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

The human heart contains both beta 1-adrenoceptors and a considerable number of beta 2-adrenoceptors, both of which bring about positive inotropic and chronotropic effects of beta-adrenoceptor agonists in vitro and in vivo. In chronic heart failure, the decrease in beta-adrenoceptor function is related to the severity of the disease. However, both cardiac beta 1- and beta 2-adrenoceptors seem to be differentially affected depending on the type of heart failure and its aetiology. beta 1-adrenoceptor function decreases in all forms of chronic heart failure. beta 2-adrenoceptor function, on the other hand, decreases in mitral valve disease, tetralogy of Fallot and end-stage ischaemic cardiomyopathy, and seems to be unaltered (or only mildly uncoupled) in end-stage dilated cardiomyopathy, and possibly in aortic valve disease. Since the human heart has few spare beta-adrenoceptors and these decline with increasing degree of heart failure, beta-adrenoceptor agonists (but only non-selective full agonists) may be of therapeutic use only if the heart needs acute inotropic support; in long-term treatment they may be not effective, since tolerance develops. On the other hand, for long-term treatment selective beta 1-adrenoceptor antagonists may be beneficial since they protect the heart from the deleterious effects of chronic exposure to high (cardiac derived) noradrenaline and simultaneously may restore the previously reduced beta-adrenoceptor function.
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PMID:Pathophysiology of the beta-adrenoceptor system in chronic heart failure: consequences for treatment with agonists, partial agonists or antagonists? 168 17

Cardiac and peripheral vascular effects of enoximone were investigated in a placebo-controlled, crossover, double-blind trial in 10 healthy volunteers. Electromechanical systole (QS2c) revealed direct positive inotropic effects and venous occlusion plethysmography of the calf arterial blood flow before and 1, 2, 3, and 4 h following 3 mg/kg of enoximone orally. Norepinephrine (7-640 ng/min) dose-response curves of a superficial human hand vein were measured and enoximone and enoximone sulfoxide plasma concentrations determined at the same time points. Peak effects on all measures were observed at 1 h and coincided with peak plasma concentrations: QS2c shortened by 36 +/- 13 ms (mean +/- SD; p less than 0.01 compared to placebo); arterial blood flow increased from 2.10 +/- 0.58 to 4.32 +/- 1.26 ml/100 ml/min (mean +/- SD; p less than 0.01 compared to placebo); and norepinephrine dose-response curves shifted to the right (p less than 0.01 with 20-320 ng/min compared to baseline), i.e., to achieve the same vasoconstriction as before enoximone, a three to five times higher dose of norepinephrine was needed. In addition to its positive inotropic effects, enoximone exerts peripheral arterial dilation and diminishes the venous vasoconstriction induced by norepinephrine. The combination of these pharmacological properties could be responsible for the beneficial effects of enoximone in heart failure.
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PMID:The effects of oral enoximone on cardiac performance, calf arterial blood flow, and constrictor effects of norepinephrine infused into hand veins in humans. 170 Feb 3

Radiotracer methods were used to measure the rates of regional release of adrenaline and noradrenaline into plasma in man. This was done as a partial test of a theory of essential hypertension pathogenesis which envisages an important cotransmitter function for neuronally released adrenaline. In healthy resting men no release of adrenaline could be detected from the heart, lungs or liver. Adrenaline was released into the right renal vein but an adrenal medullary source is suspected. With the relatively limited activation of the cardiac sympathetic outflow which accompanied mental challenge and isometric exercise, cardiac adrenaline release remained undetectable. During supine bicycle exercise, which increased cardiac noradrenaline release 10-30 fold, to a mean value of 197 ng/min, cardiac adrenaline release averaged 2.36 ng/min. In two clinical conditions associated with persistently elevated plasma adrenaline concentrations, cardiac failure and adrenaline-secreting phaeochromocytoma, regional release of adrenaline was clearly evident. Thus, in normal man during exercise, and in patients with cardiac failure at rest, adrenaline is released from non-adrenal sources, and probably from sympathetic nerves. Whether neuronal adrenaline release of the degree found would be sufficient to facilitate noradrenaline release, augment sympathetically-mediated cardiovascular responses and contribute to the development of arterial hypertension remains to be tested.
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PMID:Is adrenaline released by sympathetic nerves in man? 182 56

Neuroendocrine activity was studied in 60 consecutive untreated patients with dyspnoea and a clinical suspicion of heart failure. On the basis of the so-called Boston clinical criteria the diagnosis of heart failure was regarded as unlikely in 26 patients, possible in 15 patients, and definite in 19 patients. These groups were studied before any drug treatment was started and were compared with a control group of 69 healthy individuals. Plasma atrial natriuretic peptide concentration was clearly raised in patients with definite heart failure and slightly raised in patients with possible heart failure. Plasma adrenaline concentration was somewhat raised in patients with definite or possible heart failure, whereas plasma noradrenaline concentration was raised only in patients with definite heart failure. Plasma renin activity was not increased in any of the patient groups and plasma aldosterone concentration was slightly increased only in patients with definite heart failure. In the total patient series there were significant correlations between plasma atrial natriuretic peptide concentration and markers of the severity of left ventricular dysfunction. There was some evidence of neuroendocrine activation in untreated heart failure: plasma concentrations of atrial natriuretic peptide and catecholamines were increased but the renin-angiotensin-aldosterone system showed little or no activation.
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PMID:Neuroendocrine activity in untreated heart failure. 182 71

We investigated the basis for impaired left ventricular function of hearts in which hypertrophy was produced by gradual pressure overload. We measured myoplasmic free calcium concentration ([Ca2+]i) with fura-2 and sarcomere shortening in single myocytes isolated from control hearts and hypertrophied failing hearts. Diastolic [Ca2+]i was normal, but [Ca2+]i at the peak of contraction was depressed in myocytes from failing hypertrophied hearts. Increasing drive rate from 0.20 Hz to 5.00 Hz increased both diastolic and peak [Ca2+]i. Norepinephrine (3 x 10(-6) M) increased diastolic [Ca2+]i in all cells and tended to normalize peak [Ca2+]i in myocytes from hypertrophied failing hearts during 5.00 Hz drive. Depressed peak [Ca2+]i in the hypertrophied cells was paralleled by significant decreases in both the velocity and percent of sarcomere shortening, which were measured in cells not loaded with fura-2. Sarcomere length was correlated with estimates of [Ca2+]i in intact cells and with controlled levels of [Ca2+] in chemically "skinned" myocytes. A plot of sarcomere length against [Ca2+] gave a single continuous relationship that spanned resting and peak values at all drive rates in both the control and hypertrophied myocytes. Thus heart failure in this model is reflected in impaired myocyte contraction, which is closely related to reduced levels of [Ca2+]i during systole rather than to depressed myofilament sensitivity to Ca2+.
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PMID:Depressed intracellular calcium transients and contraction in myocytes from hypertrophied and failing guinea pig hearts. 183

Cardiac and peripheral vascular effects of enoximone were investigated in a placebo-controlled, crossover, double-blind trial in 10 healthy volunteers. Electromechanical systole (QS2c) revealed direct positive inotropic effects and venous occlusion plethysmography of the calf arterial blood flow before and 1, 2, 3, and 4 h following 3 mg/kg of enoximone orally. Norepinephrine (7-640 ng/min) dose-response curves of a superficial human hand vein were measured, and enoximone and enoximone-sulfoxide plasma concentrations were determined at the same time points. Peak effects on all measurements were observed at 1 h and coincided with peak plasma concentrations: QS2c shortened by 36 +/- 13 ms (mean +/- SD; p less than 0.01 compared to placebo); arterial blood flow increased from 2.10 +/- 0.58 to 4.32 +/- 1.26 ml 100 ml-1 min-1 (mean +/- SD; p less than 0.01 compared to placebo); norepinephrine dose-response curves shifted to the right (p less than 0.01 with 20-320 ng/min compared to baseline), i.e., to achieve the same vasoconstriction as before enoximone a 3-to-5-times higher dose of norepinephrine was needed. In addition to its positive inotropic effects, enoximone exerts peripheral arterial dilation and diminishes the venous vasoconstriction induced by norepinephrine. The combination of these pharmacological properties could be responsible for the beneficial effects of enoximone in heart failure.
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PMID:[Effect of oral administration of enoximone on cardiac performance, arterial circulation at rest and on the vasoconstrictor effect of local noradrenaline infusions into the human hand vein]. 183 92

Continuous ambulatory measurement of pulmonary arterial pressure was used to investigate changes following right heart catheterisation in patients with chronic heart failure. Ten males, mean age 56 years, with chronic heart failure, underwent 24 hour pressure recording using a micromanometer tipped catheter with in vivo calibration and frequency modulated recording. Eight patients were taking diuretics and 3 vasodilators. Blood was drawn for catecholamines, plasma renin activity and atrial natriuretic peptide 1 hour before catheterisation (-1 h), at the time of catheterisation (0 h) and 1, 2, 3, 4 and 6 hours later and aldosterone, cortisol and growth hormone at -1, 0 and 6 hours. Analysis of variance was used to determine changes in pulmonary arterial pressure, heart rate and hormones from the time of catheterisation in lying, sitting and standing postures. There was no significant change in pulmonary arterial pressure or heart rate over the 12 hours following or 24 hours after catheterisation in any posture. In the majority of patients plasma noradrenaline, plasma renin activity, atrial natriuretic peptide, aldosterone and cortisol were elevated. There was no significant change in hormone levels during the 6 hours following catheterisation. These findings suggest that the effect of invasive haemodynamic monitoring and chronic medical therapy on central haemodynamics is minor, and that a delay between insertion of catheters and measurement of pressure is unnecessary.
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PMID:The influence of right heart catheterisation on pulmonary arterial pressure in chronic heart failure: relationship to neuroendocrinal changes. 183 9

The hemodynamics of 18 patients (subgroup A) with severe heart failure (baseline Cl less than or equal to 1.55 l.min-1.m-2), including three patients with cardiogenic shock, and another 22 patients (subgroup B) with moderate heart failure (baseline Cl from 1.55 to 2.5 l.min-1.m-2) were investigated during a 24 h milrinone infusion, combined with investigation of the response of the sympathetic tone (plasma catecholamine levels) and the renin-angiotensin-aldosterone system to the hemodynamic improvement in both subgroups. Cl increased (p less than or equal to 0.001) to 162.7% after 5 min and further to 206.4% of baseline after 30 min of milrinone therapy in subgroup A, and in B to 139.3% and further to 146.4% after 15 min. PCWP decreased (p less than or equal to 0.001) to 83.8% and further to 65.5% of baseline after 30 min in subgroup A, and to 58.4% in subgroup B. Heart rate decreased (p less than or equal to 0.05) from 99.4 to 94.7 bpm in A and showed a decreasing tendency in B. MAP rose in A from 75.5 to 79.4 after 1 h and further to 83.3 mm Hg (p less than or equal to 0.01) after 24 h; in subgroup B, MAP did not change. Plasma noradrenaline level decreased (p less than or equal to 0.001) in A from 1419.5 (B: 782.9) to 838.2 (B: 529.6) after 1 h and further to 655.1 (B: 467.9) pg/ml after 24 h. Plasma renin decreased (p less than or equal to 0.01) in A from 1047.6 (B: 460.2) to 597.4 (B: 222.5) and further to 392.6 (B: 191.7) microU/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of hemodynamic changes in 24-hour milrinone infusion on sympathetic activity and the renin-angiotensin-aldosterone system in patients with severe heart failure]. 186 68

The acute central haemodynamic and neuroendocrine effects of intravenous flosequinan were studied in a group of 10 patients with severe heart failure. Flosequinan improved cardiac output by a maximum of 1.59 l.min-1, it reduced pulmonary capillary wedge pressure by 11.9 mm Hg and it also caused a reduction in right atrial pressure by a maximum of 7.2 mm Hg. It tended to cause a fall in plasma adrenaline levels but not in plasma noradrenaline. There was little fall in blood pressure in response to flosequinan and no patient developed an adverse event. Intravenous flosequinan may be a useful candidate drug for controlled clinical studies in patients with severe heart failure.
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PMID:The central haemodynamic effects of a single intravenous dose of flosequinan in patients with severe heart failure. 188 31

Kinetics of [3H]noradrenaline in the plasma were compared with plasma noradrenaline concentration in assessing overall sympathetic activity in six groups totalling 118 subjects. Arterial plasma noradrenaline in 21 control subjects was 204 +/- 14 pg/ml, similar to 20 patients with stable angina not treated with beta-blockers (194 +/- 25 pg/ml) and to 31 patients with stable angina treated with beta-blockers (232 +/- 19 pg/ml). Plasma noradrenaline was increased in 17 patients with unstable angina (366 +/- 50 pg/ml, P less than 0.01), in 14 patients with recent acute myocardial infarction (460 +/- 44 pg/ml, P less than 0.001) and in 15 patients with treated cardiac failure (582 +/- 78 pg/ml, P less than 0.001). Whole body clearance of noradrenaline from plasma was, however, reduced in each of the last three groups compared to controls by 20% (P less than 0.05), by 34% (P less than 0.01) and by 31% (P less than 0.01), respectively. In the 31 patients with stable angina on beta-blockers, clearance of noradrenaline was also reduced by 20% (P less than 0.05). Whole body noradrenaline spillover, a potentially more accurate measure of overall sympathetic activity than concentration of noradrenaline in plasma, was 235 +/- 20 ng min-1 m-2 in controls, was similar in subjects with stable angina (no beta-blockers; 260 +/- 34 ng min-1 m-2, beta-blockers; 200 +/- 17 ng min-1 m-2), but was increased in patients with unstable angina (310 +/- 27 ng min-1 m-2, P less than 0.05), with recent acute myocardial infarction (346 +/- 40 ng min-1 m-2, P less than 0.05) or with heart failure (438 +/- 65 ng min-1 m-2, P less than 0.01). Overall sympathetic activity is unchanged in stable angina, but is progressively increased in patients with unstable angina, recent myocardial infarction or heart failure. Plasma concentration of noradrenaline fails accurately to reflect this as a result of decreased clearance of noradrenaline in these patients. The results show the potential limitations of measurement of noradrenaline in the plasma as an index of overall sympathetic activity and the importance of assessing clearance.
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PMID:Plasma noradrenaline as an index of sympathetic tone in coronary arterial disease: the confounding influence of clearance of noradrenaline. 196 93


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