Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular structural remodeling is the compensatory response of the tissue following pathological stage. Myocardial infarction, which leads to adverse remodeling, thinning of the ventricle wall, dilatation and heart failure, is one of the leading causes of death. Remodeling implies an alteration in the extracellular matrix and in the spatial orientation of cells and intracellular components. The extracellular matrix is responsible for cardiac cell alignment and myocardial structural integrity. Substances that break down the extracellular matrix, specialized proteinases as well as inhibitors of proteinases, appear to be normally balanced in maintaining the integrity of the myocardium. Myocardial infarction leads to an imbalance in proteinase/antiproteinase activities causing alterations in the stability and integrity of the extracellular matrix and adverse tissue remodeling. To explore mechanisms involved in this process and, in particular, to focus on matrix metalloproteinases, their inhibitors, and activators, an understanding of proteinase and antiproteinase is needed. This review represents new and significant information regarding the role of activated matrix proteinases antiproteinases in remodeling. Such information will have a significant impact both on the understanding of the basic cell biology of extracellular matrix turnover, as well as on potential avenues for pharmacological approaches to the treatment of ischemic heart disease and failure.
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PMID:Proteinases and myocardial extracellular matrix turnover. 906 88

Most patients with implantable defibrillators have diminished cardiac function. Progressive heart failure might impair defibrillation efficacy, leading to interpreted device failure. This study sought to determine the effect of ventricular dysfunction on defibrillation energy using a biphasic endocardial system. Eleven dogs were ventricularly paced at 225 pulses/min for 2 weeks to induce ventricular dysfunction, and five control dogs remained unpaced. Dose response defibrillation probability curves were generated for each animal at baseline, after 2 weeks (at which time the pacemakers were turned off in the paced group), and then 1 week later. The defibrillation thresholds, ED20, ED50, and ED80 (the 20%, 50%, and 80% effective defibrillation energies, respectively) were determined for each dog at each study. In the paced dogs, the mean ejection fraction fell from 55% to 25% after pacing (P < 0.0001), and rose to 46% after its discontinuation (P = 0.0002). The defibrillation threshold, ED20, ED50, and ED80 remained unchanged in both the control and paced groups for all three studies, even after adjustment for dog weight or left ventricular mass. Rapid pacing produced no change in left ventricular mass. It induced ventricular cavity dilatation and wall thinning, which had opposing effects on defibrillation energy requirements, resulting in no net change of the ED50 in heart failure. In conclusion, the defibrillation efficacy of a biphasic transvenous system is not changed by the development of heart failure using the rapid paced canine model.
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PMID:Stability of the defibrillation probability curve with the development of ventricular dysfunction in the canine rapid paced model. 950 35

Coronary artery diseases may categorized into asymptomatic disease, angina pectoris, myocardial infarction, chronic heart failure, and sudden coronary death. Unstable angina, acute myocardial infarction, and sudden cardiac death are known as the acute coronary syndromes. Coronary atheroma is unstable in the patients with acute coronary syndromes. Stable plaques will be unstable when dynamic alterations occur. The alterations are plaque rupture, plaque hemorrhage, coronary thrombosis and vasospasm. They act each other. We analysed the histopathology of coronary arteries who died of acute myocardial infarction in 85 cases. It showed that the risk factors of plaque rupture are clusters of form cells, eccentric plaque with soft lipid rich core, and thinning of fibrous cap in atheroma. Most of these cases ruptured at edge of the atheroma.
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PMID:[Pathogenesis of acute coronary syndromes]. 978 Jul 33

There is now little doubt that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) play a role in cardiac development and in cardiovascular physiology in adult life. Congenital lack of GH is associated with defective cardiac growth, ventricular wall thinning, and impaired systolic function. These abnormalities limit exercise capacity and contribute to the poor quality of life in patients with GH deficiency. In addition, studies with in vitro muscle preparations have shown that IGF-1 affects myocardial contractility by a direct mechanism. These findings suggested that GH would benefit patients affected by heart failure. Indeed, GH and/or IGF-1 have proven beneficial in various models of experimental heart failure. Tested in patients with classes II-IV heart failure, they improved cardiac performance and clinical status. These effects were associated with improved myocardial energetics and de-activation of the neurohormonal system. Because of the uncontrolled nature of the studies and the small number of cases examined, conclusions as to the effectiveness of GH and IGF-1 must await the results from larger trials.
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PMID:Growth hormone: a new therapy for heart failure? 1008 93

A 4-month-old girl presented with 2 weeks of symptoms and physical signs of heart failure. Echocardiography demonstrated marked left ventricular dilation, thinning of the myocardium with anterolateral akinesis, mitral regurgitation, a moderate pericardial collection, and an anomalous left coronary artery from the pulmonary artery. At operation there was a tense hemopericardium and a site of imminent rupture through a transmural anterior infarction. The anomalous artery was reimplanted in the ascending aorta, and an extensive infarct resection and ventricular repair performed. Support with a left ventricular assist device was required for 3 days, but the infant subsequently made a satisfactory recovery. Left ventricular rupture is a very rare complication of this lesion, but should be considered if there is evidence of a pericardial collection.
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PMID:Incipient left ventricular rupture complicating anomalous left coronary artery. 1008 69

To investigate how insulin-like growth factor I (IGF-I) modulates cardiovascular function and myocardial apoptosis in heart failure, the therapeutic effects of IGF-I were determined in a canine model of dilated cardiomyopathy. The animals were paced at 220 beats/min, and the left ventricular (LV) chamber became dilated after 2 weeks. A subset of paced dogs was treated with s.c. injections of IGF-I from week 3 to week 4. After 4 weeks of pacing, untreated paced dogs developed significant ventricular dysfunction. IGF-I-treated paced dogs showed better cardiac output, stroke volume, LV end-systolic pressure, and LV end-diastolic pressure. Moreover, pulmonary wedge pressure and systemic vascular resistance were increased in the untreated group and decreased in the IGF-I-treated group. IGF-I treatment was associated with less thinning of the ventricular wall. Compared with the controls, untreated paced dogs showed increased apoptosis of cardiac muscle cells, which was partially suppressed by IGF-I treatment. The myocardial apoptotic index was negatively related to the thickness of the ventricular wall and to cardiac output, suggesting that ventricular remodeling/dysfunction involves the occurrence of myocardial apoptosis. Due to the close resemblance between this experimental model of dilated cardiomyopathy and human heart failure, the results of this study provide evidence that IGF-I may be a potential therapeutic agent for the failing human heart.
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PMID:Insulin-like growth factor I improves cardiovascular function and suppresses apoptosis of cardiomyocytes in dilated cardiomyopathy. 1049 43

Dilated cardiomyopathy (DCM) is a heart muscle disorder characterized by atrial and ventricular dilation often with relative wall thinning, severe systolic and diastolic ventricular dysfunction, and frequent findings of heart failure. Using genetically engineered mice, a number of studies have attempted to determine the role of specific genes, as well as to mimic the phenotype of human DCM. Naturally occurring and acquired animal models of DCM also have been investigated. In this brief review, we will focus on small animal models of DCM, particularly those in the mouse, together with some comments on the autosomal-recessive cardiomyopathy of the hamster. These animal models can be categorized into several general groups in accordance with the presumed role of the gene mutation involved, including intrasarcomeric and extrasarcomeric cytoskeletal abnormalities, which resemble some forms of hereditary human DCM, and overexpression or disruption of genes that control molecules participating in intracellular signaling pathways, including the beta-adrenergic system and calcium regulation. Modifications in the latter two pathways can cause or alleviate DCM in animal models, suggesting their importance in myocyte adaptive and survival mechanisms.
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PMID:Models of dilated cardiomyopathy in the mouse and the hamster. 1095 28

Calcium channel antagonists (CCAs) have been proposed to prevent cardiac events after myocardial infarction (MI). However, unwanted effects, such as negative inotropy, limit their use in many cases. The aim of this study was to compare the effects of long-term treatment with the CCAs, mibefradil, verapamil, and amlodipine, administered before and after chronic MI on myocardial remodeling and cardiac function. MI was induced by permanent ligation of the left coronary artery in male Wistar rats. Infarcted animals were treated with placebo, mibefradil (10 mg/kg/d po), verapamil (8 mg/kg bid po), or amlodipine (4 mg/kg/d po). Treatment was started 7 days before or 3 h after MI induction. Six weeks after MI, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), and cardiac contractility (dP/dt(max)) were measured. Morphometric parameters such as infarct size (IS), left ventricular dilation (LVD), septal thickness (ST), and cardiac fibrosis were determined in picrosirius red-stained hearts. Six weeks after MI, MAP and dP/dt(max) were decreased, whereas LVEDP and HR were increased in placebo-treated controls. The hearts featured an IS of 45%, left ventricular dilation, cardiac fibrosis, and septal thinning. MAP of all CCA-treated animals was increased, whereas LVEDP was decreased and dP/dt(max) increased 7-day pre- and 3-h post-MI started in mibefradil- and amlodipine-treated animals, but not in verapamil-treated animals. In contrast to amlodipine treatment, before and after MI started mibefradil and verapamil treatment decreased HR. Pretreatment with all CCA reduced IS and increased ST, whereas only mibefradil and amlodipine pretreatment prevented LVD and cardiac fibrosis. After MI started treatment with mibefradil and amlodipine reduced IS and cardiac fibrosis, and increased ST. Long-term treatment with the CCAs mibefradil, verapamil, and amlodipine reduced myocardial remodeling and improved cardiac function in MI-induced heart failure in rats.
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PMID:Calcium channel blockade limits cardiac remodeling and improves cardiac function in myocardial infarction-induced heart failure in rats. 1115 76

Myocardial infarction (MI), leads to cardiac remodeling, thinning of the ventricle wall, ventricular dilation, and heart failure, and is a leading cause of death. Interactions between the contractile elements of the cardiac myocytes and the extracellular matrix (ECM) help maintain myocyte alignment required for the structural and functional integrity of the heart. Following MI, reorganization of the ECM and the myocytes occurs, contributing to loss of heart function. In certain pathological circumstances, the ECM is modulated such that the structure of the tissue becomes damaged. The matrix metalloproteinases (MMPs) are a family of enzymes that degrade molecules of the ECM. The present experiments were performed to define the time-course, isozyme subtypes, and cellular source of increased MMP expression that occurs following MI in an experimental rabbit model. Heart tissue samples from infarcted and sham animals were analyzed over a time-course of 1-14 days. By zymography, it was demonstrated that, unlike the sham controls, MMP-9 expression was induced within 24 hours following MI. MMP-3 expression, also absent in sham controls, was induced 2 days after MI. MMP-2 expression was detected in both the sham and infarcted samples and was modestly up-regulated following MI. Tissue inhibitor of metalloproteinase-1 (TIMP-1) expression was evaluated and shown to be down-regulated following MI, inverse of MMP-9 and MMP-3 expression. Further, MMP-9 and MMP-3 expression was detected by immunohistochemistry in myocytes within the infarct. Additional studies were conducted in which cultured rat cardiac myocytes were exposed to a hypoxic environment (2% O2) for 24 hours and the media analyzed for MMP expression. MMP-9 and MMP-3 were induced following exposure to hypoxia. It is speculated that the net increase in proteolytic activity by myocytes is a contributing factor leading to myocyte misalignment and slippage. Additional studies with a MMP inhibitor would elucidate this hypothesis.
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PMID:Matrix metalloproteinase expression in cardiac myocytes following myocardial infarction in the rabbit. 1120 71

The effect of glibenclamide and glimepiride, two orally active antidiabetic sulphonylurea derivatives, on the development of myocardial infarction has been compared. Permanent coronary artery ligation was induced in rats and the development of infarction was evaluated by a computer-assisted method after nitroblue-terazolium staining. Seven-day coronary ligation produced enlargement of the left ventricular cavity, scar thinning and thickening of the non-infarcted myocardium. Glibenclamide treatment (5 mg/kg b.i.d. intraperitoneally) decreased the infarct volume (29.1 +/- 3.5% vs. 39.1 +/- 3.2% in controls), that occurred primarily as a result of more significant thinning of the scar tissue (1.6 +/- 0.04 mm vs. 2.0 +/- 0.13 mm in controls). Glibenclamide also inhibited the thickening of the non-infarcted ventricular septum (2.1 +/- 0.10 mm vs. 2.9 +/- 0.10 mm in controls). In contrast to the effects of glibenclamide, glimepiride treatment (5 mg/kg b.i.d. intraperitoneally) inhibited the enlargement of the left ventricular cavity (15.2 +/- 1.1% vs. 19.9 +/- 1.2% of the left ventricular volume in controls), it did not precipitate scar thinning and did not influence the development of hypertrophy of the non-infarcted myocardium. These results suggest that glimepiride treatment might inhibit the development of left ventricular dilatation after myocardial infarction. Glibenclamide treatment, however, producing a thinning of the scar tissue may further precipitate morphological changes that can contribute to the development of heart failure.
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PMID:Effect of glibenclamide and glimepiride treatment on the development of myocardial infarction in rats. 1120 66


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