Double-blind crossover comparison of enoximone and placebo in patients with congestive heart failure.

Choraria, S.; Taylor, D. J.; Pilcher, J. F.

doi:10.1161/01.cir.76.6.1307

Cited by 30 publications

(4 citation statements)

References 19 publications

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“…In 1987 enoximone was compared to dobutamine and nitroprusside in the management of heart failure and found to be superior to both [69]. This clinical improvement was also demonstrated in other small placebo controlled clinical trials [70–75]. In 1993 the use of enoximone along and in combination with β-blockade was studied and this combination was found to be synergistic [76], the result was later confirmed in a 1998 study by Shakar et al [77].…”

Section: Use Of Inotropic Agents In the Treatment Of Heart Failurementioning

confidence: 93%

Modulation of β-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5

Ho¹,

Yan²,

Iwatsubo³

et al. 2010

Heart Fail Rev

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Despite remarkable advances in therapy, heart failure remains a leading cause of morbidity and mortality. Although enhanced β-adrenergic receptor stimulation is part of normal physiologic adaptation to either the increase in physiologic demand or decrease in cardiac function, chronic β-adrenergic stimulation has been associated with increased mortality and morbidity in both animal models and humans. For example, overexpression of cardiac Gsα or β-adrenergic receptors in transgenic mice results in enhanced cardiac function in young animals, but with prolonged overstimulation of this pathway, cardiomyopathy develops in these mice as they age. Similarly, chronic sympathomimetic amine therapy increases morbidity and mortality in patients with heart failure. Conversely, the use of β-blockade has proven to be of benefit and is currently part of the standard of care for heart failure. It is conceivable that interrupting distal mechanisms in the β-adrenergic receptor-G protein-adenylyl cyclase pathway may also provide targets for future therapeutic modalities for heart failure. Interestingly, there are two major isoforms of adenylyl cyclase (AC) in the heart (type 5 and type 6), which may exert opposite effects on the heart, i.e., cardiac overexpression of AC6 appears to be protective, whereas disruption of type 5 AC prolongs longevity and protects against cardiac stress. The goal of this review is to summarize the paradigm shift in the treatment of heart failure over the past 50 years from administering sympathomimetic amine agonists to administering β-adrenergic receptor antagonists, and to explore the basis for a novel therapy of inhibiting type 5 AC.

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Section: Use Of Inotropic Agents In the Treatment Of Heart Failurementioning

confidence: 93%

Modulation of β-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5

Ho¹,

Yan²,

Iwatsubo³

et al. 2010

Heart Fail Rev

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“…The long-term clinical efficacy of PDE inhibitors is still uncertain, with variable results reported in placebo-controlled trials [71][72][73][74][75][76]. Although recently milrinone was reported to improve exercise parameters, including maximal V~ compared with placebo, this was not accompanied by a significant change in clinical well-being [74].…”

Section: Phosphodiesterase (Pde) Inhibitorsmentioning

confidence: 99%

Vasodilator therapy without converting-enzyme inhibition in congestive heart failure—Usefulness and limitations

Remme

1989

Cardiovasc Drug Ther

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Despite a well-established rationale for pharmacologically induced arterial and venous vasodilatation in congestive heart failure, the clinical usefulness of long-term vasodilator therapy without concomitant converting-enzyme inhibition generally has been disappointing. With the exception of nitrates and, possibly, the combination of nitrates and hydralazine, the use of converting-enzyme inhibitors in many aspects appears preferable in the majority of patients. This article reviews the pathophysiology of inappropriate vasoconstriction in heart failure, the cellular mode of action of the various vasodilators, hemodynamic effects with respect to the peripheral site of action, clinical usefulness and limitations of different vasodilators, and the various determinants of clinical efficacy. Finally, an attempt is made to assess when and how to introduce vasodilator treatment with and without concomitant ACE inhibition.

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“…Re cently several selective phosphodiesteraseinhibiting, non-catecholamine agents have been studied, which are capable of improving cardiac haemodynamics acutely in patients with severe heart failure [1][2][3][4], The positive inotropic and vasodilating properties of one such agent, the selective phosphodiesterase IV inhibitor enoximone [5,6], have been reported to produce a marked short-term and long-term improvement in patients with con gestive heart failure [7][8][9][10][11][12].…”

mentioning

confidence: 99%

Enoximone versus Dopamine in Patients Being Weaned from Cardiopulmonary Bypass

Birnbaum¹,

Preuner²,

Gieseke³

et al. 1990

Cardiology

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The efficacy of acute haemodynamic support with intravenous enoximone (2 × bolus 0.5 mg/kg; infusion 5.0 µg/kg/min) versus dopamine (3.0–4.0 µg/kg/min), over an 18-hour period, was investigated in patients to be weaned from cardiopulmonary bypass (placebo-controlled trial). Under steady-state conditions, enoximone produced a substantial increase in cardiac index (20.6 ± 1.7%), but no change in heart rate. The improvement in cardiac index with time until constant values were reached (6 h) was not directly paralleled by the plasma concentration of enoximone. Pharmacodynamically relevant concentrations were already present after 1 h of infusion (480 ± 68 ng/ml) and comparable with the value determined after 6 h (442 ± 37 ng/ml). After 18 h of infusion, plasma concentration had reached 742 ± 47 ng/ml without a further improvement in cardiac function. The augmentation of stroke volume index (23.3 ± 2.5%) occurred concomitantly with a decrease in systemic vascular resistance (-23.1 ± 0.6%), obviously due to a decrease in diastolic arterial pressure (-12.0 ± 3.8%). The pulmonary capillary wedge pressure remained unaffected. There was only a slight decrease in pulmonary vascular resistance (-9.3 ± 3.2%). During both enoximone infusion and dopamine infusion, right atrial pressure increased (10.0 ± 3.1 and 9.0 ± 1.8%, respectively), in contrast to the untreated control group. This is contradictory to the drugs’ described effect in patients suffering from congestive heart failure. At a concentration which would not normally cause cardiac acceleration, dopamine provided minor haemodynamic support in the period after cardiopulmonary bypass. A small increase in cardiac index (5.9 ± 2.2%) was accompanied by a slight decrease in systemic (-4.2 ± 3.2%) and pulmonary ( 11.4 ± 2.4%) vascular resistances. The results indicate that enoximone produced beneficial haemodynamic effects in the period following cardiopulmonary bypass. Both inotropic and vasodilatory effects appeared to be manageable.

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Double-blind crossover comparison of enoximone and placebo in patients with congestive heart failure.

Cited by 30 publications

References 19 publications

Modulation of β-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5

Modulation of β-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5

Vasodilator therapy without converting-enzyme inhibition in congestive heart failure—Usefulness and limitations

Enoximone versus Dopamine in Patients Being Weaned from Cardiopulmonary Bypass

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