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)

Morbidity and mortality resulting from cardiotoxic complications of anticancer therapy is still unacceptably high. Despite advances in the understanding of the pathomechanisms of cardiotoxicity, in prevention and detection of these complications, progressive ventricular dysfunction in cancer survivors represents a great therapeutic problem. Ventricular dysfunction is a life-threatening complication particularly in patients treated with anthracycline cytostatics. Anthracycline-induced loss of myocytes leads to an inadequate ventricular hypertrophy, which produces a rise in left ventricular (LV) afterload and deterioration of ventricular contractility culminating in heart failure. Efficacy of angiotensin-converting enzyme (ACE) inhibitors for the treatment of asymptomatic and symptomatic LV dysfunction in various clinical settings has been confirmed in a number of controlled, randomized trials. Until now, there are only few published data supporting the use of ACE inhibitors to treat patients with ventricular dysfunction-induced by anthracyclines. Cardio-protection with ACE inhibitors in children and adolescents treated with anthracyclines in contrast to ACE inhibition in adults after anthracycline therapy is a controversial topic. Evidence from the recent follow up study indicates a progressive deterioration of left ventricular wall thinning in childhood cancer survivors treated with enalapril. The ongoing large controlled, double blind, randomized trials will provide an important information concerning the efficacy of ACE inhibitors to prevent progression of ventricular dysfunction in paediatric oncologic patients.
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PMID:[ACE inhibitors in the treatment of ventricular dysfunction caused by cardiotoxic cytostatics]. 1509 72

The mandatory use of pharmacotherapy in human heart failure (HF) impedes further study of natural history and remodeling mechanisms. We created a sheep model of chronic, severe, ischemic HF [left ventricular (LV) ejection fraction (LVEF) <35% stable over 4 wk] by selective coronary microembolization under general anesthesia and followed hemodynamic, energetic, neurohumoral, structural, and cellular responses over 6 mo. Thirty-eight sheep were induced into HF (58% success), with 23 sheep followed for 6 mo (21 sheep with sufficient data for analysis) after the LVEF stabilized (median of 3 embolizations). Early doubling of LV end-diastolic pressure persisted, as did increases in LV end-diastolic volume, LV wall stress, and LV wall thinning. Contractile impairment (LV end-systolic elastance, LV preload recruitable stroke work, and dobutamine-responsive contractile reserve) and diastolic dysfunction also remained stable. Cardiac mechanical energy efficiency did not recover. Plasma atrial natriuretic peptide levels remained elevated, but rises in plasma aldosterone and renin activity were transient. Collagen content increased 170%, the type I-to-III phenotype ratio doubled in the LV, but right ventricular collagen remained unaltered. Fas ligand cytokine levels correlated with expression of both caspase-3 and -2, suggesting a link in the apoptotic "death cascade." Caspase-3 activity also bore a close relationship to LV meridional wall stress calculated from echocardiographic and intraventricular pressure measurements. We concluded that the stability of chronic untreated severe ischemic HF depends on the recruitment of myocardial remodeling mechanisms that involve an interaction among hemodynamic load, contractile efficiency/energetics, neurohumoral activation, response of the extracellular matrix, wall stress, and the myocyte apoptotic pathway.
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PMID:Remodeling of the chronic severely failing ischemic sheep heart after coronary microembolization: functional, energetic, structural, and cellular responses. 1514 56

Dilated cardiomyopathies (DCM) are due to progressive dilatation of the cardiac cavities and thinning of the ventricular walls and lead unavoidably to heart failure. They represent a major cause for heart transplantation and, therefore, defining an efficient symptomatic treatment for DCM remains a challenge. We have taken advantage of the hamster strain CHF147 that displays progressive cardiomyopathy leading to heart failure to test whether stimulation of a hypertrophic pathway could delay the process of dilatation.Six month old CHF147 hamsters were treated with IGF-1 so that we could compare the efficacy of systemic administration of human recombinant IGF-1 protein (rh IGF-1) at low dose to that of direct myocardial injections of a plasmid DNA containing IGF-1 cDNA (pCMV-IGF1).IGF-1 treatment did not induce a significant variation of ventricle mass, but preserved left ventricular (LV) wall thickness and delayed dilatation of cardiac cavities when compared to non-treated hamsters. Together with this reduction of dilatation, we also noted a reduction in the amount of interstitial collagen. Furthermore, IGF-1 treatment induced beneficial effects on cardiac function since treated hamsters presented improved cardiac output and stroke volume, decreased end diastolic pressure when compared to nontreated hamsters and also showed a trend towards increased contractility (dP/dt(max)).This study provides evidence that IGF-1 treatment induces beneficial structural and functional effects on DCM of CHF147 hamsters, hence making this molecule a promising candidate for future gene therapy of heart failure due to DCM.
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PMID:Administration of insulin-like growth factor-1 (IGF-1) improves both structure and function of delta-sarcoglycan deficient cardiac muscle in the hamster. 1561 44

A 64-year-old woman was transferred to the intensive care unit with dyspnea and palpitation on effort. Chest x-ray film showed cardiomegaly and pulmonary congestion. We carefully examined for sarcoidosis as a differential diagnosis of heart failure. Serum lysozyme was mildly high, but human atrial natriuretic peptide (HANP) and brain natriuretic peptide (BNP) were strikingly high. Angiotensin converting enzyme was within normal limit. Chest roentgenogram did not reveal bilateral hilar lymphadenopathy. Atrioventricular conduction block was not observed on electrocardiogram. Echocardiographic examination showed left ventricular global hypokinesis with septal thinning and enlargement. Mitral valve regurgitation was recognized by Doppler evaluation. Coronary arteriography showed normal coronary arteries. Endomyocardial biopsy revealed noncaseous epithelioid granulomas containing, Langhans type giant cell accompanied by fibrosis and lymphocyte infiltration. From these data cardiac sarcoidosis was diagnosed. Gallium scintigraphy showed diffuse uptake only in the heart. Treatment with oral prednisolone 20 mg/day was started. Her symptoms improved by several weeks after the medical treatment. In addition, both the value of HANP and BNP were markedly decreased and echocardiogram showed improvement of cardiac systolic function. In Japan, there is a higher incidence of cardiac sarcoidosis than in the West. The prognosis of this condition associated with cardiac dysfunction is reported to be very poor. When progressive heart failure in older patients is seen, cardiac sarcoidosis should also be kept in mind. Endomyocardial biopsy play an important role as the only accurate technique for the diagnosis of cardiac sarcoidosis.
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PMID:[A case of sarcoidosis in which sarocoid granulomas were observed only in the heart]. 1598 67

End-stage hypertrophic cardiomyopathy (ES-HCM), affecting 5-10% of human hypertrophic cardiomyopathy (HCM) patients, is characterized by relative thinning of the ventricular walls and septum with dilation of the ventricular lumen, decreased fractional shortening, and progression to heart failure. C. J. Baty and others recently documented similar progressive changes to ES-HCM in a family of four cats through serial echocardiograms. At the time of heart failure, these cats exhibited changes similar to those exhibited by human ES-HCM patients. Our objectives were to describe the pathologic alterations associated with ES-HCM and investigate the pathogenesis in three of the four cats. Grossly, there was left atrial dilation with relative thinning of the interventricular septum (IVS) and left ventricular free wall (LVFW). The left atrium contained large thrombi in two of the three cats, and all three cats died following thromboembolization of the aortic bifurcation. Histologically, all three cats had subendocardial and myocardial fibrosis, predominantly of the IVS and LVFW, and one cat had acute, multifocal, myocardial infarcts with mononuclear inflammatory cell infiltrates. The pathogenesis of ES-HCM is uncertain, but theories implicate occlusion of the coronary blood flow by thickening of the coronary vessels, coronary vascular thromboembolism or coronary vessel spasm, apoptosis of myocytes, and myocardial hypertrophy beyond the ability of the vasculature to supply blood. Apoptosis assays did not reveal any apoptotic myocytes. Considering the hypercoagulative state of these cats, coronary vascular thromboembolism could be a major contributing factor. We cannot exclude apoptosis or coronary vessel spasm on the basis of the data presented.
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PMID:Pathology of end-stage remodeling in a family of cats with hypertrophic cardiomyopathy. 1600 5

This review discusses current understanding of the role that endogenous and exogenous progenitor cells may have in the treatment of the diseased heart. In the last several years, a major effort has been made in an attempt to identify immature cells capable of differentiating into cell lineages different from the organ of origin to be employed for the regeneration of the damaged heart. Embryonic stem cells (ESCs) and bone marrow-derived cells (BMCs) have been extensively studied and characterized, and dramatic advances have been made in the clinical application of BMCs in heart failure of ischemic and nonischemic origin. However, a controversy exists concerning the ability of BMCs to acquire cardiac cell lineages and reconstitute the myocardium lost after infarction. The recognition that the adult heart possesses a stem cell compartment that can regenerate myocytes and coronary vessels has raised the unique possibility to rebuild dead myocardium after infarction, to repopulate the hypertrophic decompensated heart with new better functioning myocytes and vascular structures, and, perhaps, to reverse ventricular dilation and wall thinning. Cardiac stem cells may become the most important cell for cardiac repair.
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PMID:Cardiac stem cells and mechanisms of myocardial regeneration. 1618 16

The cellular signaling pathways responsible for the transition from compensated left ventricular hypertrophy (LVH) to LV dilatation (remodeling) and heart failure are unclear. As chronic administration of a beta-adrenoreceptor (beta-AR) agonist mediates the premature onset of cardiac remodeling without myocyte necrosis or myocardial dysfunction in LVH, we suggest that beta-AR activation is critical in promoting the transition from compensated LVH to cardiac dilatation. However, beta-AR mediated effects in the heart can occur via either the cyclic adenosine monophosphate (cAMP) system or via cAMP independent signaling pathways. To determine the role of cAMP in promoting adverse cardiac chamber remodeling, we evaluated whether phosphodiesterase inhibition (PDEI) promotes LV dilatation in rats with compensated LVH. The impact of chronic administration of the PDEI, pentoxifylline, on LV remodeling and function was assessed in spontaneously hypertensive rats (SHR) with compensated LVH. The PDEI mediated inotropic effects and increased cAMP concentrations in SHR. This dose of the PDEI administered for 4 months to SHR did not modify LV weight or influence intrinsic myocardial systolic function (as assessed in the absence of the PDEI) in SHR. However, the PDEI mediated the development of a right shift in LV end diastolic (LVED) pressure-internal dimension and LVED pressure-volume relations, LV wall thinning, and increments in myocardial soluble (non-cross-linked) collagen concentrations. In conclusion, chronic PDEI administration induces adverse geometric and interstitial cardiac remodeling in SHR, a finding that supports the notion that the beta-AR-cAMP system is important in mediating the progression to heart failure by promoting interstitial remodeling and LV dilatation in LVH.
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PMID:Phosphodiesterase inhibition promotes the transition from compensated hypertrophy to cardiac dilatation in rats. 1621 67

The chronic elevation in ventricular wall stress secondary to ventricular volume or pressure overload leads to structural remodeling of the muscular, vascular and extracellular matrix components of the myocardium. While initially a compensatory response, the progressive hypertrophy and ventricular dilatation induced by this condition ultimately have a detrimental effect on ventricular function, resulting in heart failure. Fibrillar collagen provides the skeletal framework which interconnects the cardiomyocytes, thereby maintaining ventricular shape and size and contributing to tissue stiffness. Accordingly, these myocardial collagen fibers must be disrupted for ventricular dilatation, sphericalization and wall thinning to occur. The presence of an abundant, latent matrix metalloproteinase (MMP) population which coexists with myocardial fibrillar collagen has been documented. Thus, the potential for collagen degradation to exceed synthesis exists should there be significant activation of this latent MMP system. Mast cells are known to store and release a variety of biologically active mediators including TNF-alpha and proteases such as tryptase and chymase, which can induce MMP activation. Increased cardiac mast cell density has been implicated in the pathophysiology of human end-stage cardiomyopathy and experimental myocardial infarction, hypertension and chronic volume overload secondary to mitral regurgitation and aorto-caval fistula. The potential role of cardiac mast cells in activating MMPs, which then results in fibrillar collagen degradation and adverse myocardial remodeling secondary to chronic volume and pressure overload will be the subject of this review.
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PMID:Cardiac mast cell regulation of matrix metalloproteinase-related ventricular remodeling in chronic pressure or volume overload. 1637 24

Although classic Fabry's disease results in multiple causes of death, the cardiac variant of Fabry's disease affects only the cardiac system and results in initial symmetric left ventricular (LV) hypertrophy and later LV dysfunction, asymmetric basal posterior LV wall thinning, restrictive mitral flow, and functional mitral regurgitation with end-stage chronic heart failure (CHF), leading to death. The purpose of this study was to investigate whether these findings predict prognoses in patients with cardiac Fabry's disease. In 13 consecutive men with cardiac Fabry's disease, LV wall thickness, the ejection fraction, mitral E-wave deceleration time, the LV Tei index, and functional mitral regurgitation were measured by echocardiography. Patients were followed for 5 to 96 months (mean 41 +/- 9). Eight patients developed New York Heart Association class III CHF, and 6 experienced cardiac death. A LV Tei index >0.60 and basal posterior LV wall thinning with a ratio of ventricular septal to posterior wall thickness >1.3 significantly preceded CHF and death (Tei index: 4.4 and 5.1 years; posterior wall thinning: 4.0 and 4.7 years), respectively (p <0.05). In conclusion, an increased LV Tei index and asymmetric basal posterior LV wall thinning are important echocardiographic findings that precede CHF and cardiac death in patients with cardiac Fabry's disease.
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PMID:Significance of asymmetric basal posterior wall thinning in patients with cardiac Fabry's disease. 1722 30

Macrophages have been suggested to be beneficial for myocardial wound healing. We investigated the role of macrophages in myocardial wound healing by inhibition of macrophage infiltration after myocardial injury. We used a murine cryoinjury model to induce left ventricular damage. Infiltrating macrophages were depleted during the 1st week after cryoinjury by serial intravenous injections of clodronate-containing liposomes. After injury, the presence of macrophages, which secreted high levels of transforming growth factor-beta and vascular endothelial growth factor-A, led to rapid removal of cell debris and replacement by granulation tissue containing inflammatory cells and blood vessels, followed by myofibroblast infiltration and collagen deposition. In macrophage-depleted hearts, nonresorbed cell debris was still observed 4 weeks after injury. Secretion of transforming growth factor-beta and vascular endothelial growth factor-A as well as neovascularization, myofibroblast infiltration, and collagen deposition decreased. Moreover, macrophage depletion resulted in a high mortality rate accompanied by increased left ventricular dilatation and wall thinning. In conclusion, infiltrating macrophage depletion markedly impairs wound healing and increases remodeling and mortality after myocardial injury, identifying the macrophage as a key player in myocardial wound healing. Based on these findings, we propose that increasing macrophage numbers early after myocardial infarction could be a clinically relevant option to promote myocardial wound healing and subsequently to reduce remodeling and heart failure.
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PMID:Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. 1732 68


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