Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute heart failure following cardiac surgery in extracorporeal circulation (EC) still poses a formidable problem requiring intensive pharmacological therapy and, often, also mechanical support. Preoperatively reduced left ventricular (LV) function raises the risk for the development of this complication. In their pilot study, the authors evaluated the haemodynamic effects of enoximone, a selective phosphodiesterase III inhibitor, administered at a dose of 1 mg/kg b.w. to 15 patients with a preoperative LV ejection fraction < or = 35% 15 minutes before weaning from EC after an elective myocardial revascularization procedure. All patients were weaned from EC at first attempt without any problems and left the operating theatre in good condition. Enoximone administration led, in the monitored period (45 minutes after administration), to statistically significant increases in cardiac index (+68%; p < 0.01), oxygen supply (+75%; p < 0.01) and oxygen saturation in mixed venous blood (+10%; p < 0.1) and statistically significant decreases in pulmonary and systemic vascular resistance indexes (-52% and -48%, respectively; p < 0.001) and in oxygen extraction (-31%; p < 0.001). These changes were associated with decreases in central venous, mean pulmonary artery, and pulmonary capillary wedge pressure (n.s.). No serious side effects were seen, and the authors conclude enoximone can be the drug of first choice in high-risk patients following heart surgery in EC and requiring inotropic support.
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PMID:[Hemodynamic effects of enoximone in patients with low left ventricular ejection fraction in surgery for ischemic heart disease]. 825 78

Low heart stroke volume syndrome is clinically manifested with hypoperfusion of all body systems. Inotropic or mechanical support is applied. Acute heart failure is one of the most important complications after open heart surgery. Catecholamines have been up to non considered as a therapy of choice for the acute heart failure. Effectiveness of catecholamines could be limited with some side effects. Phosphodiesterase inhibitors promise a new therapeutic approach. PDE III primary act through phosphodiesterase inhibition which leads to a rise of aAPM levels. Thus they show positive inotropic and lusitropic effects, which could be monitored by occlusive pulmonary capillary pressure values. Amrinone is obviously superior to inotropic catecholamines.
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PMID:[Hemodynamic effects of amrinone, dobutamine and dopamine in the cardiac low output syndrome following open-heart surgery]. 864 47

Acute heart failure syndromes (AHFS) are a growing health problem in Western Countries. Standard treatment includes vasodilators and diuretics, however, the subgroup of patients with AHFS and low cardiac output state represents a special therapeutic challenge that is complicated by high in-hospital and post-discharge mortality and by requiring additional i. v. inotropic support. The current inotropes in use are adrenoreceptor agonists (dopamine, dobutamine, norepinephrine, epinephrine), phosphodiesterase III inhibitors (milrinone, enoximone), and Ca2+ sensitizers (levosimendane). While most inotropes yield short-term haemodynamic improvements, they are associated with increased myocardial oxygen consumption, (supra-) ventricular arrhythmias and possibly increased post-discharge mortality. This review highlights current inotropes used in the treatment of AHFS and introduces new drug developments including myosin activators and Na+/K+ ATPase inhibitors.
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PMID:[Rational use of catecholamines and inotropes]. 1792 14

Acute heart failure represents a major public health problem due to its high prevalence, high rates of mortality and readmissions and significant healthcare costs. Patients with AHF and low cardiac output represent a small subgroup of patients with very high mortality rates that require inotropic support to improve cardiac systolic function. Classical inotropic agents, such as beta1-adrenergic agonists (dobutamine, dopamine) and phosphodiesterase III inhibitors (milrinone, enoximone) improve symptoms and hemodynamics by increasing free intracellular Ca(2+) levels, but also increase myocardial O(2) demands and exert arrhythmogenic effects. These actions explain why these drugs increase both short- and long-term mortality, particularly in patients with AHF and coronary artery disease. Thus, we need new inotropic agents that do not increase cytosolic Ca(2+) or myocardial oxygen demands or produce arrhythmogenesis for the treatment of high-risk patients with acute heart failure and low cardiac output. This review describes three new classes of investigational agents: levosimendan, a calcium sensitizer and potassium channel opener, istaroxime, the first new luso-inotropic agent and cardiac myosin activators.
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PMID:Investigational positive inotropic agents for acute heart failure. 1953 58

Acute heart failure (AHF) is a major cause of hospitalizations. Severe dyspnea, pulmonary congestion and low cardiac output with peripheral vasoconstriction and renal hypoperfusion is a main form of clinical presentation. Most patients with acute worsening have a pre-existing decompensated chronic heart failure (ADCHF), but AHF may also occur as a first manifestation of a previously unknown heart disease. Myocardial ischemia, cardiac arrhythmias, non-compliance with medication and infections are frequent precipitating factors. Management of AHF depends on the underlying heart disease and cause of decompensation. In patients with ADCHF vasodilators and iv diuretics are first-line drugs for rapid reduction of dyspnea and congestion. In patients with signs of low cardiac output and oliguria, inotropic agents are also often administered to prevent further deterioration. Beta-adrenergic agents and phosphodiesterase inhibitors correct the hemodynamic disturbance, but may also induce arrhythmias and worsen myocardial ischemia. Inotropic therapy therefore remains controversial. A novel class of drugs, the calcium sensitizers, represent a new therapeutic option. Levosimendan was shown to improve myocardial contractility without increasing oxygen requirements and to produce peripheral and coronary vasodilation. Its therapeutic effects and tolerance have been tested in several trials. The present review focuses on the clinical pharmacology and therapeutic utility of levosimendan in patients with ADCHF.
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PMID:Newer treatments for decompensated heart failure: focus on levosimendan. 1992 Sep 23

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.
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PMID:Treatments targeting inotropy. 3029 7