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)

We analyzed the effect of enalapril (0.1 mg/kg p.o. twice daily) on plasma electrolytes, urea, and creatinine in low cardiac output failure. In 14 male dogs implanted with chronic instrumentation, tachycardia was induced by ventricular pacing (265 impulses/min., 10-14 days). In 7 untreated dogs, pacing progressively lowered aortic flow by 44% and induced hyponatremia and elevations of plasma urea, creatinine, and potassium. Treatment with enalapril (n = 7) during pacing reduced the decrease in aortic flow by 33% and prevented changes in plasma urea, potassium, and sodium. We conclude that this is due to enalapril-induced retardation of heart failure progression.
Nephron 1990
PMID:Converting enzyme inhibition by enalapril in experimental heart failure. 234 93

The stimulant effects of adrenaline and noradrenaline on contractile force and adenylate cyclase, mediated through beta 1 and beta 2-adrenoceptors, are analysed in isolated atrial and ventricular myocardium of man. The tissues were obtained from patients without advanced heart failure undergoing heart surgery. Usually, both adrenaline and noradrenaline stimulated adenylate cyclase predominantly through ventricular and atrial beta 2-adrenoceptors. Because the relative density of beta 2-adrenoceptors is usually smaller than that of beta 1-adrenoceptors, stimulation of one beta 2-adrenoceptor leads to the production of up to 10 times more cyclic AMP molecules than does stimulation of one beta 1-adrenoceptor. Adrenaline and noradrenaline maximally enhance contractile force through both atrial and ventricular beta 1-adrenoceptors. Adrenaline can also maximally enhance contractile force through atrial beta 2-adrenoceptors. In the ventricle, adrenaline increases force via beta 2-adrenoceptors by up to 60% of its maximal beta 1 response. Noradrenaline can increase atrial and ventricular contractile force through beta 2-adrenoceptors but only at high concentrations. Unexpectedly, in atria from patients treated with the beta 1-selective antagonist atenolol, contractile responses to adrenaline are markedly and selectively augmented through activation of beta 2-adrenoceptors. In atria from atenolol-treated patients equi-inotropic concentrations of adrenaline and noradrenaline acting through beta 2 and beta 1-adrenoceptors, respectively, cause similar increases of cyclic AMP and of cyclic AMP-dependent protein kinase activity.
 ...
PMID:A comparison of the effects of adrenaline and noradrenaline on human heart: the role of beta 1- and beta 2-adrenoceptors in the stimulation of adenylate cyclase and contractile force. 257 19

To enable the assessment of a possible gradual loss of myocardial catecholamines in heart failure, we determined control values in endomyocardial biopsies from normal human right ventricular myocardium. The reproducibility of the determinations and its dependence on the reference system, wet weight (wwt) or non-collagen-protein (NCP), was investigated in explanted hearts. Parallel determinations of norepinephrine in several samples from 1-2 mg in the same heart yielded a variability of about 20%. To obtain reproducible values, catecholamine concentrations had to be related to non-collagen-protein. Non-collagen-protein content was higher in the ventricles (138 +/- 16 micrograms/mg wwt) than in the atria (102 +/- 15 micrograms/mg wwt). Norepinephrine levels in normal human myocardium, measured in right ventricular endomyocardial biopsies were 10.3 +/- 3 pg/micrograms NCP. If they were compared with norepinephrine levels in right atrial samples from 11 patients without heart failure, obtained at open heart surgery (17.6 +/- 6 pg/micrograms NCP), an atrioventricular gradient, with ventricular norepinephrine content being 58% of right atrial levels was calculated for healthy human hearts. This gradient was almost identical with that found in heart failure, patients, where right ventricular norepinephrine amounted to 60% of right atrial levels. This implicates a percentually homogeneous loss of norepinephrine in heart failure, which, however, does not equalize ventricular and atrial levels. Thus, to interpret myocardial catecholamine content in cardiac diseases, normal values in corresponding areas are mandatory.
 ...
PMID:[Myocardial catecholamine content in heart failure--II: Measurement in endomyocardial biopsies, reference systems, normal values]. 262 17

The past 15 years have been witness to a remarkable growth in knowledge regarding the modulation of "sympathetic traffic" to neuroeffector organs, including vascular tissue. The release of norepinephrine from peripheral sympathetic neurons is now known to be under both negative and positive feedback control. Norepinephrine, when released from peripheral neurons, acts on presynaptic alpha 2-receptors to inhibit further neurotransmission. Vascular postsynaptic alpha 2-receptors, sensitive to circulating catecholamines, subserve vasoconstriction. The antihypertensive agents clonidine, guanabenz and guanfacin likely reduce blood pressure by acting centrally on alpha 2 postsynaptic neurons to limit sympathetic transmission to blood vessels. Clonidine can produce venoconstriction and thereby improve orthostatic hypotension by activating venous alpha 2-receptors. Additional presynaptic dopaminergic receptors (DA2), muscarinic receptors (acetylcholine), opioid receptors, prostaglandin receptors, adenosine receptors (A1) and histamine (H2) receptors are present on sympathetic nerve membranes and, when engaged with the appropriate ligand, can limit the exocytotic process. Gamma-aminobutyric acid and serotonin demonstrate similar roles in reducing sympathetic nerve activity. In contrast to these inhibitory presynaptic mechanisms, facilitation of norepinephrine release appears to occur by way of neuronal angiotensin II receptor activation and perhaps through stimulation of sympathetic nerve membrane beta 2-receptors. An appreciation of these inhibitory and facilitator mechanisms is useful in the treatment of a variety of clinical conditions, including hypertension, heart failure, orthostatic hypotension, septic shock and a number of common withdrawal syndromes.
 ...
PMID:Modulation of peripheral sympathetic nerve transmission. 283 2

The renal and pulmonary hemodynamic effects of fenoldopam, dobutamine, dopamine and norepinephrine were compared in the pentobarbital-anesthetized dog. Animals were pretreated with propranolol (1 mg/kg, i.v.) to eliminate beta-adrenoceptor-mediated effects in the renal and pulmonary circulations. Heparinized blood was withdrawn from the right femoral artery and transferred, via a peristaltic pump, to the pulmonary arterial branch supplying the left diaphragmatic lobe of the lung. The flow rate of the pump was set so that the perfusion pressure in the lobe was equal to resting diastolic pulmonary artery blood pressure. Under these conditions of constant flow, changes in perfusion pressure reflect changes in pulmonary vascular resistance. Renal blood flow was measured in the same experiments via an electromagnetic flow probe which was placed directly on the left renal artery. Intraarterial administration of fenoldopam resulted in a marked reduction in renal vascular resistance at doses that had virtually no effect on pulmonary vascular resistance. Conversely, dobutamine increased pulmonary vascular resistance slightly, and had no effect on the renal circulation. Dopamine increased pulmonary vascular resistance at all doses, and exhibited a biphasic effect on renal vascular resistance. At low doses, dopamine produced a modest reduction in renal vascular resistance, and at higher doses, dopamine significantly increased renal vascular resistance. Norepinephrine increased both pulmonary and renal vascular resistance at all doses, as expected. These results indicate that fenoldopam may be hemodynamically favorable over dobutamine and dopamine in the management of patients with low output cardiac failure since fenoldopam improves renal hemodynamics at doses that have little or no effect on the pulmonary circulation.
 ...
PMID:Comparison of the renal and pulmonary hemodynamic effects of fenoldopam, dobutamine, dopamine and norepinephrine in the anesthetized dog. 289 93

This paper discusses the possible pathogenesis of the cerebral atrophy (CA) observed in a large percentage of uraemic patients, taking the form of prevalently cortical damage (cortical atrophy) and/or subcortical enlargement of ventricular cavities (subcortical atrophy). This central nervous system pathology seems to share very little either with the better known 'dialysis encephalopathy' or with the 'acute encephalopathy syndrome', even though sporadic cases of both these forms have shown concomitant CA. Histopathologically it offers the picture of loss of neurons and nerve fibres and can thus be compared with uraemic peripheral nervous system damage. CA is unquestionably important because of its implications in terms of impairment of superior cortical functions, just as in CA of non-uraemic aetiology. A first aetiopathogenic hypothesis might include endogenous uraemic intoxication to the nerve tissue, believed responsible for peripheral uraemic neuropathy, but other possibilities merit consideration: vascular calcification secondary to hyperparathyroidism, blood lipid disorders, and systemic hypertension--factors that contribute to impairing the brain vasculature, with cascade effects on brain tissue oxygenation, neuronal metabolism, and energy exchanges. Tissue oxygenation is already jeopardized in the uraemic patient by the concomitant chronic anaemia and by cardiac insufficiency in cases with hypertensive heart disease. In dialysis patients with volume-dependent hypertension the brain may be further damaged by abrupt pressure changes produced by dialytic ultrafiltration; these constitute a severe challenge to cerebral blood flow autoregulation. Cyclic variations of brain tissue hydration connected with regular dialysis treatment may have adverse effects on neurotransmitter functions, particularly those mediated by neuropeptidergic systems. Chronic intoxication may result from oral Al(OH)3 of phosphorus-chelating agents: in animal studies and clinical observations in non-uraemic populations the neurotoxic potential of Al is indicated by a significant correlation between histological neuronal damage, impaired function, and Al concentration in brain tissues. In addition, a concausal role of malnutrition in central nervous system damage in the uraemic patient cannot be overlooked, since malnutrition is known to give rise to functional and structural alterations in non-uraemic human pathology. In the light of these clinical observations and experimental findings, it would appear that the prevention of CA in uraemia is today feasible.
Nephron 1988
PMID:Pathogenesis of cerebral atrophy in uraemia. State of the art. 328 91

Serotonin (5-hydroxytryptamine) has multiple cardiovascular actions. The presence of serotonin in the heart suggests it may be an endogenous source of inotropic support during physiologic or pathologic stress. Serotonin may increase cardiac contractility by augmenting release of norepinephrine at sympathetic nerve endings. Norepinephrine release is markedly elevated in patients with heart failure. To explore the role of serotonin in enhancing norepinephrine release in patients with heart failure, ketanserin, a specific serotonin antagonist, was used as a physiologic tool to examine the effect on transmyocardial norepinephrine flux. Ketanserin (10 mg bolus, 4 mg/hr infusion for +/- 40 min) was administered intravenously to nine patients with congestive heart failure (NYHA III or IV) secondary to congestive cardiomyopathy (N = 7), or ischemic heart disease (N = 2). Plasma catecholamines (norepinephrine, epinephrine, dopamine) were measured in the aorta (Ao) and the coronary sinus (CS) of patients at rest and during supine leg exercise before and after administration of ketanserin. Baseline norepinephrine levels were markedly elevated at rest and during exercise in all patients. Norepinephrine levels were significantly higher in the CS than in the Ao (rest, CS 1185 +/- 235, Ao 878 +/- 381 pg/mL, P less than .05; exercise, CS 2239 +/- 697, Ao 1453 +/- 697 pg/mL, P less than .05). Baseline epinephrine levels were within normal limits. In contrast to norepinephrine levels, epinephrine levels were consistently higher in the Ao than in the CS, indicating unimpaired extraction or uptake across the heart. The relationship between norepinephrine and epinephrine concentration in the Ao and CS suggested a net overflow of norepinephrine in the CS.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of 5-hydroxytryptamine blockade with ketanserin on myocardial uptake of epinephrine and norepinephrine in patients with congestive heart failure. 368 May 95

The effects of sino-aortic denervation (SAD) on cardiac noradrenaline stores, turnover and neuronal re-uptake were examined in normotensive rabbits and rabbits with two-kidney, two wrapped hypertension. Ten to 12 days after SAD, left ventricular (LV) noradrenaline stores were reduced in renal hypertensives to 43% of that of the sham-operated rabbits, although there was no overt evidence of heart failure. This did not occur after SAD of normotensive rabbits. The reduction in noradrenaline content was accompanied by a reduction in [3H]-noradrenaline turnover time (4.4 h) compared with renal hypertensive (7.4 h) and the normotensive subgroups (9.3 h). Noradrenaline turnover rates were elevated by 25% in hypertensive compared with normotensive rabbits. Left ventricular tyrosine hydroxylase, dopamine-beta-hydroxylase and type A monoamine oxidase activities were similar in normotensive and hypertensive rabbits and were unaffected by SAD. Following SAD of hypertensive rabbits cardiac neuronal uptake for alpha-methylnoradrenaline was reduced by 33% compared with either the hypertensive or the normotensive rabbits. Sino-aortic denervation did not affect neuronal uptake in normotensives. These results suggest that following SAD of hypertensive rabbits, cardiac noradrenaline stores are depleted by enhanced cardiac sympathetic activity (reduction in [3H]-noradrenaline turnover time) and a reduction in neuronal re-uptake. It appears that the hypertensive hypertrophied heart is less able to tolerate chronic sympathetic overactivity and/or liability in coronary oxygen supply brought about by SAD.
 ...
PMID:Differential effects of sino-aortic denervations on cardiac noradrenaline stores, turnover and neuronal re-uptake in normotensive and renal hypertensive rabbits. 377 95

2 cases of acute renal failure associated with diclofenac therapy are reported. In the 1st case no other risk factors but diclofenac administration were identified. Renal biopsy showed patchy interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. In the 2nd case preexisting nephropathy and heart failure were underlying illnesses. In both cases renal function returned to the basal values after stopping the drug.
Nephron 1985
PMID:Diclofenac-associated acute renal failure. Report of 2 cases. 402 22

Controversy exists over the nature of the abnormality in cardiac sympathetic nerves in heart failure. In the cardiomyopathy of the Syrian hamster, reduction in tissue stores and increased turnover of norepinephrine is clearly associated with excessive sympathetic stimulation but in animal models and humans with heart failure secondary to mechanical overload there is evidence for depression of neuronal uptake. Because norepinephrine is both released and taken up by sympathetic fibers it is impossible to assess norepinephrine kinetics in an intact heart without separating these two functions. A technique for doing so has recently been developed in normal dogs and we therefore acquired similar data in humans with heart failure secondary to chronic pressure and volume overload. The technique involves the combination of transient norepinephrine tracer coronary sinus outflow in relation to intravascular and interstitial references after simultaneous injection into the left coronary artery and the measurement of endogenous norepinephrine concentrations in artery and coronary sinus. We found a marked reduction in cardiac norepinephrine release and uptake in a group of patients with clinical left ventricular failure secondary to mechanical overload, relative to a group of patients with no failure. Norepinephrine balance and overflow across the heart were not significantly different. We conclude that there is hypofunction of the cardiac sympathetic nerves in heart failure secondary to mechanical overload and that traditional methods are inadequate in assessing cardiac norepinephrine kinetics when there are simultaneous changes in neuronal uptake and release.
 ...
PMID:Tracer norepinephrine kinetics in coronary circulation of patients with heart failure secondary to chronic pressure and volume overload. 405 51


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