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

Previous studies have demonstrated competition between sympathetic alpha receptor-mediated coronary vasoconstriction and local metabolic vasodilation during sympathetic activation. The present study tested if this competition also occurs in the presence of coronary stenosis. In closed-chest dogs, the left coronary artery was cannulated, and blood flow from the aorta was restricted by a moderate stenosis (70% area reduction). Intracoronary norepinephrine infusion produced coronary vascular alpha receptor and myocardial beta receptor activation. Norepinephrine infusion was repeated following alpha receptor blockade with phenoxybenzamine (0.25 mg/kg, injected into the coronary artery). Myocardial oxygen and lactate extraction, coronary sinus blood oxygen tension, and coronary resistance were compared at equal levels of myocardial oxygen consumption before and after coronary alpha receptor blockade. In the presence of coronary stenosis, intracoronary norepinephrine infusion decreased coronary sinus oxygen content and increased myocardial oxygen extraction. At comparable myocardial oxygen consumptions coronary vascular resistance was greater with alpha receptors intact than after alpha receptor blockade. The increase in myocardial oxygen extraction was prevented by alpha receptor blockade. We conclude that a sympathetic alpha receptor-mediated coronary vasoconstrictor influence operates, even in the presence of coronary stenosis, to limit oxygen delivery to the heart and increase myocardial oxygen extraction up to the point of cardiac failure, but that this vasoconstrictor effect does not result in net myocardial lactate production.
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PMID:Adrenergic coronary vasoconstriction in the presence of coronary stenosis in the dog. 746 Feb 14

Pulmonary hypertension in congestive heart failure causes medial hypertrophy in pulmonary vessels and thickening of the endothelial basement membrane. In this study, the functional consequences of such pulmonary vascular adaptations were evaluated. Heart failure was induced in dogs by rapid ventricular pacing (240 beats per minute) for 28 days, at which time left ventricular shortening fraction was decreased by 57% compared with that at baseline. Lung lobes from paced (n = 56) and control dogs (n = 68) were isolated and perfused with autologous blood. Total, arterial (Ra), and venous (Rv) vascular resistances were significantly increased and vascular capacitance decreased in lobes from paced animals compared with controls. Increments in Ra and Rv after intra-arterial boluses of norepinephrine were measured before and after sequential addition of the alpha 1- and alpha 2-receptor antagonists prazosin (16 mumol/L) and yohimbine (0.1 mumol/L) in the presence or absence of propranolol (5 mumol/L). Norepinephrine (1 to 40 micrograms) had little effect on Ra in the absence of propranolol, a pattern that persisted in control lobes after propranolol. However, when lobes from paced animals were pretreated with propranolol, norepinephrine increased Ra, Rv was increased after norepinephrine in control lobes, an effect that was enhanced in the paced group. In both groups, the increment in Rv was greater after propranolol. Irrespective of propranolol pretreatment, prazosin significantly attenuated, if not abolished, the response to norepinephrine. The enhancement in venous vascular reactivity in lobes from paced animals remained when venous pressure was elevated to 20 cm H2O. In control lobes under conditions of elevated tone or when endothelium-dependent relaxing factor was blocked, responses to norepinephrine did not mimic those observed in the paced group. Microvascular permeability, as measured by the capillary filtration coefficient, was not altered in the paced group. We conclude that the pulmonary adaptations to 4 weeks of rapid ventricular pacing include functional changes in pulmonary hemodynamics and vascular reactivity but not in microvascular permeability.
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PMID:Altered pulmonary microvascular reactivity to norepinephrine in canine pacing-induced heart failure. 751 65

1. Heart rate variability can be used to evaluate autonomic balance, but it is unclear how inotropic therapy may affect the findings. The aim of the study was to assess whether heart rate variability can differentiate between sympathetic stimulation induced by inotrope infusion or by physical exercise. 2. Ten patients with chronic heart failure (64.3 +/- 5.4 years of age) underwent four dobutamine infusions (8-min steps of 5 micrograms min-1 kg-1) and four supine bicycle exercise tests (5-min steps of 25 W). Plasma noradrenaline was evaluated, as well as the SD of R-R intervals, together with low-frequency (0.03-0.14 Hz) and high-frequency (0.15-0.4 Hz) components of heart rate variability using autoregressive spectral analysis. 3. Exercise and inotrope infusion produced similar changes in heart rate variability. An exercise load of 50 W and a dobutamine infusion of 15 micrograms min-1 kg-1 gave the following results respectively: heart rate, 120.3 +/- 3.0 beats/min versus 110.2 +/- 3.0 beats/min; SD, 16.0 +/- 1.1 ms versus 16.3 +/- 2.5 ms; low-frequency component, 4.3 +/- 0.3 ln-ms2 versus 4.4 +/- 0.3 ln-ms2 and high-frequency component, 2.6 +/- 0.3 ln-ms2 versus 2.2 +/- 0.3 ln-ms2. All comparisons were nonsignificant. The variables of heart rate variability showed high reproducibility in the same subject during different conditions. Noradrenaline was elevated by exercise from 326.0 +/- 35.2 pg/ml to 860.1 +/- 180.4 pg/ml (P < 0.05), but was unchanged by dobutamine infusion. 4. Heart rate variability changes cannot differentiate between dobutamine infusions and physical exercise, indicating that we should be cautious in evaluating patients undergoing inotropic therapy. The degree of receptor stimulations, rather than the level of sympathetic drive, would appear to determine the changes in heart rate variability.
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PMID:Sympathetic stimulations by exercise-stress testing and by dobutamine infusion induce similar changes in heart rate variability in patients with chronic heart failure. 755 56

Neurohormonal activation may provide a pathophysiological link between acute myocardial infarction and chronic congestive heart failure, and modulation of neurohormonal activity may be an important therapeutic target in these conditions. Plasma neurohormones were studied in 55 patients with acute myocardial infarction. Angiotensin II, noradrenaline and ANP were elevated in the early phase but tended to normalize during the first week in patients without signs of heart failure. In patients with heart failure angiotensin II and noradrenaline remained elevated for 1 month and ANP for 4-6 months. During head-up tilt, angiotensin II and noradrenaline increased most in patients with heart failure. In patients with a first myocardial infarction there was a positive correlation between sustained neurohormonal activity and infarct size. Almost complete suppression of plasma ACE activity was achieved within 30 min in 48 patients treated with intravenous enalaprilat, initiated within 24 h from the onset of infarction. The drug was tolerated in dosages of 1.0-1.2 mg given over 1-2h. Patients with systolic blood pressure between 100 and 110 mmHg incurred a greater risk of hypotension than those with higher blood pressure at baseline. Tolerance was not worse among patients treated with intravenous diuretics, metoprolol or nitroglycerin. A total of 98 patients were randomized to treatment with enalapril or placebo, initiated within 24 h from onset of infarction and continued for 4-6 months. During treatment there were no significant differences in plasma levels of angiotensin II, aldosterone, ANP or catecholamines between groups. Echocardiographic recordings were performed in 28 patients. Among patients on placebo there was a positive correlation between plasma levels of noradrenaline at days 5-7 and the increase in left ventricular volumes during the study period, and an inverse correlation between plasma aldosterone at days 5-7 and the increase in left ventricular ejection fraction during the study. No such correlation was found among patients on enalapril. ANP levels at 1 month correlated inversely with the left ventricular ejection fraction at the same time. Plasma neurohormones were measured in 223 patients with mild or moderately severe chronic heart failure, randomized to treatment with ramipril or placebo for 3 months. There was wide variation in hormone levels. Noradrenaline and aldosterone correlated inversely with exercise duration at baseline. Noradrenaline correlated positively with the degree of symptoms. Aldosterone and ANP were reduced with ramipril compared with placebo. Noradrenaline was reduced among patients with baseline levels in the highest tertile. Plasma hormones were also measured at peak exercise in 54 patients. Hormonal levels at rest correlated strongly with those at peak exercise.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurohormonal activation in patients with acute myocardial infarction or chronic congestive heart failure. With special reference to treatment with angiotensin converting enzyme inhibitors. 759 49

The understanding of the pathophysiology of heart failure is an emerging science. Although the mortality rate remains high, there has been some improvement in treatment in recent years. What was once thought to be a purely hemodynamic disorder now is understood to be a disease of cellular pathophysiology. The progression of compensated ventricular dysfunction to symptomatic heart failure is marked by the activation of vasoconstrictor hormones. Norepinephrine, renin-angiotensin-aldosterone, and arginine vasopressin are secreted in response to inadequate systemic perfusion. These combine to increase preload and afterload on an already failing heart. Baroreceptor function is attenuated, allowing for the continued sympathoexecitatory state. In addition, local tissue factors mitigate against a return to normal ventricular function by down-regulation of beta receptors, stimulation of local vasoconstrictor hormone secretion, and promotion of growth. Patients in intensive care units with chronic heart failure are best managed with an understanding of how their altered physiology affects their clinical presentation.
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PMID:Pathophysiology of heart failure: neuroendocrine response. 771 45

To determine if exercise intolerance and fatigue in chronic heart failure could be exacerbated by an abnormal metabolic response to exercise, we studied 12 patients with stable chronic heart failure and 12 normal volunteers during symptom-limited maximal treadmill exercise. Peak VO2 was 17.2 (15.1-19.2) ml.kg-1 x min-1 in patients and 29.9 (26.3-33.5) in controls (mean and 95% confidence intervals; P < 0.0001, t-test). Overall, levels in peripheral venous blood of glucose, glycerol and free fatty acids were greater in patients, although the differences became less marked with increasing exercise intensity. Noradrenaline was elevated in patients at rest, but the peak exercise response was similar to controls. Responses of adrenaline, insulin and glucagon were similar in both groups. We conclude that depletion of the levels of circulating substrates is not contributory to exercise intolerance and fatigue in chronic heart failure. Greater levels of glycerol and free fatty acids may be mediated by excess sympathetic nervous system activity, reflected in elevated noradrenaline levels.
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PMID:Metabolic responses to graded exercise in chronic heart failure. 829 29

The relationship between atrial natriuretic peptide (ANP) and peripheral sympathetic nervous system function was studied in diabetic and hypertensive rats. Animals were studied in diabetic and hypertensive rats. Animals were divided into four groups: control, diabetic, hypertensive and diabetic plus hypertensive. Diabetes was induced by streptozotocin (65 mg/kg) injection and hypertension by abdominal aortic constriction. Studies were performed at 1 and 6 weeks. Plasma ANP was increased at 1 week in all groups except controls. Noradrenaline turnover, an index of sympathetic activity in kidney, was attenuated in all pathological groups unlike controls. These changes were associated with increased activity of Ca2++Mg2+ ATPase, which is known to serve as a Ca2+ pump in kidney cortex basolateral membrane. In contrast, at 6 weeks, Ca2++Mg2+ ATPase was significantly decreased only in the diabetic plus hypertensive group which also showed signs of congestive heart failure, increased sympathetic activity and decreased plasma ANP levels. Intracerebral microdialysis of the extracellular space around the paraventricular nucleus (PVN) of the hypothalamus showed a decreased concentration of ANP in the diabetic plus hypertensive group. Infusion of ANP and pentolinium, a ganglionic blocker in diabetic plus hypertensive Ca2+ restored pump activity towards control values; ANP alone had no effect. Our results indicate decreased plasma ANP levels, increased sympathetic drive and a depressed kidney Ca2+ pump in diabetic plus hypertensive rats with heart failure. The relationships between these factors, and the potential modulating role of ANP is discussed.
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PMID:Observations on atrial natriuretic peptide, sympathetic activity and renal Ca2+ pump in diabetic and hypertensive rats. 839 86

In summary, ANP exerts its action in the kidney directly and indirectly. Its qualitative importance in body fluid regulation remains unsettled. It appears that its role is more important in pathophysiological conditions such as CHF in which plasma ANP is elevated. Paradoxically, kidneys in heart failure, nephrosis and diabetes are characterized by diminished responsiveness to exogenous ANP. Further studies are needed to ascertain whether this involves an alteration at the receptor or postreceptor site. The cellular mechanisms for receptor regulation and postreceptor signalling in physiology and pathophysiology need further investigation. Finally, a paracrine mode for the action of ANP and other natriuretic peptides has been proposed. Whether they act locally to facilitate sodium excretion and how much importance they have compared to circulating ANP remain to be clarified. The potential role of ANP as a growth inhibitor is also intriguing.
Nephron 1993
PMID:Biological significance of atrial natriuretic peptide in the kidney. 844 32

To study the physiological effect of the overexpression of myocardial Gsalpha (protein levels increased by approximately threefold in transgenic mice), we examined the responsiveness to sympathomimetic amines by echocardiography (9 MHz) in five transgenic mice and five control mice (both 10.3 +/- 0.2 months old). Myocardial contractility in transgenic mice, as assessed by left ventricular (LV) fractional shortening (LVFS) and LV ejection fraction (LVEF) was not different from that of control mice at baseline (LVFS, 40 +/- 3% versus 36 +/- 2%; LVEF, 78 +/- 3% versus 74 +/- 3%). LVFS and LVEF values in transgenic mice during isoproterenol (ISO, 0.02 micrograms/kg per minute) infusion were higher than the values in control mice (LVFS, 68 +/- 4% versus 48 +/- 3%; LVEF, 96 +/- 1% versus 86 +/- 3%; P < .05). Norepinephrine (NE, 0.2 micrograms/kg per minute) infusion also increased LVFS and LVEF in transgenic mice more than in control mice (LVFS, 59 +/- 4% versus 47 +/- 3%; LVEF, 93 +/- 2% versus 85 +/- 3%; P < .05). Heart rates of transgenic mice were higher than those of control mice during ISO and NE infusion. In three transgenic mice with heart rates held constant, LV dP/dt rose by 33 +/- 2% with ISO (0.02 micrograms/kg per minute) and by only 13 +/- 2% in three wild-type control mice (P < .01). NE (0.1 micrograms/kg per minute) also induced a greater effect on LV dP/dt in the three transgenic mice with heart rates held constant compared with three wild-type control mice (65 +/ 8% versus 28 +/- 4%, P < .05). Pathological and histological analyses of older transgenic mouse hearts (16.0 +/- 0.8 months old) revealed hypertrophy, degeneration, atrophy of cells, and replacement fibrosis reflected by significant increases in collagen volume in the subendocardium (5.2 +/- 1.4% versus 1.2 +/- 0.3%, P < .05) and in the cross-sectional area of myocytes (298 +/- 29 versus 187 +/- 12 micron2, P < .05) compared with control mouse hearts. These results suggest that Gsalpha overexpression enhances the efficacy of the beta-adrenergic receptor-Gs-adenylyl cyclase signaling pathway. This in turn leads to augmented inotropic and chronotropic responses to endogenous sympathetic stimulation. This action over the life of the animal results in myocardial damage characterized by cellular degeneration, necrosis, and replacement fibrosis, with the remaining cells undergoing compensatory hypertrophy. As a model, this transgenic mouse offers new insights into the mechanisms of cardiomyopathy and heart failure and provides a new tool for their study.
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PMID:Adverse effects of chronic endogenous sympathetic drive induced by cardiac GS alpha overexpression. 863 8

Effects of prolonged noradrenaline infusion on the density of cardiac beta-adrenoceptors, phosphodiesterase (PDE) and adenylate cyclase (AC) activities, and the ability of NKH477, 6-(3-dimethylaminopropionyl) forskolin hydrochloride, to increase tension development and heart rate were studied in rat cardiac preparations. Noradrenaline infusion (400 micrograms/kg/hr, s.c.) for 7 days significantly decreased cardiac beta-adrenoceptor density (Bmax), whereas the binding affinity (Kd) of the ligand was unchanged. The basal cardiac PDE activity was increased in treated rats, whereas there was no difference in the basal cardiac AC activity between treated and untreated rats. Significant decreases in basal developed tension and heart rate were observed in the left and right atrial muscles from treated rats, respectively. The positive inotropic and chronotropic potencies of NKH477 were unaffected by noradrenaline infusion, whereas the positive inotropic potencies of isoproterenol and 3-isobutyl-1-methylxanthine were significantly reduced. Thus, NKH477 appears to be superior to beta-adrenoceptor agnosits or PDE inhibitors as a cardiotonic drug in the treatment of heart failure accompanied by beta-adrenoceptor downregulation.
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PMID:[Effectiveness of NKH477, a novel forskolin derivative, in rat cardiac preparations with desensitized beta-adrenoceptors]. 881 Apr 93


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