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

To assess their comparative effects on hemodynamics, nitroprusside, dobutamine and enoximone were sequentially administered to 10 patients with severe congestive heart failure. Nitroprusside, dobutamine (at 10 micrograms/kg/min) and enoximone (at 2 mg/kg) increased stroke volume index to a similar extent (31%, 34% and 36%, respectively). Enoximone produced less tachycardia than dobutamine and, consequently, a smaller improvement in cardiac index. Mean arterial pressure was not altered by dobutamine but was reduced 9% by enoximone, 2 mg/kg. This finding accounts for the larger (although not significant) increase in left ventricular stroke work index observed with dobutamine compared with enoximone. Ventricular filling pressures and vascular resistances were significantly decreased by all 3 drugs (p = 0.001). All 3 drugs improved cardiac pump function when assessed by the increase in stroke index to a similar extent; however, enoximone (2 mg/kg) resulted in less hypotension than nitroprusside (mean arterial pressure -9% vs -22%, p = 0.0001) and in less tachycardia than dobutamine 10 micrograms/kg/min. Those differences in mode of action account for the variations observed in the heart rate-blood pressure product (dobutamine 10 micrograms/kg/min, +18%, enoximone 2 mg/kg, -5%, p = 0.003). Enoximone thus appears to be of great value in the management of severe congestive heart failure by its combination of vasodilatory and inotropic properties. Enoximone (2 mg/kg) provides a clinically significant increase in cardiac index, a clear reduction of ventricular filling pressures, a moderate reduction of mean arterial pressure and only minor changes of heart rate and of rate pressure product.
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PMID:Comparative effects on hemodynamics of enoximone (MDL 17,043), dobutamine and nitroprusside in severe congestive heart failure. 295 68

The acute effects of enoximone on left ventricular (LV) function, myocardial oxygen metabolism and central and systemic hemodynamics were investigated in 12 patients with idiopathic dilated cardiomyopathy. Enoximone was administered intravenously at a rate of 12.5 mg/min; the average dose was 1.42 mg/kg. LV systolic pressure decreased significantly (p less than 0.01) from 128 +/- 18 to 96 +/- 16 mm Hg (mean +/- standard deviation), LV end-diastolic pressure from 16 +/- 3 to 5 +/- 3 mm Hg, LV end-diastolic volume from 288 +/- 43 to 210 +/- 58 ml, LV end-diastolic wall stress from 33 +/- 15 to 11 +/- 5 10(3) dynes/cm2 and LV peak systolic wall stress from 243 +/- 73 to 159 +/- 42 10(3) dynes/cm2. Heart rate increased from 86 +/- 18 to 100 +/- 20 beats/min, ejection fraction from 43 +/- 7 to 52 +/- 14% (p less than 0.05). Cardiac index, stroke volume index and dP/dtmax did not change significantly. Systemic vascular resistance decreased significantly (p less than 0.01) from 1,311 +/- 444 to 1,027 +/- 356 dynes s cm-5, mean pulmonary artery pressure from 13 +/- 6 to 8 +/- 2 mm Hg, mean right atrial pressure from 4 +/- 2 to 2.6 +/- 2 mm Hg and mean arterial pressure from 95 +/- 13 to 74 +/- 13 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac energetics after intravenous enoximone in idiopathic dilated cardiomyopathy. 295 69

Twelve patients with congestive heart failure underwent a double-blind, placebo-controlled study for the purpose of examining the central and regional hemodynamic effects of first-dose (1 and 2 mg/kg) oral enoximone, a new phosphodiesterase III inhibitor. Enoximone augmented cardiac output, generally through a positive chronotropic response. Indices of left ventricular contractility, specifically stroke volume, delta P/delta t, fractional shortening rate, and the duration of the preejection period, were only modestly enhanced by enoximone. At 2 mg/kg, systemic vascular resistance fell below baseline values without affecting systemic blood pressure; these parameters were not altered by the 1 mg/kg dose. Both pulmonary artery pressure and pulmonary vascular resistance dropped below baseline and below placebo control for the 2 mg/kg dose. Enoximone at 2 mg/kg lowered right and left heart filling pressures below baseline. Examination of regional hemodynamic responses to both doses demonstrated a reduction in limb vascular resistance and an increase in limb blood flow proportional to the concomitant increase in cardiac output. Renal and hepatic-splanchnic blood flow and vascular resistances were not altered by enoximone. First-dose oral enoximone (1 and 2 mg/kg) alters hemodynamics in heart failure by predominant vasodilatation, particularly of limb-musculoskeletal and pulmonary vascular beds, some positive chronotropism, and modest positive inotropism.
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PMID:Central and regional hemodynamic effects of oral enoximone in congestive heart failure: a double-blind, placebo-controlled study. 296 46

Thirteen patients in severe cardiogenic shock, persisting despite the use of adrenergic agents, were treated with enoximone, a recently available phosphodiesterase inhibitor. Cardiogenic shock was characterized by low cardiac output (less than 2.5 liter.min-1.m-2), elevated pulmonary artery balloon-occluded pressure (greater than or equal to 15 mm Hg), decreased urine output (less than 20 ml.hour-1) and increased blood lactate (greater than or equal to 2.0 mEq.liter-1). Ten patients were mechanically ventilated. A short-term intravenous infusion of 0.5 mg.kg-1 in 20 minutes of enoximone resulted in significant increases in cardiac index (from 1.8 +/- 0.3 to 2.9 +/- 0.3 liter.min-1.m-2, p less than 0.001) and stroke index (from 17.8 +/- 3.3 to 21.9 +/- 5.1 ml.m-2, p less than 0.001) and significant decrease in pulmonary artery balloon-occluded pressure (from 21.7 +/- 5.8 to 19.8 +/- 6.0 mm Hg, p less than 0.01) without a consistent change in mean arterial pressure (from 79 +/- 8 to 76 +/- 9 mm Hg, difference not significant). Enoximone administration decreased arterial oxygen tension (from 108 +/- 42 to 94 +/- 36 mm Hg, p less than 0.01) and increased venous admixture (from 12.8 +/- 6.5 to 16.0 +/- 8.0%, p less than 0.01). In 8 patients, a second infusion of 0.5 mg.kg-1 immediately thereafter amplified these changes. All patients but one survived the episode of cardiogenic shock and 5 patients left the hospital alive. These results indicate that the addition of enoximone to adrenergic agents in the treatment of cardiogenic shock can markedly increase cardiac output and stroke volume without substantial effects on arterial pressure.
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PMID:Administration of enoximone in cardiogenic shock. 297 Jul 77

Keeping pre-transplant patients alive while waiting for a suitable donor to be found is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 18 transplant candidates with heart failure progression despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. Complete hemodynamic, echocardiographic, and neurohumoral studies were performed before and 24 h after intravenous enoximone infusion. Enoximone infusion increased cardiac index (1.78 +/- 0.45 l/min/qm vs. 3.04 +/- 0.83 l/min/qm; p < 0.001) and stroke volume index (22.33 +/- 9.45 ml/qm vs. 32.28 +/- 7.29 ml/qm; p < 0.05) and decreased wedge pressure (24.1 +/- 11.98 mmHg vs. 17.78 +/- 8.76 mmHg; p < 0.05) and systemic vascular resistance (1700.8 +/- 555.8 dyn x s x cm-5 vs. 952.8 +/- 384.0 dyn x s x cm-5; p < 0.001). Heart rate and mean arterial pressure were unchanged. Left ventricular ejection time (225.1 +/- 26.9 ms vs. 242.2 +/- 25.8 ms; p < 0.05) was increased, whereas other echocardiographic parameters were unchanged (left ventricular end-diastolic dimension, left ventricular end-systolic dimension, fractional shortening, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop of norepinephrine (936.7 +/- 443.2 pg/ml vs. 522.4 +/- 287.6 pg/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-dose enoximone therapy in pre-transplant patients: hemodynamic, echocardiographic, and neurohumoral findings. 809 24

We have studied 28 children (mean age 13.6 months) undergoing elective cardiac surgery involving a myocardial ischaemic time greater than 60 min. Thirteen received phenoxybenzamine 1 mg kg-1 before cardiopulmonary bypass (CPB) and dobutamine 10 micrograms kg-1 min-1 before discontinuation of CPB; 15 received enoximone 0.5 mg kg-1 followed by an infusion of 10 micrograms kg-1 min-1 before discontinuation of CPB. Haemodynamic variables were measured at intervals for 6 h after CPB. Two patients in each group required additional inotropic support with adrenaline. Heart rates, right and left atrial pressures, mean pulmonary artery pressures and systemic and pulmonary vascular resistance indices were similar in the two groups. Mean arterial pressure was significantly greater in those receiving dobutamine (61.3 (SD 7.6) mm Hg) compared with enoximone (56.2 (5.3) mm Hg) (P < 0.05). Differences in cardiac index (thermodilution) (dobutamine group 2.92 (0.62) litre min-1 m-2; enoximone group 2.55 (0.55) litre min-1 m-2) and left ventricular stroke work index (dobutamine group 13.1 (4.7) g m beat-1 m-2; enoximone group 10.4 (2.7) g m beat-1 m-2) were not statistically significant. Enoximone may be used successfully in these patients to assist discontinuation of CPB and maintain an acceptable haemodynamic state in the early postoperative period but, when used alone, conferred no advantage compared with the combination of dobutamine and phenoxybenzamine.
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PMID:Comparison of the haemodynamic effects of dobutamine with enoximone after open heart surgery in small children. 811 May 57

Mitral valve surgery may be complicated by a post-operative low output state requiring inotropic support, and a wide variety of factors may influence the choice of agents used to treat this condition. The authors have examined and compared the haemodynamic effects of the highly specific phosphodiesterase inhibitor enoximone, and the adrenergic agents dobutamine and dopamine in patients undergoing mitral valve surgery. Enoximone, 0.5 mg kg-1 bolus, followed by a continuous infusion of 5 micrograms kg-1 min-1, was compared against dobutamine, 7 micrograms kg-1 min-1, and dopamine, 5 micrograms kg-1 min-1, with the protocol allowing for an increase in the infusion rate by a factor of two if clinical and haemodynamic measurements indicated. All 25 patients receiving enoximone were successfully weaned from cardiopulmonary bypass at the first attempt, with significant increases in cardiac index and stroke index, combined with little or no change in heart rate or pulmonary artery pressures and a highly significant reduction in systemic vascular resistance, and a reduction in mean arterial pressure. Three of the 25 patients receiving dobutamine were withdrawn from the study because of inadequate haemodynamic response, while the remaining 22 patients demonstrated significant increases in heart rate, cardiac index and stroke index, with a reduction in systemic vascular resistance. Nine of the 25 patients receiving dopamine failed to respond adequately, while the remaining 16 demonstrated an increase in heart rate and cardiac index but with little change in stroke index and a modest reduction in systemic vascular resistance. Enoximone has been shown to be a highly effective first-line inotrope in patients following mitral valve surgery with significant advantages over dobutamine and dopamine.
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PMID:Haemodynamic effects and comparison of enoximone, dobutamine and dopamine following mitral valve surgery. 822 51

Keeping pre-transplant patients alive while waiting for a suitable donor is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 35 transplant candidates with progressive heart failure despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. In 18 out of 35 patients complete hemodynamic, echocardiographic, neurohumoral, and Holter-ECG studies were performed before and 24 hours after intravenous enoximone infusion. Patients were then continued on chronic oral therapy of 100 mg twice a day. Enoximone infusion increased the cardiac index (CI) (1.78 +/- 0.45 l/min/m2 vs 3.04 +/- 0.83 l/min/m2; p < 0.001) and stroke volume index (SVI)(22.33 +/- 9.45 ml/m2 vs 32.28 +/- 7.29 ml/m2; p < 0.05) and decreased wedge pressure (PCP)(24.1 +/- 11.98 mmHg vs 17.78 +/- 8.76 mmHg; p < 0.05) while mean arterial pressure (MAP) was unchanged. Left ventricular ejection time (LVET)(225.1 +/- 26.9 ms vs 242.2 +/- 25.8 ms; p < 0.05) was increased whereas other echocardiographic parameters were unchanged (Left ventricular end-diastolic dimension LVEDD, left ventricular end-systolic dimension LVESD, fractional shortening FS, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (Aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop in norepinephrine (936.7 +/- 443.2 pg/ml vs 522.4 +/- 287.6 pg/ml; p < 0.05). Holter-ECG parameters (ventricular premature beats VPB, couplets, ventricular tachycardia VT) were not influenced by enoximone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enoximone therapy as pharmacological bridging to cardiac transplantation. 837 84

We have investigated the circulatory effects of halothane and isoflurane in the presence of the phosphodiesterase inhibitor, enoximone, in 20 patients, ASA class III, aged 40-70 yr, undergoing coronary artery bypass grafting. After induction of anaesthesia (midazolam, fentanyl, etomidate and pancuronium) all patients received enoximone 0.5 mg kg-1, followed, 10 min later, by either halothane 1 MAC (group I; n = 10) or isoflurane 1 MAC (group II; n = 10). Haemodynamic variables were measured and blood samples (arterial and mixed venous) were obtained before (control, t0), 5 (t1) and 10 (t2) min after the injection of enoximone and immediately (t3) and 5 (t4) min after steady state conditions with halothane or isoflurane, as verified by the end-expiratory concentration. Heart rate, mean arterial pressure (MAP), mean pulmonary artery pressure, pulmonary capillary wedge pressure and right atrial pressure were recorded. Cardiac (CI) and stroke volume indices, systemic (SVR) and pulmonary vascular resistance, oxygen availability (QO2), oxygen consumption and oxygen extraction rate were calculated using standard formulae. MAP decreased significantly in both groups after bolus injection of enoximone (group I: 11%; group II: 7%). Under steady state conditions with the volatile anaesthetics, a further significant decrease in MAP was observed (group I: 12%; group II: 12%). Enoximone produced a significant increase in CI (group I: 25%; group II: 27% compared with control). After administration of isoflurane, CI remained essentially unchanged, while halothane decreased CI significantly by 20%. In both groups, SVR decreased significantly after administration of enoximone (group I: 26%; group II: 24%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Haemodynamic changes produced by inhalation anaesthetics in the presence of phosphodiesterase inhibition. 849 3

In 1991 and 1992, we introduced the new phosphodiesterase-III-inhibitor, enoximone, in the treatment of cardiac low-output-syndromes in the early phase after valve replacement or coronary bypass grafting. We introduced enoximone in cases which met the following criteria: cardiac index < or = 2.4 l/min/m2; systolic arterial pressure < or = 90 mmHg; left ventricular filling pressure > or = 20 mmHg despite the use of dopamine (> or = 12 micrograms/kg/ min); epinephrine (> or = 0.12 microgram/kg/min) and glyceroltrinitrate (1 microgram/kg/min). After clarification of preoperative risk factors and postoperative complications, retrospective evaluation of complete haemodynamic monitoring in patients after valve replacement (14 out of 86) and patients after coronary bypass grafting (22 out of 228) led to the following conclusions. Enoximone is of essential importance for the treatment of cardiac low-output at the end of extracorporeal circulation, particularly in cases complicated by preoperative myocardial deterioration. The use of enoximone is especially effective combined with beta-sympathomimetics as a result of elevation of cAMP-levels in two ways: by stimulation of beta-adrenoceptors directly and by inhibition of phosphodiesterase. Cardiac indices early after bypass, compared with measurements taken before bypass, reveal a clear rise indeed caused by increase in heart rate. Only in patients who underwent coronary bypass grafting did we observe a moderate increase in stroke volume indices. The therapeutic principle of using vasodilators--to lower peripheral resistance for improving stroke volume --appears to be effective immediately after extracorporeal circulation only in part. The vasodilating effect of enoximone has to be constantly compensated for by volume supplementation and alpha-mimetic stimulation, especially after valve replacement surgery. In contrast to this, we continued the application of glyceroltrinitrate in about 25% of the cases. Coronary surgery patients tolerated the vasodilating action particularly well; consequently, despite inotropic stimulation to a high degree, these patients showed no additional signs of ischaemia. Based on our therapeutic measures, the therapy led to very good short-term results. However, this therapeutic regime failed in patients suffering from extended myocardial infarction or irreversible pulmonary hypertension.
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PMID:[Enoximone--clinical experiences in heart surgery]. 876 97


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