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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pressure-volume relation analysis was used to independently quantify changes in ventricular contractile performance and vascular loading in intact anesthetized dogs before and after a single bolus of intravenous amrinone. Ventricular systolic property changes were characterized by the end-systolic elastance (Ees = slope of the end-systolic pressure-volume relation) and arterial properties by the effective arterial elastance (Ea = end-systolic pressure/stroke volume ratio). Pressure-volume data were obtained by the conductance catheter technique with loading varied by transient inferior vena cava occlusion. Amrinone induced a 27% increase in ejection fraction at 10 min (from 44% to 56%) as a result of both a significant rise in contractility (mean Ees 4 +/- 2 to 6 +/- 3 mm Hg/ml, p less than 0.001) and simultaneous reduction in arterial loading (Ea reduction from 6 +/- 2 mm Hg/ml to 5 mm Hg/ml, p less than 0.001). Over the subsequent 30 min, Ea revealed a significant recovery toward baseline, whereas Ees was less altered. Mean percent changes (% delta) in both variables were linearly correlated: % delta Ea = -1.6 x % delta Ees + 3.1, r = 0.96, p less than 0.001. In addition to separating ventricular from vascular property changes, the pressure-volume coupling framework was used to predict net pump performance (ejection fraction). Model predictions showed good agreement with experimental data. Thus, pressure-volume relations can be used to separately quantitate simultaneous changes in ventricular and vascular loading properties in vivo produced by pharmacologic agents with complex actions. Use of this approach in drug testing in humans should simplify data interpretation regarding mechanisms of action in specific clinical settings.
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PMID:Pressure-volume analysis as a method for quantifying simultaneous drug (amrinone) effects on arterial load and contractile state in vivo. 238 44

The comparative haemodynamic dose-response effects of intravenous (i.v.) amrinone and dobutamine were evaluated in 20 male patients with haemodynamic (pulmonary artery occluded pressure (PAOP) greater than 20 mm Hg) and radiographic left heart failure following a recent myocardial infarction. Following a 1-h control period, 10 patients were each randomised to amrinone (800, 1,600, or 3,200 micrograms/kg/h) or dobutamine (200, 400, or 800 micrograms/kg/h) sequentially infused for 30 min at each dose level; haemodynamic parameters were recorded at the end of each infusion period. Amrinone reduced systemic arterial blood pressure and vascular resistance index with a moderately increased heart rate; PAOP (-10 mm Hg; p less than 0.01) fell substantially without change in cardiac or stroke work indices. Dobutamine increased systemic arterial blood pressure, heart rate, and stroke work index at an unchanged PAOP; cardiac index (+0.7 L/min/m2; 25%; p less than 0.01) increased. Systemic vascular resistance index was significantly reduced by both drugs. Thus, dobutamine increased cardiac index at an unchanged PAOP; myocardial stroke work increased. Amrinone had lesser effect on cardiac pumping but reduced PAOP (preload) at an unchanged stroke work. The implications of these differential actions for the clinical therapy of myocardial infarction deserves further evaluation.
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PMID:Comparative haemodynamic dose-response effects of dobutamine and amrinone in left ventricular failure complicating acute myocardial infarction. 243 89

The purpose of the present study was to induce left ventricular failure in anesthetized dogs by repeated ventricular fibrillation and then to determine if amrinone is effective in circulatory support by comparing the effects of amrinone and dobutamine. After the repetitive ventricular fibrillation, mean arterial pressure and stroke volume index decreased, pulmonary capillary wedge pressure (PCWP) increased, and acute left ventricular failure occurred. Thereafter, dogs were divided into the following four groups. In Group C (n = 6), normal saline was administered; in Group D (n = 6), dobutamine was administered at 7 micrograms/kg/min; and in Groups A40 (n = 6) and A80 (n = 7), amrinone was administered at 40 micrograms/kg/min and 80 micrograms/kg/min, respectively. Stroke volume index increased by 78% in Group D and 46% in both Groups A40 and A80. Pulmonary capillary wedge pressure decreased by 44% in Group A40 and 38% in Group A80, but remained unchanged in Group D. Similarly, total peripheral resistance decreased by 32% in Group A40, 29% in Group A80, but remained unchanged in Group D. These results suggest that amrinone increased cardiac output and decreased both preload and afterload. In the coronary circulation, both drugs caused direct coronary vasodilation since they increased myocardial oxygen supply in excess of the increase in myocardial oxygen demand. Neither drug produced signs of myocardial ischemia, as indicated by myocardial lactate metabolism. Amrinone should be a useful drug after open heart surgery, especially in cases where significant adverse effects of catecholamines occur or where a low-output state with increased preload and afterload exists.
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PMID:Comparison of the effects of amrinone and dobutamine on hemodynamics and myocardial oxygen balance in dogs with experimental left ventricular failure. 252 Sep 16

The direct negative inotropic actions of calcium channel blockers limit the use of these otherwise effective systemic and coronary vasodilators in patients with heart failure. We studied the effects of amrinone pretreatment on the dose--hemodynamic response curve of diltiazem in order to test the hypothesis that amrinone might potentiate diltiazem's positive effects in anesthetized dogs. The control group (no pretreatment, n = 6) had a typical dose-related response to diltiazem (50, 100, and 150 micrograms/kg): coronary and systemic vasodilation, increased stroke volume, and no change in myocardial work and power. Amrinone pretreatment of the study group (n = 7) altered the hemodynamic response, thus maximal systemic vasodilation and stroke volume increase at a lower diltiazem dose, a 15 to 35% increase in myocardial work and power, and more profound coronary vasodilation. We propose that amrinone, by inhibiting phosphodiesterase, potentiates diltiazem vasodilation and reflexly secreted catecholamines' actions on the heart. This positive interaction may permit effective use of lower doses of diltiazem, thus circumventing its dose-limiting direct negative effects while still profitting from beneficial peripheral, reflex, and coronary actions.
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PMID:Positive hemodynamic interaction between amrinone and diltiazem in anesthetized dogs. 259 32

Hemodynamic effects of intravenous administration of amrinone include increases in dP/dt, cardiac output, and stroke work with decreases in left ventricular filling pressure and systemic vascular resistance. Unlike other injectable positive inotropic agents, it does not increase myocardial oxygen consumption, a distinct advantage in patients with coexisting ischemic disease. Amrinone does not have deleterious effects on atrioventricular conduction and appears to have little arrhythmogenic potential. Side effects of intravenous administration are generally minor but include a reversible thrombocytopenia. Additional studies conducted in short-term low-output states are needed to define more completely its role in the treatment of this condition.
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PMID:Clinical effects of intravenous amrinone in patients with congestive heart failure. 351 Jul 75

This study was designed to assess the dose-dependent effects of amrinone (1, 2 and 4 mg/kg i.v.) on hemodynamics, myocardial blood flow and myocardial oxygen consumption in anesthetised closed chest dogs (n = 8). Heart rate (HR), cardiac output, mean aortic pressure (MAP), left ventricular end-diastolic pressure (LVEDP), maximum dp/dt (dp/dtmax), myocardial blood flow (MBF) and aorto-coronary sinus oxygen difference (AVDO2 cor) were measured. Cardiac index (CI), stroke volume index (SVI), ejection fraction (EF), total peripheral resistance (TPR), coronary vascular resistance (CVR) and myocardial oxygen consumption (MVO2) were calculated from standard formulas. Amrinone improved myocardial pump function by a direct positive inotropic effect on the myocardium. EF and SVI increased to a maximal degree with 1 mg/kg amrinone (28% resp. 30%). dp/dtmax increased dose dependent (46, 64, 71%). Following a systemic vasodilation due to amrinone, left ventricular filling pressure and TPR decreased significantly. With 1 and 2 mg/kg amrinone MAP remained unchanged. 4 mg/kg produced a distinct fall in MAP accompanied by an increase in HR. The improvement in myocardial contractility did not cause a comparable increase of myocardial oxygen consumption. Due to an unloading of the heart 1 and 2 mg/kg amrinone induced no significant and prolonged augmentation of the myocardial oxygen demand. In the coronary circulation a non energy dependent vasodilation occurred followed by a marked decrease of AVDO2 cor (10, 18, 28%).
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PMID:[Dose-dependent effect of amrinone on hemodynamics, myocardial circulation and myocardial energy requirement. An experimental study]. 399 53

Inotropic support with digoxin is commonly used in patients with left ventricular volume overload due to ventricular septal defect (VSD). However, the hemodynamic consequences of inotropic agents with VSD have not been experimentally explored. We studied two inotropic agents, digoxin and amrinone, in chronically instrumented lambs with left ventricular volume overload due to a surgically created VSD. Intravenous digoxin (40 micrograms/kg) produced serum levels of 3.5 +/- 0.9 ng/ml (mean +/- SD) in seven lambs 60 min after administration, reduced the heart rate by 16% (172 to 149 beats/min, p less than 0.05), increased the stroke volume 16% (29.8 to 34.5 ml/beat, p less than 0.05) but did not significantly alter the systemic flow index (Qs), the pulmonary flow index (Qp), or the volume of left to right shunt (QL-R, 6.74 to 6.77 liter/min/m2). The mean left atrial pressure (LA) was unchanged (17.6 versus 17.1 mm Hg) following digoxin. Chronic digoxin use in four lambs for 4 days (25 +/- 8 micrograms/kg/8 h) produced trough serum levels of 1.2 +/- 0.2 ng/ml. There was no additional hemodynamic effect compared to acute digoxin, the Qp/Qs ratio was unchanged (3.10 versus 3.08) and evidence of left ventricular volume overload (LA - 14.0 versus 13.4) was unchanged. Amrinone lowered the systemic resistance index in a dose dependent fashion. The peak reduction of 20% (25.3 to 20.3 U/m2, p less than 0.01) occurred at 20 min after an intravenous (3 mg/kg) bolus in seven lambs. The Qs increased from 2.58 to 3.10 liter/min/m2 (p less than 0.01). The Qp was unchanged, thus the Qp/Qs ratio was lowered by 16% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic consequences of inotropic support with digoxin or amrinone in lambs with ventricular septal defect. 404 55

The effects of 3 types of vasoactive agents, hydralazine, nifedipine and amrinone, were evaluated in 7 patients with primary pulmonary hypertension (PPH). Hemodynamic values were measured before and after drug administration in every patient. All drugs increased cardiac output and reduced both systemic and pulmonary resistance in the patients studied. Only nifedipine significantly reduced pulmonary artery (PA) pressure (6 +/- 5 mm Hg). In addition, it decreased pulmonary resistance to a greater degree than systemic resistance in 2 of the 7 patients, suggesting that nifedipine can cause selective pulmonary vasodilation in some patients. Hydralazine appeared to increase cardiac output and stroke volume by reducing systemic resistance. There was no evidence of direct pulmonary vasodilating effects; it decreased systemic resistance more than pulmonary resistance in every case. The increase in cardiac output from amrinone was secondary to a decrease in systemic arterial pressure with reflex tachycardia; stroke volume was unchanged. Amrinone had little pulmonary effect in all but 1 patient, in whom it substantially reduced PA pressure and pulmonary resistance. The mechanism of action of these 3 drugs in PPH differs. Nifedipine holds the most promise as an effective pulmonary vasodilator. A study of the effects of long-term administration of nifedipine in PPH is warranted.
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PMID:Comparative actions of hydralazine, nifedipine and amrinone in primary pulmonary hypertension. 663 31

Compared with isolated heart muscle and Langendorff preparations, the isolated, working heart preparation allows a more complete analysis of cardiac function and metabolism. We have studied the effects of amrinone 20 micrograms/ml and 200 micrograms/ml on the isolated perfused working guinea-pig heart. We have measured: heart rate (HR), mean systolic aortic pressure (SP), aortic flow (AF), coronary flow (CF), total cardiac output (CO), and calculated the stroke volume (SV) and the rate of external work (W). The rates of oxygen consumption (VO2) and lactate production (Lact) were also measured and the external efficiency (Eff) calculated. Hearts were allowed to fail spontaneously after work for 90 min. Amrinone was then added at the required concentration to the perfusion medium. Amrinone 20 micrograms/ml, increased AF, CF, CO, SV, W and VO2. HR was slightly but significantly increased. Lact and Eff were not altered. Amrinone 200 micrograms/ml substantially increased CF and VO2, but it increased slightly and not significantly AF, CO, SV and W, suggesting the predominance of the coronary vasodilating effect of amrinone at higher doses. Lact and Eff remained unchanged. The positive chronotropic effect was of the same magnitude than that observed with the lower dose. No arrhythmias occurred with either concentration. These results would suggest that amrinone is a positive inotropic drug with vasodilating properties at higher doses, and weak positive chronotropic effect. It stimulates aerobic but not anaerobic metabolism of the heart.
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PMID:The effects of amrinone on cardiac function, oxygen consumption and lactate production of an isolated, perfused, working guinea-pig heart. 688 99

Amrinone has been shown to exhibit a potent inotropic effect in patients with heart failure secondary to congestive cardiomyopathy, but its effects on myocardial oxygen consumption (MVO2) and coronary blood flow (CBF) are unknown. Accordingly, the hemodynamic, myocardial metabolic and ECG responses to amrinone (2.5 mg/kg i.v. over 1 hour) were measured in nine patients with congestive heart failure secondary to coronary artery disease. Increases were observed in cardiac index (1.3 +/- 0.4 to 2.2 +/- 0.7 l/min/m2) and left ventricular stroke work (10.6 +/- 3.0 to 19.2 +/- 6.3 g-m/m2), and decreases in mean pulmonary wedge (31 +/- 5 to 26 +/- 4 mm Hg), mean pulmonary artery (44 +/- 8 to 36 +/- 7 mm Hg) and mean right atrial pressures (18 +/- 4 to 10 +/- 4 mm Hg), myocardial arteriovenous oxygen difference (129 +/- 19 to 109 +/- 17 ml/l), CBF (215 +/- 117 to 178 +/- 84 ml/min) and MVO2 (27 +/- 14 to 19 +/- 9 ml/min). All changes were significant (p less than 0.01). No significant changes occurred in aortic mean pressure, heart rate, myocardial lactate extraction or ECG, and no patient developed angina. In explaining the decline in MVO2, it is possible that the increase in contractility was more than offset by the reductions in preload and afterload. The amrinone-induced hemodynamic improvement in patients with congestive heart failure secondary to coronary artery disease was associated with reductions in MVO2 and CBF and no evidence of myocardial ischemia.
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PMID:Effects of amrinone on myocardial energy metabolism and hemodynamics in patients with severe congestive heart failure due to coronary artery disease. 737 83


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