Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extent to which the impaired left ventricle dilates may have important prognostic implications for survival. To determine the influence of infarct size and duration on ventricular dilation, the passive pressure-volume relation of the left ventricle in the rat after coronary artery ligation was obtained. In the early (0.25 to 2 days) phase, the pressure-volume relation was relatively unchanged in all infarct-size groups, except for a rightward shift in the low pressure range for moderate and large infarcts and a leftward shift in the high pressure range for small infarcts. From 2 to 7 days, ventricular dilatation occurred in all groups in relation to infarct size. Thereafter (to 106 days), in rats with moderate and large infarcts, the left ventricle continued to dilate. Associated with this late dilation was a decrease in left ventricular chamber stiffness and an increase in the volume to mass ratio. To determine whether the potentially deleterious progression of ventricular dilation could be attenuated, the angiotensin-converting enzyme inhibitor captopril was given 2 or 21 days after infarction and continued for 3 months. There was a significant overall effect of this treatment in attenuating left ventricular dilation, which was most pronounced in moderate infarcts. Captopril not only attenuated the rightward shift of the pressure-volume relation, but also markedly lowered left ventricular filling pressures so that operating volumes in treated rats were considerably reduced compared with those in untreated rats, even in large infarcts. Therapy with captopril also had an overall effect in prolonging survival, the most benefit being observed in moderate infarcts with lesser dilated left ventricles.
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PMID:Progressive ventricular dilation in experimental myocardial infarction and its attenuation by angiotensin-converting enzyme inhibition. 183 94

Angiotensin-converting enzyme inhibitors have had a significant impact on the treatment of congestive heart failure (CHF). Hemodynamic and clinical improvements in patients with severe CHF fostered the use of angiotensin-converting enzyme inhibitors in mild to moderate CHF. Angiotensin-converting enzyme inhibitors produce acute and sustained improvements in ventricular hemodynamics and quality of life. Captopril plus diuretic therapy is an effective alternative to digoxin in patients with mild to moderate CHF. Enalapril maleate and lisinopril have been shown to be effective in moderate to severe CHF when combined with digoxin and diuretics. Captopril and enalapril also improve survival in selected patients; captopril attenuates left ventricular dilatation after myocardial infarction. Although all angiotensin-converting enzyme inhibitors are similar in mechanism of action, pharmacokinetic differences impact their clinical use. Prolonged symptomatic hypotension compromising systemic perfusion and organ function has been reported with longer-acting agents; hypotension is usually short-lived and rarely compromises organ function with shorter-acting agents.
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PMID:Angiotensin-converting enzyme inhibitors in congestive heart failure. 187 77

Several experimental studies have suggested that the sulphydryl-containing angiotensin-converting enzyme inhibitor, captopril, has cardioprotective effects in the setting of acute myocardial ischaemia, ischaemia/reperfusion and infarction. We have observed that captopril can reduce the degree of dilatation and early functional myocardial infarct expansion produced by 3 h of permanent coronary artery occlusion in anaesthetized, open-chest dogs. In addition, captopril has been shown to limit experimental infarct size, reduce the incidence of reperfusion arrhythmias, and improve contractile function of stunned myocardium. When administered chronically after myocardial infarction, both experimental and clinical evidence suggests that captopril reduces left ventricular dilatation. Captopril is currently being tested in large clinical trials as adjuvant therapy to thrombolysis.
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PMID:Cardioprotective effects of captopril in myocardial ischaemia, ischaemia/reperfusion and infarction. 219 13

Before efficacy of therapy has been proven in large populations years or decades may pass. Meanwhile the medical profession has to rely on probabilities. This holds true regarding improvement of prognosis of CHF by ACE inhibition. While symptomatic improvement of CHF by addition of ACE-inhibition. While symptomatic improvement of CHF by addition of ACE-inhibitors has been demonstrated in numerous studies, improvement of prognosis has not yet been demonstrated entirely sufficiently. Only one trial has been published so far in a severely ill but not very exactly defined population (66). Animal studies and several small or interim published trials, however, show that the positive influence of ACE-inhibitors on CHF pathophysiology and symptomatology might favourable affect the prognosis as well. The SAVE trial and the SOLVD trial - both have randomized several thousand patients - will give answers concerning the influence of Captopril and Enalapril on prognosis of symptomatic as well as asymptomatic left ventricular dysfunction and on progression of left ventricular dilatation. The VHEFT II trial will compare the effect of ACE-inhibitors with the combination of ISDN and Hydralazine. Results will be available within the first few years of this decade.
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PMID:[Heart insufficiency and life expectancy--the role of ACE inhibitors]. 240 50

The spontaneously hypertensive rat (SHR) exhibits both a compensated phase of cardiac hypertrophy in which forward output is maintained despite persistently elevated systemic arterial pressures and a decompensated phase in which cardiac performance has deteriorated in spite of further hypertrophic growth. To determine whether chronic antihypertensive therapy prevents the development of heart failure and the progression of cardiac hypertrophy in SHR with advanced hypertension, captopril (2 g/l of drinking water), a converting enzyme inhibitor, was administered to 14 month old female SHR and normotensive American Wistar rats (NWR) for 10 months. The severe left ventricular hypertrophy of the 24 month old untreated SHR (4.37 +/- 0.2 mg/g v. 2.50 +/- 0.06 mg/g, untreated NWR) was markedly reduced (P less than 0.02) by captopril (3.01 +/- 0.1 mg/g). Chronic therapy prevented the reduction of both baseline and maximal cardiac indices in SHR, but did not alter blood flow in NWR. Left ventricular dilatation was present in 24 month old SHR and, as peak stroke volume index was diminished, the ejection fraction index of the SHR was reduced. Captopril restored this index in SHR to normal. The relation of ejection fraction index and afterload (peak systolic wall stress) was depressed in untreated SHR, but was normal in treated SHR. Thus, chronic therapy with captopril prevented the development of severe cardiac dysfunction and produced a marked regression of cardiac hypertrophy in SHR with advanced hypertensive heart disease.
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PMID:Prevention of the development of heart failure and the regression of cardiac hypertrophy by captopril in the spontaneously hypertensive rat. 622 Aug 93

Spontaneously hypertensive rats (SHR) of advanced age exhibit depressed myocardial contractile function and ventricular fibrosis, as stable compensated hypertrophy progresses to heart failure. Transition to heart failure in SHR aged 18-24 months was characterized by impaired left ventricular (LV) function, ventricular dilatation, and reduced ejection fraction without an increase in LV mass. Studies of papillary muscles from SHR with failing hearts (SHR-F), SHR without failure (SHR-NF), and age-matched Wistar Kyoto (WKY) rats allowed examination of changes in the mechanical properties of myocardium during the transition to heart failure. Papillary muscles of SHR-F exhibited increased fibrosis, impaired contraction, and decreased myocyte fractional area. These findings in papillary muscles were correlated with a higher concentration of hydroxyproline and increased histological evidence of fibrosis in the LV free wall. While a depression in active tension accompanied these structural alterations in papillary muscles, it was not evident when active tension was normalized to myocyte fractional area. Together, these data suggest that individual myocyte function may be preserved but that myocyte loss and replacement by extracellular matrix contribute substantially to the decrement in active tension. An absent or negative inotropic response to isoproterenol is observed in SHR-F and SHR-NF papillary muscles and may result in part from age-related alterations in beta-adrenergic receptor dynamics and a shift from alpha- to beta-myosin heavy chain (MHC) protein. During the transition to failure, ventricles of SHR exhibit a marked increase in collagen and fibronectin mRNA levels, suggesting that an increase in the expression of specific extracellular matrix genes may contribute to fibrosis, tissue stiffness, and impaired function. Transforming growth factor-beta 1 (TGF-beta 1) mRNA levels also increase in SHR-F, consistent with the concept that TGF-beta 1 plays a key regulatory role in remodelling of the extracellular matrix gene during the transition to failure. The renin-angiotensin-aldosterone system is also implicated in the transition to failure: SHR treated with the angiotensin converting enzyme inhibitor captopril starting at 12 months of age did not develop heart failure during the 18-24 month observation period. Captopril treatment that was initiated after rats were identified with evidence of failure led to a reappearance of alpha-MHC mRNA but did not improve papillary muscle function. Research opportunities include investigation of apoptosis as a mechanism of cell loss, delineation of the regulatory roles of TGF-beta 1 and the renin-angiotensin-aldosterone system in matrix accumulation, and studies of proteinase cascades that regulate matrix remodelling.
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PMID:The ageing spontaneously hypertensive rat as a model of the transition from stable compensated hypertrophy to heart failure. 868 57