Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is some evidence that exercise intolerance in chronic heart failure is linked to the activity of compensatory mechanisms, including neurohumoral factors. However, there is a lack of correlation between exercise capacity and the degree of LV-dysfunction in this setting. Impaired skeletal muscle perfusion during exercise appears to be involved in reduced exercise capacity in patients with heart failure. The peripheral vasoconstriction mediated by increased sympathetic tone and activated plasma renin-angiotensin-aldosterone system (RAAS) may act primarily for short-term control and its short-term inhibition does not restore exercise capacity. The effects of the vascular RAS, impaired flow-dependent endothelium-mediated dilation (e.g. due to chronically reduced flow) and structural alterations of the vessel wall only slowly emerge over time. In addition, fluid retention may contribute to increased vascular stiffness in chronic heart failure. Improved cardiac output with acute administration of vasodilators and inotropes is not immediately translated into increased flow to skeletal muscle, because (1) the reversal of the above delineated peripheral alterations develops slowly over time; such agents given acutely may cause redistribution of blood flow in skeletal muscle without improving oxygen availability, (2) intrinsic abnormalities of skeletal muscle exist in chronic heart failure; e.g. due to chronic deconditioning, resulting in reduced oxidative capacity of skeletal muscle, as suggested by ultrastructural analysis and NMR-spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Reduced exercise tolerance in chronic heart failure and its relationship to neurohumoral factors. 168 Jun 84

The aim of this study was to investigate the role of the renin-angiotensin-aldosterone system during anti-heart failure treatment with additional enalapril versus conventional vasodilator therapy (hydralazine + sorbitrate) and to assess whether or not enalapril can be suggested as the preferential vasodilator therapy in patients with chronic congestive heart failure. Over a 2.5-year period, 120 patients (New York Heart Association II-IV, creatinine less than or equal to 2.0 mg/dl) were enrolled in the study and randomly assigned to receive enalapril or hydralazine and sorbitrate therapy in addition to optimal digitalis and diuretics administration. At the end of a one-year followup, there was a tendency for mortality to be lower in the enalapril[correction of enlapril] group (4 cases) compared to the conventional group (9 cases), but the difference was not significant (p = 0.21). Both groups showed similar increases in plasma renin activity. The plasma aldosterone level decreased significantly in the enalapril group (p less than 0.005); whereas it rose significantly in the conventional group (p less than 0.005). The plasma norepinephrine level of the enalapril group fell significantly when compared with the conventional group. Thus, enalapril therapy achieved better reduction in the activating sympathetic system (p less than 0.0001). Reduction in the anti-diuretic hormone level was also found to be highly significant in the enalapril group, whereas no difference was seen in the conventional group. Furthermore, the serum creatinine level and blood urea nitrogen remained unchanged in the conventional group; whereas both were demonstrated to be reduced significantly in the enalapril group at a 1-year follow up.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison of enalapril and conventional vasodilator therapy in patients with chronic congestive heart failure. 168 Sep 82

Previous studies have indicated that patients with an acute myocardial infarction have marked activation of all neurohumoral systems on admission to the hospital. This activation begins to subside within the first 72 hours so that by 7-10 days, all plasma neurohormones have returned to normal. The only documented exceptions were found to occur in patients with left ventricular dysfunction and overt heart failure, where both plasma renin activity and atrial natriuretic peptide were increased, and in patients with left ventricular dysfunction but no overt heart failure, where only atrial natriuretic peptide was increased. Although these studies suggest that neurohumoral activation rarely occurs at the time of hospital discharge, they were small and may have missed an important subgroup of patients with persistent neurohumoral activation. In the Survival and Ventricular Enlargement (SAVE) study, 522 patients had plasma neurohumoral levels measured at a mean of 12 days postinfarction. All SAVE patients had left ventricular dysfunction (left ventricular ejection fraction less than or equal to 40%), but no overt heart failure. In this group of patients, all neurohumoral levels (plasma renin activity, norepinephrine, arginine vasopressin, and atrial natriuretic peptide) were found to be increased compared with age-matched control subjects. These results indicate that, in fact, a subgroup of patients without overt heart failure has persistent neurohumoral activation at the time of hospital discharge postinfarction, and that this activation involves several neurohumoral systems. Since patients with persistent neurohumoral activation postinfarction are likely those most at risk of developing complications and the ones most likely to benefit from pharmacologic interventions blunting the effects of neurohumoral activation, measurement of predischarge neurohumoral levels may be useful.
 ...
PMID:Activation of neurohumoral systems following acute myocardial infarction. 168 82

Ibopamine (IP) is a novel dopamine analogue for which beneficial effects have been shown in chronic heart failure. Hemodynamic effects of the substance include an increase in cardiac output and a decrease in the peripheral resistance. Aside from these hemodynamic effects, changes in renal (increased diuresis) and neurohumoral parameters (decreased plasma renin activity, aldosterone, norepinephrine, increased ANF and cGMP) have been found. The renal effects may originate from three independent mechanisms: 1) direct impact of improved hemodynamic parameters on the renal perfusion; 2) the improved cardiac performance results in a reduction of compensatory hormonal adaptations, such as the activation of the renin-angiotensin-aldosterone-axis or the sympathetic system; 3) direct effects on the intrarenal hemodynamic and glomerular/tubular functions induced by stimulation of renal dopaminergic receptors. The continued decrease of the plasma renin activity by 35% results in a reduction of the plasma levels of angiotensin II and aldosterone. Additionally, an increase in plasma atrial natriuretic factor (ANF) and its second messenger cyclic guanosine monophosphate (cGMP) was observed after ibopamine, which could contribute to the diuretic action of the drug. These findings underline the importance of extrarenal effects of a drug in the treatment of heart failure, this may essentially contribute to the improvement of cardiac performance, independent of positive inotropy.
 ...
PMID:[Ibopamine--acute hemodynamic, renal and neurohumoral effects]. 168 94

The acute systemic and regional hemodynamic responses to a single oral dose (4 mg) of the angiotensin converting enzyme inhibitor perindopril were investigated in 10 patients with severe congestive heart failure. Perindopril produced significant and long-lasting decreases in systemic vascular resistance (-18%), right atrial pressure (-60%), and mean pulmonary capillary wedge pressure (-28%), whereas it significantly increased cardiac index (+ 12%). Brachial (+ 130%, pulsed Doppler technique) and renal (+ 34%) blood flows were also significantly increased whereas hepatic blood flow remained unchanged. Brachial flow/cardiac output and renal flow/cardiac output ratios increased significantly from 0.8 to 1.6 and from 13.2 to 16.5, respectively. The maximal decreases in forearm and renal (but not in systemic) vascular resistances were correlated with the basal plasma norepinephrine concentrations but not plasma epinephrine concentrations or plasma renin activity. We conclude that in severe heart failure (a) perindopril considerably improves systemic hemodynamics and exerts an inhomogeneous vasodilating effect, resulting in a redistribution of flows toward the forearm and renal territories, (b) norepinephrine is a major determinant of the arteriolar tone in these two vascular beds, and (c) the pulsed Doppler is a particularly suitable method to non-invasively detect and assess hemodynamic improvements in heart failure patients.
 ...
PMID:Systemic and regional hemodynamic effects of perindopril in congestive heart failure. 169 80

It has been hypothesized that a decreased activity of vagal afferents might contribute to the activation of neurohumoral systems in congestive heart failure. Therefore, we studied the effects of vagal nerve blockade by local anesthesia on neurohormones in six conscious dogs before and after induction of heart failure by rapid right ventricular pacing (250 beats/min, 10 days). In healthy dogs, vagal blockade significantly increased plasma vasopressin levels (from 1.5 +/- .6 to 13.7 +/- 10.5 pg/ml, p less than 0.02), without significantly affecting plasma catecholamines and renin. After 10 days of pacing, mean arterial pressure and cardiac output were decreased, right atrial and pulmonary arterial pressures and plasma levels of norepinephrine, dopamine, and atrial natriuretic peptide were increased. In this state, vagal blockade significantly increased plasma renin activity (from 1.52 +/- .43 to 3.18 +/- .54 ngAI/ml/h, p less than 0.02) and plasma vasopressin (from 4.2 +/- 3.3 to 89.1 +/- 54.9 pg/ml, p less than 0.02), this increase being significantly higher than in healthy dogs. We conclude that in these dogs with low cardiac output state, which resembles early heart failure, vagal afferent activity is increased and effectively suppresses renin and vasopressin. This does not exclude the possibility that in later stages of heart failure vagal afferent dysfunction may develop, resulting in neurohumoral disinhibition.
 ...
PMID:Effects of vagal blockade on neurohumoral systems in conscious dogs with heart failure. 169 88

In order to assess potential harmful effects of the partial beta-1 agonist xamoterol during long-term therapy, we randomly assigned 30 patients with coronary arterial disease and heart failure in classes II and III of the classification of the New York Heart Association to 200 mg of xamoterol twice daily or placebo during a treatment period of 3 months. A supine bicycle exercise test was performed at baseline and after three months in order to assess changes of exercise capacity. Blood samples for determination of creatinine, electrolytes, renin and norepinephrine were withdrawn simultaneously. Twenty-four hour ambulatory Holter electrocardiograms were performed before study, at the end of the study and 72 hours after withdrawal of study medication. On xamoterol, exercise capacity increased from 21.9 +/- 9.7 to 27.8 +/- 14.8 kilojoule (P = 0.032) compared to baseline levels. Exercise duration increased from 340 +/- 115 to 400 +/- 144 seconds (P = 0.043). Heart rate decreased by 10% (P = 0.05) at the 50 watt level and by 10% (P = 0.024) on maximum exercise compared to the baseline values. The rate pressure product was unchanged at rest and dropped by 11% (P = 0.038) on maximum exercise. In contrast, on placebo no significant changes occurred. During xamoterol therapy no changes of blood pressure, electrolytes, renal function and the time-intervals of electrocardiogram were observed. Xamoterol did not enhance arrhythmias during 24-hour ambulatory Holter monitoring. No serious side effects were observed. Xamoterol would appear to be a suitable and safe drug in the therapy of mild to moderate heart failure.
 ...
PMID:Exercise capacity, arrhythmias, humoral and chemical parameters during long-term therapy with xamoterol. 169 69

Peak III phosphodiesterase (PDE) inhibitors have combined positive inotropic and vasodilator effects. We studied 10 patients with chronic heart failure during and after infusion of intravenous (i.v.) ICI 153,110, an investigational peak III PDE inhibitor. Maximum hemodynamic response for the group occurred after cessation of infusion at a lower plasma drug concentration. At maximum hemodynamic response, cardiac index (CI) increased (2.4 +/- 0.5 vs. 3.2 +/- 0.37 L/min/m2, p less than 0.05) with a decrease in mean arterial pressure (MAP 91 +/- 5 vs. 80 +/- 3 mm Hg, p less than 0.05), pulmonary capillary wedge pressure (PCWP 25 +/- 2 vs. 17 +/- 3.1 mm Hg, p less than 0.01), systemic vascular resistance (SVR 1,422 +/- 106 vs. 983 +/- 97 dynes.s.cm-5, p less than 0.05) and pulmonary vascular resistance (PVR 227 +/- 39 vs. 16 +/- 31 dynes.s.cm-5, p less than 0.05). During the infusion, plasma renin activity (PRA) decreased from 6.34 +/- 2.53 to 3.6 +/- 3 ng/ml/h (NS). The five patients with high baseline PRA had a significant decrease (11.2 +/- 2.5 vs. 5.4 +/- 1.67 ng/ml/h, p less than 0.01) that preceded changes in CI and SVR by 1-2 h. These data suggest that reduction in PRA may have contributed to the hemodynamic effects of this peak III PDE inhibitor.
 ...
PMID:Acute neurohormonal and hemodynamic response to a new peak III phosphodiesterase inhibitor (ICI 153,110) in patients with chronic heart failure. 170 Feb 5

To test the efficacy of exogenous prostaglandins for vasodilator therapy in heart failure, we studied the effects of the prostacyclin-derivative iloprost (1.5-150 ng/kg/min) in seven conscious dogs before and after induction of heart failure by right ventricular pacing (250/min. 10 days). In healthy dogs, iloprost (150 ng/kg/min) decreased mean arterial blood pressure (MAP) (-45%) by a decrease in total peripheral resistance (TPR) (-55%), and increased cardiac output (CO) (+24%) and heart rate (HR) (+20%) with no effect on right atrial and pulmonary arterial pressures (RAP, PAP). Plasma norepinephrine (NE) (+47%), renin (+351%), and aldosterone (+126%) were increased. Urine flow (-70%) and Na excretion (-53%) were decreased. Iloprost (15 ng/kg/min) increased renal blood flow (RBF) (+29%), but did not change glomerular filtration rate (GFR). In dogs with heart failure, iloprost decreased arterial BP (-31%), TPR (-42%) and pulmonary vascular resistance (-28%) and increased CO (+29%), with no change in RAP and PAP. Plasma NE (+34%), renin (+385%), and aldosterone (+146%) were increased. RBF was unchanged. GFR (-24%) and filtration fraction (FF) (-30%) were decreased, as was urine flow (-65%). In experimental heart failure, iloprost is a potent arteriolar dilator, increasing CO with no preload effect. These beneficial effects are limited, however, by further neurohumoral activation and deterioration of renal function.
 ...
PMID:Hemodynamic, hormonal, and renal effects of the prostacyclin analogue iloprost in conscious dogs with and without heart failure. 170 1

Previous physiological and biochemical studies suggest the existence of an endogenous renin-angiotensin system (RAS) in the kidney. However, these data cannot exclude the contribution of the circulating RAS. Proof of the local synthesis of RAS components in the kidney has been obtained recently through the use of molecular biological techniques. Using Northern blot analysis, we have demonstrated the intrarenal expression of renin, angiotensinogen, and angiotensin-converting enzyme messenger RNAs. Employing in situ hybridization histochemistry, we have localized the intrarenal tissue sites of renin and angiotensinogen messenger RNA synthesis. Renin gene expression was found in cells of the juxtaglomerular apparatus. Angiotensinogen mRNA was primarily produced in the proximal convoluted tubule with lesser amounts in glomerular tufts and vasculature. These findings led us to hypothesize that the proximal tubule is a major site of renal Ang II synthesis and that locally synthesized Ang II might directly modulate tubular function. Both genes are subject to feedback regulation. Our studies showed that Ang II exerted a stimulatory effect on angiotensinogen but a negative feedback effect on renin gene expression. Dietary NaCl restriction stimulated the expression of both genes, although the onset of renin gene activation required more prolonged sodium chloride restriction. Furthermore, our data indicated that the sodium cation, irrespective of the anion, was primarily important in regulating renal angiotensinogen mRNA levels. Our studies also showed altered intrarenal renin or angiotensinogen expressions in pathophysiological states, e.g. in experimental heart failure and the spontaneously hypertensive rat. Taken together, these data support the existence of a intrarenal RAS and suggest its potential roles in the regulation of renal function in health and disease.
 ...
PMID:Evolving concepts of the intrarenal renin-angiotensin system in health and disease: contributions of molecular biology. 170 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>