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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In both men and women left ventricular hypertrophy (LVH) is the major risk factor associated with the appearance of diastolic and/or systolic myocardial failure. It is not the growth of cardiac myocytes, however, that is responsible for an abnormal structural remodeling of the hypertrophied myocardium in pathologic LVH, but instead, nonmyocyte cells whose behavior and growth are altered by chronic elevations in circulating hormones. Hormone-mediated cardiac fibroblast proliferation and/or enhanced collagen synthesis, for example, account for myocardial fibrosis. The signals mediating nonmyocyte cell involvement in LVH may also involve locally generated hormones having paracrine properties. Herein we review experimental findings pertaining to the reparative and reactive fibrosis of the myocardium seen in various forms of acquired and genetic arterial hypertension, where circulating or tissue renin-angiotensin-aldosterone systems are respectively activated. These hormonal systems determine whether myocardial structure will be altered in arterial hypertension and, accordingly, if myocardial failure ensues. The mechanisms by which these hormones lead to myocardial fibrosis remain to be elucidated and correspondingly will determine if fibrosis can be effectively prevented. At the same time, experimental strategies that regress excess collagen in LVH have been identified, but need to be developed further to determine if myocardial failure, caused by fibrosis, is indeed reversible in humans.
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PMID:Myocardial fibrosis and the renin-angiotensin-aldosterone system. 138 Jun 19

The pharmacokinetics of synthetic atrial natriuretic factor (ANF) and its effects on cyclic GMP, urinary sodium excretion, and hemodynamics were compared in 18 control subjects with normal hemodynamics and 12 patients with severe heart failure. Human 99-126 ANF was administered intravenously (0.2 micrograms/kg i.v. followed by 0.07 micrograms/kg/min for 30 min). As compared with controls, baseline plasma ANF concentration was higher in the heart failure group (329.2 +/- 166.1 vs. 33.6 +/- 17.3 pg/ml in controls, means +/- SD, p less than 0.01). Synthetic ANF increased plasma ANF concentration by similar amounts, but the elimination half-life (t 1/2) for synthetic ANF was longer in the heart failure group (6.5 +/- 2.6 vs. 3.8 +/- 0.8 min, p less than 0.05). Baseline plasma cyclic GMP concentration was higher in the heart failure group (13.8 +/- 6.8 vs. 4.2 +/- 2.2 pmol/ml, p less than 0.01) but ANF increased plasma cyclic GMP concentration to a lesser degree (14.4 +/- 7.6 pmol/ml, p less than 0.05 vs. 24.9 +/- 10.1 pmol/ml, p less than 0.001). Baseline urinary sodium excretion was less in the heart failure group (13.3 +/- 14.0 vs. 53.7 +/- 37.3 mumol/min, p less than 0.01) and ANF induced a smaller increase in urinary sodium excretion (22.1 +/- 32.3 mumol/min, p less than 0.05 vs. 305.7 +/- 242.9 mumol/min, p less than 0.001). Baseline plasma norepinephrine (NE), renin, and aldosterone were higher in the heart failure group. Synthetic ANF increased plasma NE only in the control group, had no effect on renin, and decreased aldosterone in both groups. Hemodynamic responses were similar in both groups except the decreased arterial blood pressure (BP) was accompanied by increased heart rate (HR) only in the controls. Therefore, in heart failure, the t 1/2 of ANF is prolonged and there appears to be a limit for further increase in cyclic GMP. These changes may explain in part the blunted renal response to ANF.
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PMID:Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure. 138 66

The basis for impaired left ventricular function of hearts in moderate to severe stages of hypertrophy and congestive heart failure remains uncertain. At the cellular level, the mechanisms governing the movements of calcium in the myocardium are actually depressed and might at least in part account for the slowing of the maximum shortening velocity and the impaired relaxation. These alterations of membrane proteins seem particularly important in species where the slowing of Vmax cannot be a consequence of the myosin heavy chain shift. They lead to an unstable equilibrium of calcium homeostasis and to calcium overload in heart failure. On the other hand, the enhanced density and remodeling of collagen in the hypertrophied heart, which would depend on elevation in circulating aldosterone, impair myocardial stiffness with diastolic dysfunction and lead to altered pumping capacity of the heart. Disturbances of calcium metabolism and matrix collagen remodeling enhance early afterdepolarizations and arrhythmias.
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PMID:Remodeling of the heart (membrane proteins and collagen) in hypertensive cardiopathy. 138 39

Candoxatril is a novel, orally active inhibitor of neutral endopeptidase EC 3.4.24.11, the enzyme that degrades atrial natriuretic peptide (ANP). The acute and chronic (10 days treatment) hemodynamic and hormonal effects of candoxatril (150 mg twice daily) in 12 patients with moderately severe congestive heart failure were investigated in a randomized, placebo-controlled, double-blind study. On study day 1, candoxatril acutely increased plasma ANP levels, suppressed aldosterone and decreased right atrial and pulmonary capillary wedge pressures. After 10 days of treatment, basal ANP was increased and basal aldosterone was decreased. Body weight was reduced, most likely reflecting chronic natriuretic or diuretic effects, or both, and there was a trend toward increased cardiac index and reduced preload values. On study day 10, the acute effects of candoxatril were similar to those on day 1 (i.e., ANP was further increased, aldosterone was suppressed, and right and left ventricular filling pressures were decreased). Thus, candoxatril may offer a new and effective therapeutic approach in the treatment of heart failure.
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PMID:Effectiveness of endopeptidase inhibition (candoxatril) in congestive heart failure. 138 91

The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.
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PMID:Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise. 139 15

The cardiac interstitium is composed of non-myocyte cells and a structural fibrillar protein network which plays a dominant role in governing the structure, architecture, and mechanical behaviour of the myocardium. Herein we review the fibrillar collagen network, its various components, and the functions they serve in the normal and structurally remodelled myocardium in arterial hypertension. The heterogeneity in myocardial structure, created by the altered behaviour of non-myocyte cells, particularly cardiac fibroblasts, which are responsible for collagen synthesis or degradation and thereby fibrous tissue accumulation, is a major determinant for the appearance of diastolic dysfunction and ultimately systolic myocardial failure. Regulatory mechanisms related to this fibrous tissue response are reviewed to draw attention to the hitherto neglected role of cardiac fibroblasts in mediating adverse structural remodelling of the myocardium and showing how this can be prevented through the use of pharmacological agents that interfere with the regulation of the myocardial collagen matrix. Several lines of evidence suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodelling of the non-myocyte compartment. These include the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition and aldosterone receptor antagonism that were found to prevent myocardial fibrosis in the rat with renovascular hypertension. In the rat with genetic hypertension, established left ventricular hypertrophy and abnormal myocardial diastolic stiffness due to interstitial fibrosis, RAAS inhibition resulted in restoration of myocardial structure and function to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial collagen matrix remodelling in arterial hypertension. 139 56

Studies over the past 10 years suggest that the atrial natriuretic factor (ANF) plays an important role in salt and water homeostasis. Responding to atrial stretch, the atria releases ANF into the circulation. The several actions of this hormone tend to increase renal NaCl excretion resulting in reduced blood volume and blood pressure. ANF increases the glomerular filtration rate and reduces sodium chloride reabsorption in the distal nephron. It also inhibits secretion of aldosterone from the adrenal cortex. Therefore actions of ANF appear to be opposed to the renin-angiotensin-aldosterone system. Drugs that alter ANF metabolism may constitute a new mechanism of treatment for hypertension and heart failure.
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PMID:Role of atrial natriuretic factor in salt and water homeostasis. 140 80

Urinary excretion of albumin and beta 2-microglobulin were measured in 13 patients with congestive heart failure, NYHA class II-IV, before and after captopril treatment for 4 weeks, and in 13 healthy control subjects. The urinary excretion of albumin was enhanced in heart failure patients compared to control subjects (12.0 micrograms min-1 vs 2.8 micrograms min-1; medians, p less than 0.01), whereas beta 2-microglobulin excretion was normal. No significant change in urinary excretion of albumin was observed after captopril. Using Spearmann's test the urinary excretion of albumin was correlated to the NYHA class (Px = 0.681, p less than 0.05, plasma renin (Px = 0.886, p less than 0.01) and plasma angiotensin II (Px = 0.5840, p less than 0.05). Correlations with atrial natriuretic peptide (rho = 0.412, p = 0.153) and aldosterone (Px = 0.487, p = 0.106) did not reach significance. By multiple linear regression analysis only plasma renin activity was correlated to albumin excretion. In conclusion, patients with congestive heart failure had an increased urinary excretion of albumin. It is suggested that the enhanced transglomerular passage of albumin in congestive heart failure is partly due to an increased intra-renal angiotensin II generation, but elevated plasma level of atrial natriuretic peptide and increased renal venous pressure may also be important pathogenetic factors.
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PMID:Enhanced urinary excretion of albumin in congestive heart failure: effect of ACE-inhibition. 141 Dec 51

Overall 210 patients aged 60-74 years suffering from coronary heart disease associated with chronic circulatory failure, stages I, IIA and IIB, 53 patients aged 45-59 years and 20 healthy persons aged 45-74 years were examined for the renin-angiotensin-aldosterone system and antidiuretic hormone. Renin activity, the concentration of aldosterone and vasopressin in blood plasma were investigated by radioimmunoassay. In the initial stage of heart failure, the elderly persons showed up more marked renin activation in blood plasma, followed by its lowering as decompensation progressed as well as an increase in the concentration of aldosterone and vasopressin, which resulted in the progress of circulatory failure.
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PMID:[The renin-angiotensin-aldosterone system and antidiuretic hormone in chronic circulatory failure in elderly subjects]. 144 Feb 54

To assess the feasibility of introducing captopril in patients with chronic heart failure on an outpatient rather than an inpatient basis a double-blind placebo-controlled study was carried out to compare either 6.25 mg or 25.0 mg of captopril as a starting dose; followed by either incremental doses of 6.25, 12.5, and 25.0 mg (low dose group), or 25.0 mg 8 hourly (high dose group) respectively. Forty-one patients in a general medical ward within a large teaching hospital with moderate to severe, stable, diuretic-controlled chronic heart failure, who were not hyponatraemic, hypokalaemic or on a dose of diuretic greater than 120 mg of frusemide took part. No patient experienced symptomatic hypotension. Both doses of captopril produced a significant drop in blood pressure (BP), the magnitude of which was similar in both groups. The first dose-induced fall correlated significantly with subsequent dose-related reductions in BP. Therefore if a patient did not have a hypotensive response to the first dose of captopril he/she would be unlikely to have one with subsequent doses. In the group as a whole, the magnitude of the fall in BP after the first dose correlated significantly with starting plasma levels of angiotensin II, atrial natriuretic peptide (ANP), aldosterone, and renin. However, on an individual basis, the two patients with the greatest fall in blood pressure did not have the most activated renin-angiotensin-aldosterone (RAA) system. This serves to emphasise the unpredictability of this response and the need to initiate therapy under clinical observation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Practical issues when initiating captopril therapy in chronic heart failure. What is the appropriate dose and how long should patients be observed? 146 41


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