Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

Prenalterol (beta 1-agonist), denopamine (beta 1-agonist), and zinterol (beta 2-agonist) were partial agonists of adenylate cyclase (AC) stimulation in human ventricular myocardium obtained from nonfailing chambers whose beta 1/beta 2 receptor subtype ratio was approximately 80/20. At a concentration less than its low affinity (beta 2) Kl, betaxolol, a highly selective beta 1-antagonist, inhibited isoproterenol (non-selective agonist), denopamine, and prenalterol stimulation of AC, indicating that isoproterenol, denopamine, and prenalterol are all capable of stimulating AC through beta 1-receptor activation. At a concentration less than its low affinity (beta 1) Kl, ICI 118,551, a highly selective beta 2-agonist, inhibited both isoproterenol and zinterol stimulation of AC, indicating that isoproterenol and zinterol stimulate AC through beta 2-receptors. Zinterol stimulation of AC was mediated entirely by beta 2-receptors, inasmuch as 10(-7) M betaxolol had no effect on the zinterol dose-response curve and ICI 118,551 produced a degree of blockade (KB = 5.2 +/- 1.6 X 10(-9) M), consistent with the beta 2-receptor Kl of the latter (2.0 +/- .4 X 10(-9) M, p, not significant). In nonfailing myocardium, analysis of beta 1 versus beta 2 stimulation by the nonselective agonist isoproterenol revealed that the numerically small (19% of the total) beta 2 fraction accounted for the majority of the total adenylate cyclase stimulation. In failing ventricular chambers with a beta 1/beta 2 receptor subtype ratio reduced from 82/19 (nonfailing) to 64/36 (p less than 0.001) and a beta 1-receptor density reduced by 61% (p less than 0.001), maximal denopamine stimulation was reduced by 49% (p less than 0.001). Moreover, in preparations from failing heart, the component of denopamine stimulation that was inhibited by 10(-7) M betaxolol (beta 1 component) was reduced by 77% (p less than 0.05). Finally, in preparations derived from failing ventricular myocardium, beta 2-receptor density was not significantly decreased, but zinterol stimulation of AC was reduced by 32% (p less than 0.05). We conclude that heart failure results in subsensitivity to both selective beta 1 and beta 2 stimulation of adenylate cyclase, with beta 1 subsensitivity due to selective beta 1 receptor down-regulation and beta 2 subsensitivity due to partial uncoupling of beta 2 receptors from subsequent events in the beta 2-adrenergic pathway.
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PMID:Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. 256 29

Prenalterol was administered as an intravenous infusion at three incremental rates (60, 120 and 240 nmol/min) to five patients with severe cardiac failure. Haemodynamic, hormonal and metabolic variables were measured at the same time as plasma prenalterol concentrations, and the pharmacokinetics of the drug were studied by following plasma concentrations and urinary excretion during and after the infusion. Concentration-dependent increases in cardiac index, stroke index and stroke work index were observed without increases in arterial pressure, heart rate or myocardial oxygen demand. The reninangiotensin-aldosterone system was stimulated, although the extent of stimulation varied among patients. No strong correlations were found between the logarithm of the plasma prenalterol concentration and effect. Plasma clearance of the drug was lower in cardiac patients than in normal volunteers, but a large decrease in renal clearance was partially balanced by an increase in nonrenal clearance. Over the observed range of concentrations, no deviation from linearity was evident, and plasma concentrations of about 150 nmol/l were effective in improving cardiac function without significant side-effects.
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PMID:Pharmacokinetics and plasma-concentration-effect relationships of prenalterol in cardiac failure. 286 51

The immediate haemodynamic effects of prenalterol and nitroglycerine were examined in 15 patients, with severe chronic heart failure. Prenalterol was given intravenously in increasing doses of 2, 4, and 8 mg. Cardiac index increased significantly by 16%, 24%, and 32%, respectively. Heart rate increased by 16%, 19%, and 24%. Stroke volume index, systemic artery pressure, pulmonary artery pressure, and right atrial pressure did not change. Prenalterol reduced systemic vascular resistance by 15%, 17%, and 24%, respectively. Forearm blood flow and forearm vascular resistance was unchanged. Cardiac index and heart rate were not changed by 0.5 mg nitroglycerine, administered sublingually. Systolic and diastolic blood pressure were on average reduced by 14% and 12%, respectively. Systolic and diastolic pulmonary artery pressure and right atrial pressure were similarly reduced by 17%, 31%, and 39%, respectively. Nitroglycerine lowered calculated systemic vascular resistance by 11%, whereas forearm blood flow and forearm vascular resistance was unchanged. The conclusion is that prenalterol acutely increased cardiac index and improved haemodynamics in 14 out of 15 patients, mainly due to an increased heart rate. Nitroglycerine did not change cardiac index in the same group of patients.
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PMID:Prenalterol in severe congestive heart failure. I. The immediate haemodynamic effects as compared to nitroglycerine. 312 10

The aim of the study was to assess the effect of Prenalterol on cardiovascular beta adrenergic system of 12 coronary artery disease patients with a previous myocardial infarction. For this purpose, left ventricular function was assessed before and after intravenous administration of 30 gamma/Kg of Prenalterol, under a constant heart rate, provided by atrial pacing. Prenalterol induced a significant improvement of left ventricular contractility (dp/dt pos.-VCEmax-Vmax d), relaxation (dp/dt neg.-T constant), ventricular compliance (total diastolic compliance-modulus of chamber stiffness-end-diastolic compliance) and pump (ejection fraction) indices. These results suggest the potential usefulness of Prenalterol in severe acute cardiac failure.
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PMID:[Effects of Prenalterol on left ventricular function of coronary patients]. 613 12

Prenalterol, a beta 1 selective agonist, exerts a positive inotropic action in animal studies as well as in human volunteers and is effective when administered orally. To assess its immediate haemodynamic and myocardial metabolic effects, we studied the response to prenalterol (50 and 100 micrograms kg-1 given intravenously by cardiac catheterization) in 15 patients with congestive heart failure secondary to coronary artery disease or non-ischaemic cardiomyopathy. At peak effect, cardiac index increased from 2.6 +/- 0.5 to 3.2 +/- 0.8 l min-1 m2 (mean +/- S.D.) (P less than 0.001); peak rate of left ventricular pressure development rose from 963 +/- 242 to 1335 +/- 411 mmHg s-1 (P less than 0.001); left ventricular end-diastolic pressure fell from 25 +/- 6 to 17 +/- 7 mgHg (P less than 0.001); coronary sinus blood flow increased from 113 +/- 39 to 148 +/- 55 ml min-1 (P less than 0.01); myocardial oxygen consumption was augmented from 12.7 +/- 3.9 to 16.4 +/- 5.8 ml min-1 (P less than 0.001); and heart rate increased slightly (from 76 +/- 12 to 86 +/- 14 beats min-1; (P less than 0.05)). No significant changes occurred in left ventricular systolic pressure, stroke volume index, myocardial lactate extraction rate and myocardial arteriovenous oxygen difference, and no patients developed angina, ECG changes or ventricular arrhythmias. Infusion of prenalterol effectively improved haemodynamic function and cardiac metabolism in cardiomyopathy. Therefore this agent deserves further investigation to evaluate its possible role for the long-term therapy of patients with chronic heart failure.
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PMID:Haemodynamic and cardiac metabolic effects of the new beta 1 agonist prenalterol in patients with cardiac failure. 613 81

The effects of a single intravenous infusion of prenalterol, a beta 1 selective agonist, on haemodynamics (echocardiography) and venous plasma catecholamine concentration were studied in 8 patients with severe congestive heart failure. In these patients, age-adjusted plasma norepinephrine (NE) and epinephrine (E) levels before prenalterol infusion were higher compared to values found in 10 control healthy subjects (both P less than 0.01). In heart failure patients, circulating NE levels were not dissimilar in 2 samples drawn 60 and 0 minutes before commencing prenalterol infusion (772.0 +/- 131 ng/l [mean +/- SD] and 775.5 +/- 130.0 ng/l respectively). Prenalterol induced a significant improvement in the cardiac index, stroke index, ejection fraction and velocity of circumferential fiber shortening, associated with a moderate but significant decrease in peripheral vascular resistance. All these changes persisted for 60 minutes after the end of infusion. Circulating NE levels were 604.0 +/- 125 ng/l at 60 min. after start of infusion (P less than 0.01 vs pre-infusion levels) and 526.1 +/- 108 ng/l at 60 min. after the end of infusion (P less than 0.01 vs pre-infusion levels). Plasma E showed a slight decrease, which did not attain statistical significance. Heart rate and diastolic blood pressure remained unchanged during and after infusion, while systolic blood pressure increased by 10-15 mmHg during and after infusion. We conclude that a single 1-hour prenalterol infusion in patients with severe congestive heart failure induces an haemodynamic improvement associated with a reduction of previously elevated circulating NE levels. This reduction could indicate a lowering in the intensity of the afferent stimulus for the reflex sympathetic overactivity.
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PMID:Acute effects of beta 1 agonism with prenalterol on catecholamine circulating levels in patients with congestive heart failure. 614 75

The acute haemodynamic effects of oral prenalterol were studied in 14 patients with severe heart failure (NYHA class III) due to ischaemic heart disease. All had received treatment with digoxin, diuretics, and in most cases vasodilators. Prenalterol was administered at two hourly intervals to give cumulative doses of 20, 50, and 100 mg and mean plasma concentrations of 53, 97, and 175 nmol/l. Haemodynamic measurements were made two hours after each dose with Swan-Ganz catheterisation; cardiac output was measured by thermodilution. There were no significant changes in heart rate, mean arterial pressure, or pulmonary artery diastolic pressure after the drug. Cardiac index rose significantly after 50 mg and 100 mg prenalterol. Oral prenalterol has a beneficial short term haemodynamic effect in patients with severe heart failure. If this effect is sustained prenalterol may be of value in the long term management of patients with this disabling condition.
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PMID:Acute haemodynamic effects of oral prenalterol in severe heart failure. 614 24

The acute haemodynamic effects of increasing doses of parenterally administered prenalterol-a beta-adrenergic stimulating drug-were assessed in normal subjects by means of radionuclide ventriculography. Prenalterol induced dose-related increases in the left ventricular ejection fraction and the systolic pressure end-systolic volume ratio. Left ventricular end-systolic and end-diastolic volumes decreased to the same extent accounting for an unchanged stroke volume. Cardiac output increased due to a rise in the heart rate. Systolic blood pressure increased, whereas diastolic and mean blood pressure remained unchanged. Calculated total peripheral resistance decreased significantly. The maximum effect of prenalterol on cardiac performance occurred with a dose of 18 to 36 micrograms/kg. Plasma concentrations of prenalterol showed large interindividual variations. In conclusion, prenalterol improves the pump function of the normal heart and causes a fall in peripheral vascular resistance, implying a reduction of the load on the heart. These effects may prove beneficial in the treatment of acute heart failure.
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PMID:Dose-response relationship in normal subjects of prenalterol, a beta-adrenergic agonist with positive inotropic and resistance lowering effects. 615 7

Prenalterol was examined with regard to its acute intravenous effects on left ventricular function, coronary hemodynamics, and myocardial oxygen consumption, as well as for its long-term effects, by oral therapy, on left ventricular function and systemic hemodynamics. Intravenous prenalterol enhances myocardial contractility and left ventricular ejection function significantly. A decrease in total peripheral vascular resistance is effected. Myocardial oxygen consumption is only moderately increased, most probably because of the decrease in the systolic integrated wall stress of the left ventricle. The changes of coronary circulation (blood flow, resistance, arteriovenous, oxygen difference) indicate benign and metabolically induced coronary vasodilation. Long-term oral treatment of patients with severe cardiac failure by prenalterol effects significant enhancement in-left ventricular performance within the first 1-2 months of treatment; however, this effect is not present at longer therapy intervals (16-28 weeks). Tolerance development as well as the natural history of these patients may be responsible for this inotropic amelioration. There were no clinical side effects with either intravenous or oral application. It may be concluded that prenalterol is highly effective in acute cardiac failure (intravenous administration) and also in chronic heart disease (long-term oral application). However, the long-term effects are unpredictable, and tolerance development has to be considered.
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PMID:Contractile, coronary, and metabolic effects of the acute and long-term treatment of cardiac failure with prenalterol. 620 77

Prenalterol, a beta1 agonist, was given in a single blind acute intravenous study to seven patients with cardiac failure (New York Heart Association class II and III). It was then given in a double blind crossover study of sustained oral prenalterol to six of them. As a result of dose titration studies the oral dose of prenalterol given was 100 mg twice a day in all patients. Erect bicycle sprint tests were performed to exercise tolerance before and after treatment had been started. Cardiac function was assessed at rest and during graded supine bicycle exercise by determining haemodynamic indices using a Swan-Ganz catheter and radionuclide left ventricular ejection fractions. In the intravenous study cardiac function was assessed at rest and during exercise after a control infusion of dextrose and after an infusion of 5 mg prenalterol. In the oral crossover study a placebo or prenalterol were given for two periods of two weeks; at the end of each period exercise tolerance was measured and cardiac function assessed at rest and during exercise. Throughout the study period there was no change in symptoms, medication, or exercise tolerance. Intravenous prenalterol significantly improved cardiac function; left ventricular ejection fraction and cardiac index increased and left ventricular filling pressure fell both at rest and during exercise. Sustained oral treatment with prenalterol, however, did not improve resting left ventricular filling pressure or left ventricular ejection fraction at rest or during exercise but did increase heart rate at rest, and mean blood pressure and peripheral vascular resistance at rest and during exercise; in fact, during exercise left ventricular filling pressure was significantly increased while cardiac index and stroke volume index were decreased by prenalterol. Sustained oral treatment with prenalterol did not have the beneficial effects on cardiac function produced by intravenous treatment and in fact had deleterious effect on the measured indices of cardiac function during exercise.
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PMID:Acute intravenous and sustained oral treatment with the beta1 agonist prenalterol in patients with chronic severe cardiac failure. 632 84


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