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 heat failure syndromes are a heterogenous group of conditions. Chronic heart failure exacerbations represent the vast majority of cases. Pathophysiologic mechanisms, such as hypotension with peripheral tissue hypoperfusion, renal function impairment and myocardial ischemia and injury, adversely affect patients' clinical outcome. Classical inotropes, such as beta-agonists (dobutamine, dopamine) and phosphodiesterase inhibitors (milrinone), seem to improve clinical symptoms and hemodynamics of acutely decompensated chronic heat failure patients, but they have been associated with increased long-term mortality. Thus, on the basis of the available evidence, these agents can be used only as a temporary treatment of acute heart failure exacerbations with stringent criteria (ESC AHF guidelines), resistant to intravenous vasodilators and/or diuretics when systolic blood pressure (SBP) is >100 mmHg or as a first-line treatment in patients with worsening of chronic cardiac failure and low SBP (<100 mmHg). The calcium sensitizer levosimendan is a new cardiac enhancer that seems to be more effective than classical inotropes in improving cardiac mechanical efficiency and reducing congestion, without causing cardiomyocyte death or increasing myocardial oxygen uptake. Recent randomized trials showed that levosimendan is not superior to placebo or dobutamine in improving 1- and 6-month mortality, although it caused a greater reduction of neurohormonal response. More data are needed regarding patient selection and the optimum regimen and dosing of levosimendan before this treatment modality become the first line therapy of acutely decompensated chronic heart failure patients.
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PMID:Classical inotropes and new cardiac enhancers. 1748 80

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