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

Recent advances in our knowledge of heart failure have shown that both a central and a peripheral factor are involved in this syndrome. Therefore, the ideal drug should combine the properties of a positive inotropic agent with those of a peripheral vasodilator; many drugs recently introduced into clinical practice have been shown to present both of these features, and the term "inodilators" has been used to characterize them. Inodilators can be further classified on the basis of their mechanism of action, i.e., phosphodiesterase inhibitors, and sympathomimetic and dopaminergic drugs. Phosphodiesterase inhibitors include bipyridine, imidazolone, and benzimidazole derivatives, which present potent inotropic and vasodilatatory actions. Despite their favorable acute effects, long-term studies have often yielded controversial, and sometimes disappointing, results as their chronic administration seems often to be associated with untoward effects and, above all, a poor prognosis. Sympathomimetic agonists act by stimulation of beta-receptors, with a consequent increase of myocardial contractility and peripheral vasodilation. Differently from the parenteral drugs (e.g., dobutamine), the oral agents present many important shortcomings including central nervous system effects, increased myocardial oxygen consumption, tachyarrhythmias, and, above all, development of tolerance during chronic administration. Dopaminergic drugs possess a unique pharmacologic profile since they add to the adrenergic stimulation their selective action on dopaminergic receptors. Dopamine is still one of the most useful drugs for the treatment of acute heart failure; the two oral drugs that more closely resemble its actions are levodopa and ibopamine. The administration of levodopa to patients with heart failure can induce a significant hemodynamic improvement that is maintained during chronic therapy. Ibopamine has been widely shown to cause a significant hemodynamic improvement in patients with heart failure. Its effects can be ascribed to a moderate increase of myocardial contractility accompanied by peripheral and renal vasodilatatory actions. This drug can also counteract some of the neurohumoral mechanisms (e.g., sympathetic stimulation and aldosterone secretion) that are activated in heart failure. These features can explain the favorable results that have also been recently obtained after the chronic administration of ibopamine.
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PMID:Clinical pharmacology of inodilators. 248 42

The pathophysiological understanding and management of acute and chronic heart failure have changed dramatically in the past decade. Since the early 1980s, a major effort has been made to develop nonglycosidic, noncatecholamine agents that combine inotropic and vasodilating properties, in order to treat myocardial dysfunction unresponsive to current therapy. Within this context, increasing attention has been paid to the role of intracellular cyclic adenosine monophosphate (cAMP) in myocardial contractility. The pharmacologic use of catecholamines to stimulate beta-receptors activates adenylate cyclase, which in turn leads to an increase in intracellular levels of cAMP. In addition, phosphodiesterase 3 (PDE 3) inhibition may prevent the degradation of cAMP, thus maintaining high intracellular levels of the substance. Intravenous amrinone has been shown clinically to improve hemodynamic status remarkably in the patient experiencing a low cardiac output syndrome, by increasing CO while decreasing filling pressures and pulmonary arterial pressures, without increasing myocardial O2 demand. This report will review several studies of different types of patients and explain the effects of amrinone alone and in combination with the more traditionally used catecholamines. It must be stressed that amrinone, in spite of its dual action of inotropy and vasodilation, should not be considered a rival to catecholamines but rather an enhancer of them, which clinicians should consider using in the early stages of therapy in many different settings.
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PMID:Historical perspectives and update of amrinone. 252 Oct 46

A bipyridine derivative, amrinone is a noncatecholamine, nonglycoside alternative in the treatment of perioperative myocardial dysfunction. A type-3 phosphodiesterase enzyme inhibitor, amrinone combines positive inotropic support with systemic and pulmonary vasodilation. In patients with heart failure undergoing cardiac or noncardiac surgery, the absence of tachycardia and dysrhythmias is of particular clinical benefit. In these patients, amrinone's ability to augment cardiac performance without increasing heart rate or myocardial oxygen consumption offers significant clinical advantages during the perioperative period.
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PMID:Clinical applications of amrinone. 252 Oct 48

In the treatment of acute heart failure, conventional therapy with epinephrine, norepinephrine, dopamine, and dobutamine may be used effectively to treat inotropic abnormalities. However, the addition of a vasodilator to catecholamine therapy may be needed to help improve lusitropic function. Because it seems to exert positive inotropic and lusitropic effects, the phosphodiesterase inhibitor amrinone may be a valuable addition to the anesthesiologist's armamentarium for the treatment of acute heart failure. When used as adjunctive therapy with catecholamines, amrinone has been shown to exert a significant additive and synergistic effect. Amrinone may also be the inotrope of choice in patients who are refractory to therapy with conventional inotropes, due to its positive inotropic and lusitropic effects, combined with its vasodilating effects. Because of its broad pharmacodynamic spectrum, amrinone may effectively control all of the major elements involved in myocardial performance--preload, afterload, contractility, and heart rate.
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PMID:Amrinone: is it the inotrope of choice? 252 Oct 51

The existing management of severe chronic congestive heart failure carries a dismal prognosis. Mortality over 6 months is 50% by some estimates. This fact, coupled with increasing concern for the safety and efficacy of the digitalis glycosides, has stimulated an intense search for new oral cardiotonic agents suitable for chronic administration. Despite the ability of many phosphodiesterase inhibiting agents to affect profound hemodynamic improvements acutely after oral or intravenous administration, none of the four agents here reviewed in 30 clinical trials has been adequately proven to provide benefit over conventional long-term therapy of severe heart failure. The four drugs to have undergone long-term clinical trials are amrinone, milrinone, enoximone (MDL 17043), and piroximone (MDL 19,025). For amrinone, inefficacy was revealed through carefully designed, placebo-controlled studies despite initial enthusiasm generated by open uncontrolled trials. Enoximone has suffered rapid attenuation of its hemodynamic effectiveness in most studies, and piroximone failed in its only long-term trial. Therefore, final judgment on most of these agents must await completion of controlled clinical trials, and any initial optimism stimulated by the current uncontrolled studies should be met with reservation.
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PMID:Long-term oral therapy of congestive heart failure with phosphodiesterase inhibitors. 252 82

Twenty patients with moderately severe congestive heart failure were randomized to chronic enoximone (n = 10) or placebo (n = 10) therapy in a double-blind manner and serially evaluated over a 16-week-period. The purpose of the study was to determine if the addition of standard doses (1 and 2 mg/kg) of this new phosphodiesterase inhibitor to conventional therapy (digitalis and diuretics) would alter the clinical and laboratory course of this patient population. Except for a transient improvement in the quality of life score, none of the symptomatology indicators were significantly affected by enoximone. Similarly, maximal exercise capacity was not altered. Enoximone did elicit a statistically significant augmentation of echocardiographic, radionuclide angiographic, and systolic time interval parameters of left ventricular function. These enoximone-induced effects were accompanied by a significant increase (7% to 11%) in resting heart rate. Enoximone is capable of improving ventricular function when added to digitalis-diuretic therapy in moderately severe congestive heart failure. While individual patients may benefit from enoximone, the ability of standard doses of this agent to improve symptoms and exercise capacity over a 16-week period appears somewhat limited in a moderately severe heart failure population as a whole. Furthermore, a disparity between improvement in ventricular function parameters and changes in clinical status and exercise performance is apparent in this heart failure population.
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PMID:Disparity between improvement in left ventricular function and changes in clinical status and exercise capacity during chronic enoximone therapy. 252 34

The new phosphodiesterase-III inhibitor (PDI) enoximone is a non-catecholamine, non-glycoside cardiotonic agent with concomitant vasodilating properties. It has proved beneficial in patients with severe chronic heart failure. The influence of enoximone i.v. on hemodynamics was investigated during cardiac surgery under various conditions. METHODS. A randomized series of 60 patients undergoing elective aorto-coronary bypass grafting were studied. The hemodynamic effects of 0.5 mg/kg enoximone given i.v. as a bolus (30 s) were investigated before anesthesia (n = 10), during anesthesia (n = 10), and during extracorporeal circulation (ECC, n = 10) and compared with those observed in corresponding control groups (n = 10 in each control) of patients who had received saline solution as placebo. Anesthesia was maintained with weight-dependent dosages of fentanyl, midazolam and pancuronium bromide. All patients were invasively monitored by means of a pulmonary artery catheter. Additionally, left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP) and dp/dtmax were measured before the initiation of ECC. During ECC direct vascular effects were investigated with measurement of perfusion pressure and the volume of the oxygenator. RESULTS. Before the induction of anesthesia no significant change in MAP and HR could be observed, whereas CI increased (+20%) and TSR decreased (-24%) significantly. During anesthesia, the injection of enoximone was followed by a significant decrease in MAP only in the 1st min (-17%); baseline level was reached again after 6 min; and HR was slightly increased (+8%). TSR (-31%) and LVEDP (-38%) decreased, whereas CI (+17%) and dp/dtmax (+45%) were increased significantly. During ECC perfusion pressure (-37%) and the volume of the oxygenator (-17%) were significantly decreased, demonstrating direct vasodilating effects on both the arteries and the vein. CONCLUSION. Arterial and venous vasodilation with an increase in myocardial performance (dp/dtmax) resulting in an increase in CI were the predominant hemodynamic effects of enoximone i.v. No arrhythmogenic effects or interactions with the anesthetics used were observed in this study.
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PMID:[Hemodynamic effects of the new phosphodiesterase inhibitor enoximone in heart surgery patients]. 252 51

In the present study, the safety and efficacy of the combined administration of intravenous nitroprusside and oral enoximone, an experimental compound with phosphodiesterase inhibitory properties, were evaluated. Ten patients with unstable chronic heart failure maintained on digitalis and diuretics were selected to receive enoximone because of their poor response to intravenous nitroprusside. For a mean peak dose of 115 micrograms min-1 nitroprusside, cardiac index increased from 1.8 +/- 0.4 to 2.0 +/- 0.4 l min-1 m-2, while pulmonary artery diastolic pressure and mean right atrial pressure decreased from 29 +/- 6 to 24 +/- 5 and from 15 +/- 6 to 11 +/- 3 mmHg respectively; mean arterial pressure and heart rate were unchanged. The addition of 1.6 mg kg-1 oral enoximone t.i.d. to nitroprusside resulted in a substantial improvement of cardiac function: cardiac index increased further to 2.8 +/- 0.5 l min-1 m-2 (P less than 0.001), pulmonary artery diastolic pressure and right atrial pressure decreased to 18 +/- 5 and 7 +/- 3 mmHg (P less than 0.01), respectively, while mean arterial pressure rose from 90 +/- 11 mmHg to 95 +/- 0 mmHg (P less than 0.05); heart rate was unchanged. The salutary haemodynamic response to combined nitroprusside-enoximone therapy persisted for more than 32 h, and cardiac performance remained improved on enoximone for a further 8 h despite the discontinuation of nitroprusside. No serious side-effects or changes in the arrhythmia profile were observed. The addition of oral enoximone to nitroprusside has beneficial haemodynamic effects in unstable chronic heart failure.
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PMID:Additive effects of enoximone and nitroprusside in unstable chronic heart failure. 252 55

The effects of enoximone, a new cyclic adenosine monophosphate phosphodiesterase inhibitor, were compared with those of captopril in a double-blind study in a group of 10 patients with severe heart failure. Four weeks treatment with enoximone improved symptom-limited exercise tolerance from a mean value of 11.33 to 13.36 minutes (P less than 0.05) and 4 weeks of captopril treatment from 11.01 to 13.92 minutes (P less than 0.05). Four of the patients had a greater exercise tolerance taking enoximone, the remaining 6 while taking captopril. Both drugs reduced perceived exertion during submaximal exercise. Minute ventilation measured at rest and during submaximal exercise was also reduced by both drugs. Resting and post exercise calf blood flow was increased to a similar extent with captopril (P less than 0.03) and enoximone (P less than 0.005). There was no difference in calf blood flow and calf vascular resistance between the drugs suggesting that the peripheral haemodynamic effects of enoximone are due to peripheral vasodilatation. Enoximone is a useful drug for the treatment of patients with severe heart failure.
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PMID:Comparison of the effects of captopril and enoximone in patients with severe heart failure: a placebo controlled double-blind study. 252 29

Phosphodiesterase inhibitors have vasodilating and positive inotropic properties, and these compounds may have energy saving effects due to vasodilation and energy consuming effects due to inotropism. In order to differentiate between the effects, it is necessary to relate myocardial oxygen consumption to its hemodynamic determinants. Myocardial oxygen consumption per beat was related to the following parameters: dp/dtmax, mean velocity of fiber shortening, pressure-volume work, peak developed wall stress, and stress-time integral. The best linear relationship was found between myocardial oxygen consumption per beat and the corresponding stress-time integral (r = 0.71; p less than 0.001) in patients with idiopathic dilative cardiomyopathy. Using i.v. nitroprusside as a pure vasodilator, myocardial oxygen consumption per beat and stress-time integral decreased along this established relationship. In contrast, the phosphodiesterase inhibitor enoximone given intravenously decreased the stress-time integral significantly more than the myocardial oxygen consumption per beat. We conclude from these data that phosphodiesterase inhibitors possess vasodilating properties which reduce the myocardial oxygen demand. In addition, they do have positive inotropic effects which increase the myocardial oxygen demand. Myocardial oxygen consumption always reflects the sum of both effects. The balance between the energy saving and the energy consuming effects may determine the efficacy of phosphodiesterase inhibitors, especially in the long-term treatment of chronic heart failure.
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PMID:Separation between vasodilation and positive inotropism by assessment of myocardial energetics in patients with dilated cardiomyopathy. 253 Sep 75


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