Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

46-year-old male patient was born in Niigata Prefecture and thereafter lived in Tokyo. In late January 1985, he noticed swelling of the bilateral inguinal lymph-nodes followed by fever and lumbago. In February, he consulted a local doctor and hepatosplenomegaly, marked leukocytosis and renal dysfunction were pointed out and he was referred to our hospital on February 22nd. The clinical laboratory data on admission were as follows; WBC 23,200/microliter, serum-Ca 18.4 mg/dl, BUN 85.3 mg/dl, creatinine 5.4 mg/dl, antibody to ATLV x160. ATL was diagnosed by biopsy of lymph nodes and examinations of peripheral blood and bone marrow hemogram. Remission was achieved in March by the treatment with adriacin. Renal failure and hypercalcemia also improved. However his respiratory dysfunction gradually worsened. The chest radiographies++ showed pulmonary edema, although there was no clinical evidence of heart failure. When his condition became stable, TBLB was performed and revealed extensive deposition of calcium along alveolar septae, suggesting that pulmonary edema was induced by the metastatic calcification of the lung. After the second treatment for ATL, he died of pneumonia. The autopsy showed calcium deposition not only in the lung but in pyramids of the kidney and in sub-serous layer of the small intestine. There was no tumor cell invasion into the bone or parathyroid gland. High urinary c-AMP together with normal levels of PTH suggested that the hypercalcemia in this case was induced by PTH-related protein. It was concluded that careful treatment for hypercalcemia is important as regards the occurrence of pulmonary edema.
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PMID:[An autopsy case of adult T-cell leukemia complicated with metastatic calcification of the lung]. 204 Dec 50

Theoretically, there are two reasons for using the association of dobutamine and enoximone in patients with acute cardiac failure; the powerful vasodilator effect of enoximone and the different biochemical actions of the two drugs on the myocardial fibre affecting the production (dobutamine) or the degradation (enoximone) of cyclic AMP. The combined effects of beta adrenergic agonists and phosphodiesterase III inhibitors in vitro and in vivo have been previously reported. An increased contractile response to dobutamine has been demonstrated with enoximone on isolated human ventricle obtained during cardiac transplantation. We confirmed the additive effect of dobutamine (5 to 10 micrograms/kg/min) and enoximone (1 mg/kg/bolus IV) in 8 patients with acute cardiac failure with each molecule used alone. Mild changes in heart rate (+19 bpm) and in systolic blood pressure (-3 mmHg) were observed simultaneously. The absence of an increase in SvO2 compared to the use of each molecule in monotherapy is probably related to a tendency to increase myocardial oxygen consumption which may be potentially deleterious in terms of gas exchange. Having demonstrated the additive effects of the association of dobutamine and enoximone, there is probably a place for this therapeutic association in the management of acute cardiac failure. However, the potential risk of inducing an atrial and/or ventricular tachyarrhythmia and the consequences of lowering ventricular filling pressures and systemic vascular resistances should be born in mind; when using this therapeutic association, the authors suggest starting treatment with low doses of dobutamine (5/kg/min) and enoximone (0.5 - 1 mg/kg) with haemodynamic control and steadily increasing the doses, depending on the results obtained.
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PMID:[Role of the enoximone-dobutamine combination in the treatment of congestive cardiac insufficiency]. 214 32

Enoximone belongs to a new class of noncatecholamine-positive inotropes, which selectively inhibit phosphodiesterase type III and increase cyclic AMP (cAMP). This study was performed in 30 coronary artery surgery patients with impaired myocardial function (ejection fraction [EF] less than 50%). The study's two purposes were to investigate the hemodynamic effects of enoximone, 0.5 mg/kg, administered following induction of anesthesia (phase I), and to assess whether enoximone can potentiate the actions of sympathomimetic agents during weaning from cardiopulmonary bypass (CPB) (phase II). Starting with already reduced hemodynamics, induction of anesthesia led to a further deterioration of blood pressure and cardiac output (CO). Administration of enoximone produced a significant increase in cardiac index (CI) (+47%), whereas pulmonary capillary wedge pressure (PCWP) (-37%), pulmonary artery pressure (PAP) (-17%), and systemic vascular resistance (SVR) (-17%) were significantly reduced. Heart rate (HR) was not increased, and no dysrhythmias occurred during the investigation. The hemodynamic effects were maintained for 30 minutes until the start of the operation. In phase II, where weaning from CPB was not possible without pharmacological support, either enoximone (0.5 mg/kg) + epinephrine (0.1 micrograms/kg/min) or only epinephrine (same dosage) was randomly selected. Weaning was successful in both groups, but the combined therapy produced a larger increase in cl and a more pronounced decrease of the elevated filling pressure (PCWP). PAP was not changed in the combined therapy group, but increased in the patients receiving epinephrine alone. It is concluded that enoximone has beneficial hemodynamic effects in the perioperative period, and that potentiation of the effects of epinephrine in severe heart failure may be one of the drug's most useful features.
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PMID:Enoximone treatment of impaired myocardial function during cardiac surgery: combined effects with epinephrine. 215 89

Calcium ions are important in many aspects of normal cardiac function as well as in the response to certain pathologic states. The contribution that myocardial calcium influx makes to the cardiac action potential and the pharmacologic efficacy of compounds designated as calcium channel blockers is examined with respect to current knowledge regarding the structure and characteristics of cardiac sarcolemmal calcium channels. Once intracellular, calcium provides the link between cardiac electrical activity and actual mechanical shortening of cardiomyocytes through a complex interaction of regulatory and structural contractile proteins. This is followed by calcium clearance from the cytosol; the mechanisms by which this occurs are manipulated by drugs such as the digitalis glycosides to enhance myocardial contractility. The importance of intracellular 'second messengers' (eg, cyclic AMP) in constituting a final common pathway for the effects of certain cardiotonic agents is defined. The significance of abnormal calcium homeostasis under conditions of heart failure, myocardial infarction, ventricular fibrillation and cardiomyopathy is examined. The role of calcium in the mediation of myocardial damage under conditions of ischemia and secondary to a phenomenon known as 'the calcium paradox' is discussed. The finding that neonatal hearts are more vulnerable to ischemic contracture than adult hearts may be partially explained by differences between neonatal and adult myocardial calcium handling. Understanding of the interactions that exist between the calcium ion and the cardiomyocyte requires a sound knowledge of this essential partnership by both the physiologist and the practising physician.
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PMID:Calcium and the heart: an essential partnership. 217 38

Low cardiac output in acute heart failure can result in a functional impairment of organs, when tissue hypoxia occurs and cardiogenic shock develops. To restore cardiac output, various forms of therapy can be considered. Fluid replacement is sometimes beneficial in acute situations where oedema can reduce effective plasma volume. Vasodilators are often contra-indicated in shock, when arterial pressure is usually low. Inotropic therapy consists primarily of the administration of adrenergic agents. Dopamine and noradrenaline can be indicated in severe hypotension, to maintain coronary perfusion. Dobutamine is the catecholamine of choice to increase myocardial contractility. However, decreased responsiveness of the myocardial receptors to adrenergic stimulation rapidly becomes an important limitation. Phosphodiesterase inhibitors represent an interesting option to increase contractility, also by increasing cyclic AMP levels in the myocardium. In this respect, the combination of phosphodiesterase inhibitors with adrenergic agents is attractive. The additional vasodilatory properties of these agents can contribute to the increase in cardiac output with limited risk of further reduction in arterial pressure. In 13 patients with cardiogenic shock persisting despite the use of adrenergic agents, the addition of enoximone, 0.5 mg/kg, resulted in significant increases in cardiac index and stroke volume index and a significant decrease in pulmonary artery balloon occlusion pressure without consistent change in mean arterial pressure. In 8 patients, a second infusion of 0.5 g/kg amplified these effects. All but one of these patients survived the episode of cardiogenic shock, and 5 patients were discharged alive. In some cases, even lower doses of enoximone resulted in dramatic increases in cardiac output and oxygen transport in patients already treated with dobutamine with limited success.
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PMID:The role of enoximone in the treatment of cardiogenic shock. 217 30

The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure.
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PMID:Inotropic effects of angiotensin II on human cardiac muscle in vitro. 224 22

Cyclic nucleotide phosphodiesterase (PDE) isozymes isolated by DEAE-Sephacel or Mono-Q High Performance Liquid Chromatography from cardiac left ventricular tissue of normal subjects and patients with end-stage heart failure have been compared. With both separation techniques, four major peaks of PDE activity were evident in the soluble fractions; only one peak of activity was present in particulate fractions. The specific activity of the particulate PDE from myopathics was approximately 30-50% of that of normals while the specific activity of a soluble form of this PDE (peak IIIa) was reduced by 30% in myopathics. No differences in comparison of the other peaks of PDE activity were evident. The particulate PDE isozyme has a low Km for cAMP (0.27-0.29 microM), is inhibited by cGMP (60-80% at 1 microM), is sensitive to inhibition by submicromolar concentrations of CI-930 but not rolipram, and is competitively inhibited by milrinone (Kj = 0.3 microM). The first soluble peak of PDE activity hydrolyzes both cAMP and cGMP and is stimulated by calmodulin while cyclic AMP hydrolysis by peak II PDE is stimulated by cGMP. The other soluble peak III fractions (IIIa and IIIb) hydrolyze cAMP; peak IIIa is inhibited by cGMP or by CI-930 and milrinone, whereas peak IIIb is also inhibited by rolipram when the cardiotonic sensitive PDE is inhibited by CI-930. Thus, cardiotonic-sensitive, cGMP-inhibitable, low Km cAMP PDE is present in both the soluble and particulate fractions of human cardiac left ventricular muscle of hearts from normal and cardiomyopathic subjects while the rolipram-sensitive PDE is present in the soluble fraction. The major differences in PDE activity of myopathic relative to normal left ventricular tissue are a reduced specific activity and Vmax of particulate PDE and one of the soluble peak III PDEs.
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PMID:Cellular distribution and pharmacological sensitivity of low Km cyclic nucleotide phosphodiesterase isozymes in human cardiac muscle from normal and cardiomyopathic subjects. 228 32

In hypertensive cardiac hypertrophy, inotropic responsiveness of alpha and beta adrenergic stimuli is reduced. We have previously shown that hearts from two-kidney, one-clip renal hypertensive rats (RHR) have increased beta-adrenergic receptor density and a defect in the guanine nucleotide regulatory protein, leading to decreased adenylate cyclase activity. In spontaneously hypertensive rats (SHR), beta-receptor density was decreased with no change in adenylate cyclase. In these present experiments, we have shown that the alpha 1-adrenergic receptor changes are in the opposite direction, decreasing in RHR and increasing in SHR. All these changes are reversible within 4 weeks following removal of the clipped kidney in RHR, at which time blood pressure and heart weight have also returned towards normal. Further studies on the excitation-contraction pathway have indicated that c-AMP-stimulated protein kinase is decreased in SHR with no changes seen in RHR. Subcutaneous infusion of epinephrine leads to some increase of cardiac mass associated with decreased beta-adrenergic receptors element and decreased adenylate cyclase activity. However, following angiotensin II infusion, even though hypertrophy is more pronounced, no changes in receptors or cyclase are detected. We conclude that different models of hypertensive cardiac hypertrophy associated with different biochemical defects in the adrenergic excitation response pathway, and that if some of these changes become irreversible, further cardiac deterioration and even heart failure may ensue.
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PMID:Excitation-contraction coupling in hypertrophied myocardium. 241 74

Inotropic stimulation of the failing heart, although a logical adjunct in short-term efforts to maintain circulatory function in patients with heart failure, has several potentially deleterious effects that may limit its usefulness in long-term therapy for patients with congestive heart failure. These deleterious effects include cell damage caused by an increased rate of energy expenditure, exacerbation of relaxation abnormalities, and potential arrhythmogenic side effects that may result from increased cytosolic Ca++ and cyclic AMP concentrations in the inotropically stimulated myocardium. Recognition of these possible side effects should allow the therapeutic benefits of this approach to long-term therapy to be evaluated in carefully controlled clinical trials.
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PMID:Potential deleterious effects of inotropic agents in the therapy of chronic heart failure. 241 47

We studied the effects of different classes of inotropic drugs on human working myocardium in vitro that was isolated from the hearts of patients with end-stage heart failure, and compared the responses to these drugs with those noted in muscles from nonfailing control hearts. Although peak isometric force generated in response to increased extracellular calcium reached control levels in the muscles from patients with heart failure, the time course of contraction and rate of relaxation were greatly prolonged. The inotropic effectiveness of the beta-adrenergic agonist isoproterenol and the phosphodiesterase inhibitors milrinone, caffeine, and isobutylmethylxanthine was markedly reduced in muscles from the patients with heart failure. In contrast, the effectiveness of inotropic stimulation with acetylstrophanthidin and the adenylate cyclase activator forskolin was preserved. After a minimally effective dose of forskolin was given to elevate intracellular cyclic AMP levels, the inotropic responses of muscles from the failing hearts to phosphodiesterase inhibitors were markedly potentiated. These data indicate that an abnormality in cyclic AMP production may be a fundamental defect present in patients with end-stage heart failure that can markedly diminish the effectiveness of agents that depend on generation of this nucleotide for production of a positive inotropic effect.
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PMID:Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure. 243 73


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