normal or hypertrophic fibers at a distance from ischemic scars were devoid of NCAM overexpression. Identical alterations were observed in an experimental rat ICM model, but not in normal nor in spontaneously hypertensive rat hearts. In search of NCAM(CD56)-related transcription factors we found RUNX1(AML1) up-regulation in ICM and detected RUNX1(AML1) binding within the NCAM(CD56) promoter by electromobility shift assay. We concluded that strong overexpression of NCAM(CD56) and RUNX1(AML1) is a constant and characteristic feature of cardiomyocytes within or adjacent to scars in ICM.
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PMID:NCAM(CD56) and RUNX1(AML1) are up-regulated in human ischemic cardiomyopathy and a rat model of chronic cardiac ischemia. 1293 48

A considerable number of patients with reduced systolic function caused by primary or ischemic cardiomyopathy have viable and noncontractile myocardium. This may be related to numerous and perhaps overlapping factors, such as chronic ischemia (stunning/hibernation), neurohormonal abnormalities, oxidative stress, metabolic imbalances, and/or nutritional depletion. Changes in myocardial substrate utilization have adverse effects on the metabolism of the viable but noncontractile myocardium. Shifting the energy substrate preference away from fatty acids and replenishing the tricarboxylic acid cycle components via amino acids rather than via fatty acids would increase adenosine triphosphate production, with positive effects on cellular metabolism. A proposed study design is described and will be piloted through the Effects of Diatrofen on Myocardial Function in Patients with Chronic Heart Failure trial (D-CHF), an evaluation of an oral amino acid supplementation treatment in outpatients with heart failure.
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PMID:Effects of amino acid supplementation on left ventricular remodeling in patients with chronic heart failure with decreased systolic function and diabetes mellitus: rationale and design of a magnetic resonance imaging study. 1509 6

A 65-year-old patient with history of ischemic cardiomyopathy admitted to the hospital for chest pain and subsequently experienced incessant ventricular fibrillation (VF), requiring repeated defibrillation. Coronary angiogram was unchanged, compared to a study a year before, and acute ischemia was not considered to be the etiology of the VF. A particular premature ventricular contraction morphology was noted on telemetry prior to each episode of VF. The patient subsequently underwent successful radiofrequency ablation of a focus in the left ventricular free wall. Careful examination of initiating foci of VF or polymorphic ventricular tachycardia, with radiofrequency ablation in appropriate cases, could be potentially life-saving.
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PMID:Focal origin of ventricular fibrillation in a patient with ischemic cardiomyopathy. 1548 53

Williams syndrome is a complex syndrome comprising developmental abnormalities, craniofacial dysmorphic features, and cardiac anomalies. The most common cardiac anomaly is supravalvular aortic stenosis. We report a case of a 6-year-old girl with Williams syndrome who presented with decompensated heart failure due to ischemic cardiomyopathy. Her only significant cardiac anomaly was severe stenosis of the left main coronary artery. She subsequently died despite surgical revascularization. Isolated coronary anomalies are rare in Williams syndrome but should be considered especially in the presence of heart failure or ischemia.
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PMID:Severe coronary artery disease in the absence of supravalvular stenosis in a patient with Williams syndrome. 1554 15


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