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 147,016 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 (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

The influence of pimobendan and nitroprusside on hemodynamics was investigated in nine patients with idiopathic dilated cardiomyopathy (NYHA class II-III). Pimobendan and nitroprusside resulted in a comparable decrease of left ventricular end-diastolic wall stress (preload) by 46% (p less than 0.01) and 52% (p less than 0.01), respectively, and of end-systolic wall stress (afterload) by 36% (p less than 0.01) and 34% (p less than 0.01), respectively. Cardiac index increased from 3.2 +/- 0.4 to 4.2 +/- 0.8 L/min/m2 with pimobendan (p less than 0.01) and did not significantly change with nitroprusside (3.0 +/- 0.6 L/min/m2). Compared to nitroprusside, pimobendan resulted in a significant increase in stroke volume index by 37% (p less than 0.01) and maximum rate of left ventricular pressure rise by 23% (p less than 0.05). Heart rate did not significantly change with either drug. Following the application of pimobendan, there was a decrease in myocardial oxygen consumption from 14.3 +/- 5.1 to 10.6 +/- 3.8 ml/min/100 g (p less than 0.05). The ratio of myocardial oxygen consumption and systolic stress-time integral did not significantly change. Thus, in comparison with nitroprusside, pimobendan exhibits significant inotropic and vasodilating properties. The hemodynamic actions of pimobendan are associated with favorable effects on myocardial energetics.
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PMID:Effects of pimobendan on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy: comparison with nitroprusside. 247 89

Sequential hemodynamic effects of intravenous pimobendan (UD-CG 115 BS), a novel compound with positive inotropic and vasodilating properties, were investigated during left heart catheterization in nine patients with left ventricular dysfunction (ejection fraction less than or equal to 40%) and moderate congestive heart failure (NYHA classes II and III). Studies were carried out before (C) and for 60 min after intravenous administration of 5 mg of pimobendan over 1 min. Pimobendan immediately and progressively reduced systemic resistance [16 and 28% at 10 and 60 min postdrug, respectively (p less than 0.05 vs. C)] and left ventricular end diastolic pressure [from 24 +/- 3 (C) to 12 +/- 3 mm Hg at 60 min, p less than 0.001)]. Cardiac output gradually increased by 24%, but stroke volume did not, due to an equally progressive 14% rise in heart rate, whereas stroke work increased by 21% (all p less than 0.05 vs. C). Both contractility and relaxation, measured at fixed heart rates, significantly improved by 30 and 20%, respectively, at 50 min postdrug. Thus, pimobendan has immediate and prolonged arterial vasodilating effects, together with positive inotropic and lusitropic properties, resulting in an early but sustained improvement of left ventricular pump function and filling pressures.
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PMID:Hemodynamic effects of intravenous pimobendan in patients with left ventricular dysfunction. 247 91

Pimobendan (UD-CG 115 BS) was administered orally to 23 patients with congestive heart failure (functional class IV) caused by coronary artery disease (11 patients) or idiopathic dilated cardiomyopathy (12). All patients received maintenance doses of digoxin, furosemide and warfarin. Baseline data, collected during 15 hours, stayed within a 10% range. A 10-mg oral dose of pimobendan increased the heart rate from 95 +/- 20 to 109 +/- 24 beats/min (p less than 0.003). The pulmonary artery wedge pressure decreased from 23.0 +/- 5.9 to 10.1 +/- 5.2 mm Hg (p less than 0.0001), the cardiac index increased from 1.9 +/- 0.4 to 3.3 +/- 0.7 liters/min/m2 (p less than 0.0001) and the left ventricular stroke work index increased from 2,005 +/- 927 to 3,065 +/- 1,161 ml/mm Hg/m2 (p less than 0.0001). Statistically significant improvements in hemodynamic variables were still present 10 hours after the administration of pimobendan. Most patients felt better and reported no angina or other side effect, the incidence of ventricular arrhythmias was unchanged and no electrocardiographic changes suggesting ischemia were observed. Patients with severe congestive heart failure experienced a prolonged improvement of their cardiovascular condition after a single dose of pimobendan.
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PMID:Hemodynamic effects of pimobendan given orally in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. 291 61

The cardiovascular effects of the pyridazinone-derivatives pimobendan and its O-demethylmetabolite UD-CG 212 Cl (2-(4-hydroxy-phenyl)-5-(5-methyl-3-oxo-4,5-dihydro-2H-6-pyridazinyl) benzimidazole HCl) were studied in conscious pigs, employing consecutive intravenous 10 min infusions of 10, 25, 50 and 100 micrograms kg-1 min-1 and 2, 4 and 8 micrograms kg-1 min-1 respectively. Pimobendan caused dose-dependent increases in LVdP/dtmax (up to 115%) and heart rate (up to 30%), while cardiac output was slightly elevated (up to 15%) and stroke volume decreased by 12%. Left ventricular end-diastolic pressure decreased in a dose-related manner from 8.7 +/- 1.0 mmHg to 2.7 +/- 1.7 mmHg. Mean arterial blood pressure was not significantly affected because systemic vascular resistance decreased dose-dependently up to 15%. After beta-adrenoceptor blockade, the pimobendan-induced increases in heart rate and cardiac output were attenuated and the increase in LVdP/dtmax almost abolished. The responses of left ventricular end-diastolic and mean arterial blood pressure, systemic vascular resistance and stroke volume were not modified. UD-CG 212 Cl caused dose-related increases in LVdP/dtmax (up to 100%) and heart rate (up to 25%). Cardiac output was minimally elevated (up to 8%) as stroke volume decreased dose-dependently up to 15%. As systemic vascular resistance decreased up to 12%, mean arterial blood pressure was slightly reduced (5%). Left ventricular end-diastolic blood pressure decreased dose-dependently from 9.0 +/- 0.8 mmHg to 3.8 +/- 1.3 mmHg. After beta-adrenoceptor blockade, the UD-CG 212 Cl-induced increases in heart rate and LVdP/dtmax were attenuated and almost abolished and amounted up to 15% and 20%, respectively. The responses of the other systemic haemodynamic parameters were not significantly modified. We conclude that pimobendan and UD-CG 212 Cl are compounds with marked positive inotropic and venodilator properties in the conscious pig. The attenuation of the inotropic effects by pretreatment with propranolol strongly suggests that, in the conscious pig, the beta-adrenergic system is significantly involved in the positive inotropic actions. The lack of effect of beta-adrenoceptor blockade on the vasodilator responses to both compounds suggest a mechanism not related to beta-adrenergic activity.
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PMID:Systemic haemodynamic actions of pimobendan (UD-CG 115 BS) and its O-demethylmetabolite UD-CG 212 Cl in the conscious pig. 360 69

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

We examined and compared the effects of levosimendan, a new myofilament calcium sensitizer with phosphodiesterase inhibiting activity, pimobendan, and milrinone on left ventricular-arterial coupling and mechanical efficiency in 21 experiments performed in open-chest, barbiturate-anesthetized dogs instrumented for measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped catheter), +dP/dt, and LV volume (conductance catheter). Myocardial contractility was assessed with the end-systolic pressure-volume relation (Ees) and preload recruitable stroke work (Msw) generated from a series of differentially loaded LV pressure-volume diagrams. LV-arterial coupling and mechanical efficiency were determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of end-systolic arterial pressure to stroke volume) and the ratio of stroke work (SW) to pressure-volume area (PVA), respectively. Levosimendan (0.75, 1.5, and 3.0 micrograms.kg-1.min-1) significantly (p < 0.05) increased heart rate, +dP/dt, and ejection fraction (EF) and decreased mean arterial pressure (MAP), pressure-work index (PWI; an estimate of myocardial-oxygen consumption), and LV systolic and end-diastolic pressures (LVSP and LVEDP) and volumes (EDV and ESV). Levosimendan-induced augmentation of myocardial contractility (Ees, Msw and +dP/dt) and reductions in LV afterload (Ea) caused increases in the Ees/Ea ratio (0.61 +/- 0.10 during control to 3.3 +/- 0.7 during the high dose) consistent with enhancement of LV-arterial coupling. Levosimendan increased SW/PVA (0.48 +/- 0.05 during control to 0.84 +/- 0.04 during the high dose), indicating this drug improves the transfer of myocardial potential energy to external work. Levosimendan also increased the ratio of SW to PWI (109 +/- 18 during control to 255 +/- 50 mmHg.min.100g during the high dose), suggesting that myocardial metabolic efficiency was improved as well. Like levosimendan, pimobendan and milrinone (10, 20, and 40 and 1.0, 2.0, and 4.0 micrograms.kg-1.min-1, respectively) increased HR, +dP/dt, EF, Ees, and Msw and decreased MAP, LVSP, LVEDP, EDV, ESV, and Ea. In contrast to levosimendan, neither agent reduced PWI. Pimobendan and milrinone caused dose-related increases in Ees/Ea, SW/PVA, and SW/PWI. The results indicate that levosimendan, pimobendan, and milrinone augment myocardial contractility, produce venous and arteriolar vasodilation, and enhance LV-arterial coupling and mechanical efficiency in open-chest, barbiturate-anesthetized dogs.
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PMID:Comparison of the effects of levosimendan, pimobendan, and milrinone on canine left ventricular-arterial coupling and mechanical efficiency. 887 79

Pimobendan has a dual mechanism of action: it increases myocardial contractility by increasing calcium sensitization to troponin C and it promotes vasodilation by inhibiting PDEIII. This study examined the effects of pimobendan on cardiac function, hemodynamics, and neurohormonal factors in dogs with mild mitral regurgitation (MR). The dogs were given 0.25 mg/kg of pimobendan orally every 12 hr for 4 weeks. With pimobendan, the heart rate and stroke volume did not change, but the systolic blood pressure gradually decreased and the degree of mitral valve regurgitation tended to decrease. Renal blood flow was significantly increased and the glomerular filtration rate was slightly increased at 2 and 4 weeks. Furthermore, over the 4-week period, the plasma norepinephrine concentration decreased significantly, the systolic index increased slightly, the left atrial diameter and the left ventricular diameters decreased significantly, and the heart size improved. Given these results, pimobendan appears to be useful for treating MR in dogs. However, further long-term studies of pimobendan involving a larger number of dogs with mild and moderate MR are needed to establish the safety of pimobendan and document improvements in quality of life.
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PMID:Effects of pimobendan for mitral valve regurgitation in dogs. 1748 24