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

Diabetes mellitus is associated with a specific cardiomyopathy. This is evident from the clinical-pathological work and the epidemiologic data from the Framingham study. Noninvasive studies of diabetics have shown alterations in systolic and diastolic function that may ultimately lead to clinical heart failure. The relationship of these cardiac changes to the type of diabetes, its duration, and its severity is not settled. However, a correlation between changes in heart function and other complications of diabetes has been demonstrated. Insufficient prospective data is available from noninvasive studies to establish the frequency of progression from subclinical cardiac dysfunction to overt congestive failure. The pathogenesis of this disorder is still uncertain. Pathological studies have shown changes in the intramural arteries, arterioles, and capillaries but their functional significance is uncertain. Experimental studies have shown interstitial changes leading to an apparently less compliant left ventricle in the diabetic dog and monkey. In the diabetic rat reversible changes were found in myocardial function, related to changes in contractile proteins and intracellular calcium metabolism. In both species, the response to anoxia or ischemia was altered in the presence of diabetes. However, irreversible depression of the contractile element was not found in most animal studies of isolated diabetes. In contrast, the combination of hypertension and diabetes leads to substantial cardiac damage and circulatory congestion, both in clinical and experimental investigations. Clearly much more work must be carried out to understand the pathogenesis, treatment, and ultimately the prevention of diabetic cardiomyopathy.
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PMID:Diabetic cardiomyopathy. 388 Sep 19

Cardiovascular complications are the most common causes of morbidity and mortality in diabetic patients. Coronary atherosclerosis is enhanced in diabetics, whereas myocardial infarction represents 20% of deaths of diabetic subjects. Furthermore, re-infarction and heart failure are more common in the diabetics. Diabetic cardiomyopathy is characterized by an early diastolic dysfunction and a later systolic one, with intracellular retention of calcium and sodium and loss of potassium. In addition, diabetes mellitus accelerates the development of left ventricular hypertrophy in hypertensive patients and increases cardiovascular mortality and morbidity. Treating the cardiovascular problems in diabetics must be undertaken with caution. Special consideration must be given with respect to the ionic and metabolic changes associated with diabetes. For example, although ACE inhibitors and calcium channel blockers are suitable agents, potassium channel openers cause myocardial preconditioning and decrease the infarct size in animal models, but they inhibit the insulin release after glucose administration in healthy subjects. Furthermore, potassium channel blockers abolish myocardial preconditioning and increase infarct size in animal models, but they protect the heart from the fatal arrhythmias induced by ischemia and reperfusion which may be important in diabetes. For example, diabetic peripheral neuropathy usually presents with silent ischemia and infarction. Mechanistically, parasympathetic cardiac nerve dysfunction, expressed as increased resting heart rate and decreased respiratory variation in heart rate, is more frequent than the sympathetic cardiac nerve dysfunction expressed as a decrease in the heart rate rise during standing.
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PMID:Diabetes mellitus and cardiac function. 954 31

Hyperglycemia alters cardiac function and often leads to diabetic cardiomyopathy as cardiomyocyte apoptosis causes a hypertrophied heart to deteriorate to dilation and failure. Paradoxically, many short-term animal models of hyperglycemia protect against ischemia-induced damage, including apoptosis, by limiting Ca(2+) overload. We have determined that, like nonexcitable cells, both neonatal and adult cardiomyocytes respond to depletion of sarcoplasmic/endoplasmic reticulum Ca(2+) stores with an influx of extracellular Ca(2+) through channels distinct from voltage-gated Ca(2+) channels, a process termed capacitative Ca(2+) entry (CCE). Here, we demonstrate that in neonatal rat cardiomyocytes, hyperglycemia decreased CCE induced by angiotensin II or the Ca(2+)ATPase inhibitor thapsigargin. Hyperglycemia also significantly blunted Ca(2+)-dependent hypertrophic responses by approximately 60%, as well as the Ca(2+)-sensitive nuclear translocation of a chimeric protein bearing the nuclear localization signal of a nuclear factor of activated T-cells transcription factor. The attenuation of CCE by hyperglycemia was prevented by azaserine, an inhibitor of hexosamine biosynthesis, and partially by inhibitors of oxidative stress. This complements previous work showing that increasing hexosamine metabolites in neonatal cardiomyocytes also inhibited CCE. The inhibition of CCE by hyperglycemia thus provides a likely explanation for the transition to diabetic cardiomyopathy as well as to the protection afforded to injury after ischemia/reperfusion in diabetic models.
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PMID:Hyperglycemia inhibits capacitative calcium entry and hypertrophy in neonatal cardiomyocytes. 1245

Although kinins have been associated with the regulation of cardiovascular function in left ventricular hypertrophy (LVH) as a consequence of hypertension, myocardial infarction (MI), and/or diabetic cardiomyopathy, less is known about their receptor regulation under these conditions. We have therefore investigated the bradykinin B1-receptor (B1R) and B2-receptor (B2R) mRNA expression in rat models of MI, LVH and diabetes mellitus (DM). Sprague-Dawley rats (SD) were submitted to permanent ligation of the left descending coronary artery (LAD) to induce a MI, whereas DM was induced by a single injection of streptozotocin (STZ). LVH was induced after thoracic aortic banding (AB). Three weeks after MI, six weeks after STZ injection or six weeks after AB, left ventricular (LV) function was characterized using a Millar-tip catheter. Cardiac B1R- and B2R-mRNA expression were analyzed by specific RNase-protection assays (RPA). LV contractility (dP/dt max) was impaired by 40-48% in rats after induction of MI or DM compared to their controls. However, despite an enormous increase in LV end-diastolic pressure (LEVDP) to 310% after AB, LV contractility did not differ compared to the controls. These hemodynamic changes were accompanied by an up-regulation of cardiac B1R- (MI, 288%; STZ, 215%; AB, 4180%) and B2R-mRNA expression (MI, 122%; STZ, 288%; AB, 96%). Up-regulation of both BK-receptor (BKR) types in early stages of cardiac wound healing induced by ischemia and in chronic stages of cardiac remodeling induced by pressure-overload or by hyperglycemia indicates that kinins play a major role in the complex processes of cardiac tissue injury and repair.
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PMID:Regulation of cardiac bradykinin B1- and B2-receptor mRNA in experimental ischemic, diabetic, and pressure-overload-induced cardiomyopathy. 1248 96

Myocardial cell death is a key element in the pathogenesis and progression of various etiological cardiomyopathies such as ischemia-reperfusion, toxic exposure, and various chronic diseases including myocardial infarction, atherosclerosis, and endothelial dysfunction. Myocardial cell death is also observed in the hearts of diabetic patients and animal models; however, its importance in the development of diabetic cardiomyopathy is not completely understood. The goal of this review is to summarize our current understanding of the characteristics of diabetes-induced myocardial cell death. In the search of the mechanisms by which diabetes induces myocardial cell death, multiple cell death pathways have been proposed. Reactive oxygen and nitrogen species accumulation plays a critical role in the cell death process. Several studies have shown that suppression of myocardial cell death by antioxidants or inhibitors for apoptosis-specific signaling pathways results in a significant prevention of diabetic cardiotoxicity, suggesting that cell death in diabetic subjects plays an important role in the development of diabetic cardiomyopathy.
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PMID:Cell death and diabetic cardiomyopathy. 1455 88

Although many aspects of cardiovascular disease are similar between women and men, it is becoming increasingly obvious that there are significant differences as well. Premenopausal women usually have a lower risk of cardiovascular diseases than age-matched men and postmenopausal women. However, the "female advantage" disappears once women are afflicted with diabetes mellitus. Heart diseases are twice as common in diabetic men and five times as common in diabetic women. It is believed that differences in sex hormones and intrinsic myocardial and endothelial functions between men and women may be responsible for this female "advantage" and "disadvantage" in normal and diabetic conditions. Most experimental and clinical studies on diabetes only included male subjects and failed to address this important gender difference in diabetic heart complications. Although female hearts may be better tolerated to stress (such as ischemia) insults than their male counterparts, female sex hormone such as estrogen may interact with certain risk factors under diabetes which may compromise the overall cardiac function. The benefit versus risk of estrogen replacement therapy on cardiac function and overall cardiovascular health in diabetes remains controversial. This review will focus on gender-related difference in diabetic heart complication--diabetic cardiomyopathy--and if gender differences in intrinsic myocardial contraction, polyol pathway metabolism, and advanced glycation endproduct formation and other neuroendocrinal regulatory mechanisms to the heart may contribute to disparity in diabetic cardiomyopathy between men and women.
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PMID:Diabetic cardiomyopathy: do women differ from men? 1571 Oct 18

The phospholipases associated with the cardiac sarcolemmal (SL) membrane hydrolyze specific membrane phospholipids to generate important lipid signaling molecules, which are known to influence normal cardiac function. However, impairment of the phospholipases and their related signaling events may be contributory factors in altering cardiac function of the diseased myocardium. The identification of the changes in such signaling systems as well as understanding the contribution of phospholipid-signaling pathways to the pathophysiology of heart disease are rapidly emerging areas of research in this field. In this paper, I provide an overview of the role of phospholipid-mediated signal transduction processes in cardiac hypertrophy and congestive heart failure, diabetic cardiomyopathy, as well as in ischemia-reperfusion. From the cumulative evidence presented, it is suggested that phospholipid-mediated signal transduction processes could serve as novel targets for the treatment of the different types of heart disease.
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PMID:Phospholipid-mediated signaling systems as novel targets for treatment of heart disease. 1748 43

Patients in different stages of diabetic nephropathy (DN) frequently present cardiac disease expressed by myocardial ischemia and/or diabetic cardiomyopathy. These changes are already present at early stages of DN, probably even before urinary albumin excretion (UAE) reaches the traditionally diagnostic levels of microalbuminuria. The cardiac changes are responsible for a significant proportion of the increased death rates in patients with DN and can be reduced through multiple intervention on the several risk factors present in these patients. Cardiac disease assessment should ideally be performed in every patient, irrespective of renal status, through specific methods to detect ischemia and myocardial dysfunction, besides routinely performing 24-h ambulatory blood pressure monitoring. In patients with advanced atherosclerosis, other arteries (aorta, carotid, renal) should be evaluated as well. Intensive treatment of arterial hypertension, and use of cardioprotective drugs, correction of the associated dyslipidemia and anemia, and use of antiplatelet agents can reduce the elevated cardiovascular mortality in patients with DN.
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PMID:[Diabetic nephropathy and cardiac disease]. 1750 31

Heart disease is the leading cause of death in patients with insulin resistance and type 2 diabetes (DM2). Even in the absence of coronary artery disease and hypertension, functional and structural abnormalities exist in patients with well-controlled and uncomplicated DM2. These derangements are collectively designated by the term diabetic cardiomyopathy (DCM). Changes in myocardial energy metabolism, due to altered substrate supply and utilization, largely underlie the development of DCM. Insulin is an important regulator of myocardial substrate metabolism, but also exerts regulatory effects on intracellular Ca2+ handling and cell survival. The current paper reviews the multiple functional and molecular effects of insulin on the heart, all of which ultimately seem to be cardioprotective both under normal conditions and under ischemia. In particular, the dismal consequences of myocardial insulin resistance contributing to the development of DCM will be discussed.
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PMID:Myocardial insulin action and the contribution of insulin resistance to the pathogenesis of diabetic cardiomyopathy. 1755 6

Glucose metabolism plays an important role in cardiac bioenergetics that changes under various stress conditions including hypertrophy, diabetic cardiomyopathy, and ischemia-reperfusion injury. To understand the role of glycolysis under these conditions, we have altered several steps of the glycolytic pathway specifically in the heart. In this chapter, we describe methods used to produce cardiac-targeted transgenic mice and procedures for measuring various glucose metabolites including glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate, and glycogen. Also, we describe methods for measuring glucose transport and glycolysis in perfused mouse hearts. Using these methods, we show that mice over-expressing cardiac-specific kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (Mykd-PFK-2) show reduced glucose transport and reduced glycolysis when compared with control. The metabolites glucose-6-phosphate, fructose-6-phosphate, and glycogen were elevated, whereas fructose-1,6-bisphosphate was reduced in the transgenic Mykd-PFK-2 mouse hearts.
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PMID:Altering and analyzing glucose metabolism in perfused hearts of transgenic mice. 1828 70


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