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

In this study, the acute hemodynamic effects of pimobendan (2.5 mg), a new drug, was compared with that of captopril (12.5 mg) in the same 8 patients with chronic heart failure (NYHA class II-III); 3 with dilated cardiomyopathy and 5 with regurgitant valvular heart disease. The hemodynamics were serially assessed before and after drug administration for at most 6 hours. Pimobendan reduced mean blood pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, right atrial pressure, total systemic vascular resistance, and total pulmonary vascular resistance but it increased heart rate. By contrast, captopril reduced mean blood pressure and double product. No significant changes were noted in the cardiac index, stroke volume index, AV-O2 difference or the arterial oxygen pressure between the 2 drugs. In conclusion, pimobendan seems to function as a strong arterio-veno-dilator rather than as an inotropic agent in patients with chronic heart failure.
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PMID:[Acute hemodynamic effects of pimobendan and captopril: a comparative study in the same patients with chronic heart failure]. 134 39

Pimobendan (10 mg on day 1, then 5 mg twice daily for 28 days) was administered orally to nine patients in class III-IV stable congestive heart failure. On day 1, pimobendan appeared in plasma within 30 min, its plasma concentration peaked at 39 +/- 23 ng/ml after 1.5 h, and then decreased with a half-life of 1.44 +/- 0.94 h. Concentrations of its major metabolite UD-CG 212 peaked 3 h after drug intake, at 24 +/- 7 ng/ml. The time course of plasma concentrations was similar on days 1, 2, and 28. Cardiac index increased from 2.2 +/- 0.5 to 2.8 +/- 0.4 L.min-1.m-2 (p = 0.0001) on day 1, from 2.8 +/- 0.5 to 3.4 +/- 0.4 L.min-1.m-2 (p = 0.0032) on day 2, and stayed at 2.7 +/- 0.6 and 2.7 +/- 0.9 L.min-1.m-2 (p = 0.7895) on day 28. On day 1, pulmonary capillary wedge pressure decreased from 16 +/- 7 to 6 +/- 5 mm Hg (p = 0.0001), from 10 +/- 7 to 7 +/- 8 mm Hg (p = 0.0001) on day 2, and from 9 +/- 7 to 5 +/- 3 mm Hg (p = 0.0275) on day 28. Cardiovascular effects of pimobendan were independent of plasma concentrations. All patients improved by at least one NYHA functional class; exercise tolerance increased. No side effect was observed, but two patients died suddenly: Arrhythmogenicity should be ruled out before pimobendan is recommended for treatment of heart failure.
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PMID:Cardiovascular effects and plasma level profile of pimobendan (UD-CG 115 BS) and its metabolite UD-CG 212 in patients with congestive heart failure after single and repeated oral dosing. 247 6

Pimobendan (UD-CG 115 BS) is a potent positive inotropic agent with vasodilatory properties. This hemodynamic profile was demonstrated in conscious rabbits chronically instrumented with Doppler flow probes. Pimobendan (10, 30, 100, and 300 micrograms/kg i.v.) increased cardiac output, stroke volume, heart rate, and mesenteric, renal, and hindquarter blood flow velocities, and decreased diastolic blood pressure. The positive inotropic effects of pimobendan and its effects on pre- and afterload were also shown in dogs with propranolol-induced depressed myocardial function. Pimobendan exhibited strong effects on stroke volume (up to 59%) and pulmonary capillary wedge pressure (up to -84%). The substance increased left ventricular (LV) dp/dtmax up to 150% and also had favorable effects on renal blood flow. Left ventricular function curves showed the usefulness of pimobendan in this acute heart failure model. Pimobendan is well absorbed and its duration of action is long. Positive inotropic effects of pimobendan were observed for 8-12 h after oral administration of 0.1-1 mg/kg to conscious dogs. It is concluded that pimobendan produces cardiovascular effects that may be useful in the treatment of congestive heart failure.
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PMID:Hemodynamic profile of the cardiotonic agent pimobendan. 247 84

Pimobendan was administered orally (10 mg single dose on day 1, then 5 mg twice daily for 4 weeks) to nine patients with chronic heart failure undergoing hemodynamic monitoring. The time course of changes in plasma concentrations of pimobendan and of its major active metabolite. UD-CG 212 CL, was similar on days 1, 2, and 28. Pimobendan plasma levels peaked 1.5-2.0 h after drug intake: plasma concentrations of UD-CG 212 CL reached a maximum 1 h later; the terminal half-life of pimobendan in plasma varied between 1.44 +/- 0.94 h on day 1 and 1.19 +/- 0.36 h on day 2. Initially, cardiovascular variables changed with increasing plasma drug levels and reached a maximum 4 h after pimobendan intake; later, we found no correlation between plasma concentrations and hemodynamic effects. A steady state of hemodynamic improvement was achieved after 4 weeks of maintenance therapy with pimobendan. Baseline pulmonary capillary wedge pressure dropped from 16 +/- 7 mm Hg on day 1 to 5 +/- 3 mm Hg at noon on day 28 (-69%; p less than 0.001), and baseline cardiac index increased from 2.2 +/- 0.5 L/min/m2 on day 1 to 2.7 +/- 0.9 L/min/m2 on day 28 (+23%; p less than 0.01). Pimobendan is a long-acting drug that effectively improves cardiac performance in patients with chronic congestive heart failure.
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PMID:Correlations between the cardiovascular effects of pimobendan and plasma concentrations of the parent compound and of its major active metabolite, UD-CG 212 CL, in patients with congestive heart failure. 247 94

Intravenous infusions of 0.01-0.1 mg X kg-1 X min-1 of pimobendan, a benzimidazole-pyridazinone derivative in pigs with normal coronary circulation caused dose-dependent changes in heart rate (10-35%), left ventricular systolic pressure (-5 to -45%), left ventricular filling pressure (-20 to -40%) but had only a minor effect on the maximum rate of rise of left ventricular pressure (max LVdP/dt; 10-20%). The decrease in mean arterial blood pressure was primarily due to systemic vasodilation; peripheral resistance and cardiac output decreased by up to 40 and 14%, respectively. Vasodilation occurred in several vascular beds, but was particularly pronounced in the adrenals, stomach, small intestine and myocardium. Although the increase in myocardial blood flow favoured the epicardium, vascular conductance in both the endo- and epicardial layers was significantly increased. Myocardial O2 consumption (MVO2) was not affected despite the increase in heart rate. Bolus injections of 0.1-0.5 mg X kg-1 pimobendan produced similar changes in all haemodynamic variables, except max LVdP/dt which now increased by 30-70%. As in the infusion experiments, cardiac output tended to decrease due to a pronounced reduction in ventricular preload probably as a result of venodilation and the consequent reduction in cardiac filling. However, in animals where max LVdP/dt and cardiac output were reduced and pre- and/or after-load were increased by partial occlusion of the left anterior descending coronary artery, pimobendan clearly increased both max LVdP/dt and cardiac output. Pretreatment with propranolol did not modify any of the cardiovascular responses to pimobendan, thereby excluding the involvement of a beta-adrenoceptor mechanism. Pimobendan is thus a compound with vasodilator and positive inotropic properties that improves cardiac output in animals with severe myocardial ischaemia. The finding that the mild tachycardia caused by pimobendan was not accompanied by an increase in MVO2 warrants investigation to evaluate its usefulness in the treatment of heart failure.
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PMID:Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties. 287 84

Left ventricular (LV) inotropic and lusitropic responses to a calcium sensitizer, pimobendan, were compared between normal and failing hearts. Heart failure was induced by rapid ventricular pacing in 6 dogs instrumented with a micromanometer and a conductance catheter. The effects of pimobendan were evaluated in the conscious state before and after development of heart failure. Pimobendan dose-dependently increased the slope of the end-systolic pressure-volume (P-V) relation (Ees) in both normal and failing hearts, whereas its magnitude was markedly attenuated in failing hearts. Heart rate (HR) was increased by pimobendan in normal heart but did not change in failing heart. LV relaxation, assessed by peak -dP/dt and the time constant of isovolumic pressure decay (Td), was substantially improved to the same extent in failing and normal hearts. Consequently, Ees and Td exhibited a hyperbolic relation over a wide range of contractility states. In normal heart, pimobendan caused a leftward shift of the diastolic P-V relation while maintaining a similar curve. In failing heart, however, this relation shifted directly downward with a concomitant increase in end-diastolic volume, indicating a reduction in the constraints on LV distention and a resultant increase in preload reserve. Thus, pimobendan accelerated LV isovolumic relaxation and improved distensibility in conscious dogs with tachycardia-induced heart failure despite the marked attenuation of inotropic responses.
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PMID:Disparate inotropic and lusitropic responses to pimobendan in conscious dogs with tachycardia-induced heart failure. 751 57

In contrast to cyclic AMP-dependent positive inotropes, the calcium-sensitizer and partial phosphodiesterase (PDE) inhibitor pimobendan may induce beneficial effects in heart failure. However, its effect on relaxation, myocardial energetics and neurohormones are unknown. Twelve patients with heart failure, New York Heart Association (NYHA) classification II-III, due to ischemic cardiomyopathy, were studied for 1 h after they received 5 mg pimobendan intravenously (i.v.). Pimobendan progressively reduced systemic resistance and left ventricular end-diastolic pressure (LVEDP) (22 and 50%, respectively) and improved isovolumetric contractility and relaxation parameters by 30% (all p < 0.05 vs. control). LV end-diastolic and end-systolic volumes (LVEDV, LVESV) decreased significantly by 20 and 19%, respectively. Cardiac output (CO) increased by 17% due to a simultaneous increase in heart rate (HR) from 75 +/- 3 to 86 +/- 5 beats/min (mean +/- SEM, p < 0.05). Pimobendan did not change coronary hemodynamics, but myocardial O2 extraction and consumption were decreased significantly by 18 and 20%, respectively. Catecholamines, angiotensin II (AII), and aldosterone levels did not change significantly. In contrast, arterial and coronary venous renin increased significantly from 57 +/- 17 and 53 +/- 14.7 microM/h at control to 69 +/- 20 and 69 +/- 20 microM/h, respectively, 60 min after pimobendan administration. Simultaneously, cardiac renin uptake at baseline (0.449 +/- 0.185 mumol/min) changed to release (-0.071 +/- 0.145 mumol/min, p < 0.05). Serious side effects did not occur. Thus, pimobendan had progressive positive inotropic and lusitropic effects, diminished preload and afterload despite modest stimulation of plasma renin activity (PRA), and reduced systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic, neurohumoral, and myocardial energetic effects of pimobendan, a novel calcium-sensitizing compound, in patients with mild to moderate heart failure. 753 50

Pimobendan is a novel cardiotonic vasodilator (inodilator) which derives its inotropic activity from a combination of phosphodiesterase III inhibition and sensitisation of myocardial contractile proteins to calcium. The acute haemodynamic benefits of pimobendan (2.5 to 10mg orally; 5 to 10mg intravenously) seen in patients maintained on conventional diuretic, digitalis and vasodilator therapy for chronic heart failure (increases in cardiac output and stroke volume, and reductions in left ventricular preload and afterload) persisted on short term (1 month) therapy, and showed only limited evidence of attenuation on longer term (6 months) oral therapy with pimobendan 2.5 or 5mg twice daily. Adjunctive therapy with pimobendan 1.25 to 5mg twice daily for periods of 3 to 6 months improved exercise tolerance on symptom-limited exercise testing, New York Heart Association (NYHA) functional class, and quality of life, and additionally reduced the need for hospitalisation in patients with moderate to severe chronic heart failure. Pimobendan appears to be well tolerated at therapeutic doses (1.25 to 5mg twice daily) in patients with chronic heart failure, and preliminary indications suggest that it is largely devoid of the proarrhythmic effects of classical phosphodiesterase III inhibitors. Although information regarding the long term effects of pimobendan on mortality is currently lacking, the drug nevertheless shows potential benefit as an adjunctive therapy in patients with chronic heart failure.
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PMID:Pimobendan. A review of its pharmacology and therapeutic potential in congestive heart failure. 804 44

The cardiotonic effect of pimobendan was studied in 6 dog heart-lung preparations in which cardiac function had been severely depressed by pentobarbital. Pimobendan in doses of 1-10 mg improved cardiac function in a dose-dependent manner and at 10 mg improved it beyond the control. These doses of pimobendan, however, produced neither a significant increase in heart rate nor arrhythmias. The results indicate that the drug may be of use in the treatment of heart failure.
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PMID:Improvement of cardiac performance by pimobendan, a new cardiotonic drug, in the experimental failing dog heart. 831 18

There has been an intensive search for safe and clinically effective inotropic agents for use as adjunctive therapy in patients with advanced heart failure. Pimobendan is a benzimidazole-pyridazinone derivative with calcium-sensitizing properties that increases myocardial contractile force without increasing intracellular calcium. This review summarizes the data from five controlled, randomized prospective trials of pimobendan that demonstrate significant improvements in exercise capacity and quality of life in patients with heart failure. The clinical benefits of pimobendan found in these trials contrast with the adverse experience noted previously with milrinone and enoximone. This may be related to the different mechanism of action of pimobendan or to a study design that permitted examination of a lower dosage. These cumulative data suggest that pimobendan may have a useful adjunctive role in heart failure and that further assessment of its effects on overall mortality is needed.
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PMID:Effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. 914 32


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