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)

1. The signal transduction process mediated by cyclic AMP that leads to the characteristic positive inotropic effect (PIE) in association with a positive lusitropic effect (acceleration of rate of twitch relaxation) has been well established. Relationships between accumulation of cyclic AMP, changes in intracellular Ca2+ transients and the PIE differ, however, depending on the mechanism of particular drugs that affect different steps in the metabolism of cyclic AMP. Selective partial agonists of beta 1-adrenoceptors and inhibitors of phosphodiesterase (PDE) III cause the accumulation of less cyclic AMP for a given PIE than does isoproterenol. In addition, in aequorin-microinjected canine ventricular muscle, selective inhibitors of PDE III, OPC 18790 and Org 9731, produced smaller decreases in the responsiveness of myofilaments to Ca2+ ions than isoproterenol, while a partial agonist of beta 1-adrenoceptors, denopamine, elicits a decrease in Ca2+ responsiveness of the same extent as does isoproterenol. 2. Activation of myocardial alpha 1-adrenoceptors, as well as stimulation of receptors for endothelin and angiotensin II, which accelerates hydrolysis of phosphoinositide (PI) to result in production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) are associated with very similar inotropic regulation: (1) the dependence on the species of animals of induction of the PIE; (2) an excellent correlation between the extent of acceleration of hydrolysis of PI and the PIE; (3) isometric contraction curves associated with a negative lusitropic effect; (4) the PIE associated with increases in myofibrillar responsiveness to Ca2+ ions; and (5) the selective inhibition of the PIE by an activator of protein kinase C (PKC), phorbol 12,13-dibutyrate (PDBu), with little effect on the PIE of isoproterenol and Bay k 8644. 3. A novel class of cardiotonic agents, namely, Ca2+ sensitizers such as EMD 53998 and Org 30029, act on the Ca(2+)-binding site of troponin C, increasing the affinity of these sites for Ca2+ ions, or at the actin-myosin interface to facilitate the cycling of cross-bridges. These agents produce a PIE with little change or decrease in Ca2+ transients and may bring about a significant breakthrough in the development of drugs for reversal of myocardial failure in the treatment of congestive heart failure.
Gen Pharmacol 1995 Jan
PMID:The effects of various drugs on the myocardial inotropic response. 771 48

1. The effects of veratridine, BDF 9148 and lignocaine on the action potentials and contractile force of the electrically-driven rat right ventricle have been determined. 2. Veratridine at 10(-7)-10(-6) M and BDF 9148 at 10(-7)-10(-5) M had no effect on the threshold potential or amplitude but prolonged the ventricular action potentials. 3. In contractility studies, veratridine at 10(-7)-10(-6) M augmented the cardiac stimulation responses and the augmenting effects with 3 x 10(-7) and 10(-6) M were greater at 2 than 4 Hz. In the presence of veratridine at 3 x 10(-6) M, the ventricle would not pace. 4. BDF 9148 at 10(-7)-10(-5) M augmented the cardiac stimulation responses and the augmenting effects with 10(-7) and 3 x 10(-7) M were greater at 2 than 4 Hz and the effect was maximal at 3 x 10(-7) M and submaximal at 10(-5) M. The effects of BDF 9148 at 10(-5) were not readily reversible. 5. Lignocaine at 10(-4) M had no effect on the ventricular action potential duration but decreased the threshold potential and amplitude and also reduced the cardiac stimulation force responses. In the presence of lignocaine, the augmenting effects of veratridine and BDF 9148 on ventricular force were reduced. 6. In summary this study has shown that BDF 9148 prolongs the action potential and augments the contractile force responses of the rat right ventricle by a lignocaine-sensitive mechanism. BDF 9148 or similar drugs may have potential as positive inotropes in the treatment of heart failure.
Gen Pharmacol 1995 May
PMID:The effects of veratridine and BDF 9148 on the action potentials and contractility of the rat right ventricle. 778 34

The Epstein-Barr virus nuclear antigen-leader protein (EBNA-LP) is required for high efficiency B lymphocyte growth transformation by the virus. To test the potential contribution of EBNA-LP to tumorigenesis in vivo, we produced transgenic mice carrying an EBNA-LP cDNA construct, using the widely expressed metallothionein promoter. Expression of EBNA-LP was detected in liver, kidney, heart, lung and spleen. There were no apparent oncogenic consequences of EBNA-LP expression. Unexpectedly however, at ages ranging from about 4 months to over a year, transgenic mice developed symptoms of congestive heart failure, including left ventricular dilatation, right ventricular hypertrophy, left atrial thrombosis, pulmonary oedema and hydrothorax. Fibrillation was not apparent in the electrocardiograph; however a reduction in T-wave amplitude suggested that the development of an abnormality of ventricular repolarization may precede the manifestation of overt symptoms. The highly predictable development of dilated heart failure in these transgenic mice suggests they may be a useful model for the pathophysiological changes associated with human dilated cardiomyopathy.
J Gen Virol 1993 Jul
PMID:Dilated heart failure in transgenic mice expressing the Epstein-Barr virus nuclear antigen-leader protein. 839 79

1. The effects of several potassium channel blockers on the action potentials and contractile force of the electrically driven rat right ventricle have been determined. 2. Glibenclamide, which blocks the ATP-sensitive potassium channels, had no effect on the ventricular action potentials or contractile force responses. 3. 4-Aminopyridine, which blocks the Na(+)-activated potassium channels in ventricles, at 0.3-3 mM increased the amplitude and prolonged the action potentials, and also augmented the force responses to cardiac stimulation and to isoprenaline. 4. Clofilium, a selective blocker of the delayed outward rectifying potassium channel, at 0.1 and 0.3 microM prolonged the action potentials. At 0.1 microM, clofilium augmented the cardiac stimulation responses and, at 0.3 microM, clofilium augmented the maximal responses to isoprenaline. At 1 and 3 microM, clofilium had a lesser ability to prolong action potentials and did not alter force responses. 5. Procaine blocks the Na(+)-activated and the delayed outward rectifying potassium channels and, at higher concentrations, sodium channels. Procaine, at 30 microM, prolonged the action potentials and augmented the force responses to isoprenaline, presumably by blocking potassium channels. Procaine, at 1 mM, had no effect on action potentials but reduced the maximal force responses to isoprenaline, probably by blocking sodium channels. 6. Tetraethylammonium blocks the inward rectifying and delayed outward rectifying potassium channels. Tetraethylammonium, at 1 and 3 mM, prolonged the action potentials and augmented all of the force responses; these effects are likely to be predominantly due to blocking the outward rectifying potassium channel. Thus, in the presence of procaine, the effects of tetraethylammonium are predominantly due to the additional blockade of the inward rectifying potassium channel and there were no effects. 7. None of the potassium channel blockers at any of the concentrations tested had arrhythmogenic effects alone or in the presence of isoprenaline. 8. In summary, this study has shown that blockade of the Na(+)-activated and the delayed outward rectifying, but not the ATP-sensitive or inward rectifying, potassium channel is associated with prolongation of the action potentials, augments the contractile force responses, and is not arrhythmogenic on the rat right ventricle. New drugs that block the Na(+)-activated or delayed outward rectifying potassium channel may have potential as positive inotropes in the treatment of heart failure.
Gen Pharmacol 1996 Mar
PMID:Effects of potassium channel blockers on the action potentials and contractility of the rat right ventricle. 891 61

Left ventricular assist devices (LVADs) driven by external sources and capable of sustaining life over weeks to months as a bridge to heart transplantation have been implanted in over 300 patients in the United States. Because of the limited availability of organs for transplantation, the remarkable degree to which LVADs reverse end-organ dysfunction, and patient acceptance, proposals for home LVAD treatment and for use of the LVAD as a permanent treatment for heart failure are being considered. LVAD therapy is associated with characteristic psychiatric and psychosocial problems, however, which must be addressed to optimize results. Among the first 30 LVAD patients treated at our center, psychiatric interventions were frequently required for family stress, major depression, organic mental syndromes, and serious adjustment disorders. Psychiatric problems most often occurred in patients with ongoing medical complications following LVAD implantation, and often significantly impaired rehabilitation. Both depression and organic mental syndromes were frequently associated with preexisting cerebrovascular disease, which was sometimes occult, and with strokes complicating LVAD therapy. Aggressive treatment of depression played a major role in improving functional status. LVADs may decompress heart transplant waiting lists and make it possible to optimize patients' physiological and functional status before transplantation. With increased LVAD use, however, neuropsychiatric factors can be expected to play a large role in determining quality of life and outcome both before and after heart transplantation.
Gen Hosp Psychiatry 1996 Nov
PMID:Left ventricular assist devices. Psychosocial burden and implications for heart transplant programs. 893 21

Echocardiography is now considered to be the key investigation when heart failure is suspected, and should improve clinical management. An open-access echocardiography service was piloted to 24 general practitioners and the service was audited after 250 cases. The impact on clinical management was assessed by reviewing general practice notes 2 months after the echocardiogram. Significant impairment of left ventricular function was found in 49 patients (20%). Out of these subjects, 38 had been started on an ACE inhibitor. Twenty patients were considered to have a significant valve lesion by echocritiera, of whom 14 had been referred for a cardiological opinion. The provision of an open-access echocardiography service was popular with general practitioners and the information resulted in appropriate management decisions being made.
Br J Gen Pract 1996 Aug
PMID:Open-access echocardiography to general practitioners for suspected heart failure. 894 28

1. In this study, we investigated the influence of the inotropic agent and coronary vasodilator milrinone on platelet aggregation and intracellular levels of 3',5' cyclic adenosine monophosphate (cAMP) in human platelet-rich plasma (PRP) and whole blood (WB). Furthermore, we evaluated the influence of milrinone on the effects of adenosine, which reduces the platelet aggregation through an elevation of intraplatelet cAMP levels. 2. Milrinone decreased the platelet aggregation in response to agonists in both PRP and WB. A dose-dependent increase of intraplatelet cAMP levels was demonstrated: this result is in accordance with an effect on platelet phosphodiesterases. 3. Milrinone at low concentration and adenosine exerted additive effects on platelet aggregation and intraplatelet cAMP levels. 4. An interplay between milrinone and adenosine was shown in WB. Furthermore, dipyridamole, which prevents the uptake of endogenous adenosine, markedly enhanced the milrinone antiaggregating effect, whereas the adenosine receptor blocker, theophylline, decreased it. 5. The present data provide evidence that milrinone modulates the platelet function through an influence on intraplatelet levels of cAMP and it is able to interplay with substances stimulating adenylyl cyclase. 6. The interplay between milrinone and adenosine in the inhibition of the human platelet function could be effective during milrinone administration in the treatment of heart failure, when blood adenosine levels are significantly increased. These milrinone effects could be advantageous from a therapeutic point of view, since patients with heart failure are at risk of thrombosis and ischemic heart disease.
Gen Pharmacol 1996 Oct
PMID:Interplay between milrinone and adenosine in the inhibition of human platelet response. 898 Oct 60

To determine if physician specialty is associated with underutilization and underdosing of angiotensin-converting enzyme inhibitors among patients with heart failure, we reviewed the charts of 214 outpatients with decreased systolic function at an urban academic medical center. Regardless of whether patients were cared for by cardiologists, generalist physicians, or a combination of the two specialities, approximately 75% of the patients were taking an angiotensin-converting enzyme inhibitor. However, only approximately 60% of these patients were taking dosages proved to be efficacious in trials. Emphasis on adequate dosing is needed among all specialty groups.
J Gen Intern Med 1997 Sep
PMID:Utilization and dosing of angiotensin-converting enzyme inhibitors for heart failure. Effect of physician specialty and patient characteristics. 929 92

The objectives of this study were to examine the prevalence of depression in hospitalized, medically ill, older patients with and without congestive heart failure (CHF), and examine correlates, course, predictors of outcome, and treatment of depression in patients with CHF. A consecutive sample of 542 patients age 60 or over admitted to inpatient services of Duke University Medical Center were systematically screened by a psychiatrist for depression using the Diagnostic Interview Schedule; 342 depressed cases and nondepressed controls were identified. Of these, 107 had a primary or secondary diagnosis of CHF. Among patients with CHF, major depression was identified in 36.5%, a rate that was significantly higher than for patients without CHF (25.5%); the difference was largely explained by low rates of major depression in cardiac patients without CHF (17.0%) who had less severe physical illness. Minor depression was also present in 21.5% of CHF patients, but was not more prevalent than in patients without CHF (17.0%). Compared with nondepressed CHF patients, those with depression were more likely to have comorbid psychiatric disorder, severe medical illness, and severe functional impairment. Depressed patients used more outpatient and inpatients medical services, although this was largely due to the severity of their health problems. Patients often remained depressed for a prolonged period, and over 40% failed to remit during the year following discharge. Factors predicting slower remission included nonhealth-related, stressful life events and low social support; physical health factors at baseline had little effect. The majority of depressed CHF patients did not receive treatment for their depression with either antidepressants or psychotherapy, and did not see mental health specialists any more frequently than did the nondepressed. These findings are of concern and have important implications for the diagnosis and treatment of depression in older patients with heart failure.
Gen Hosp Psychiatry 1998 Jan
PMID:Depression in hospitalized older patients with congestive heart failure. 950 52

1. Taurine has recently been known to protect against ischemia and heart failure. Taurine possesses plenty of actions on the ion channels and transports, but is very non-specific. 2. Taurine may directly and indirectly help to regulate the [Ca]i level by modulating the activity of the voltage-dependent Ca2+ channels (also dependent on [Ca]i/[Ca]o), by regulation of Na+ channels, and secondly via Na-Ca exchange and Na(+)-taurine cotransport. 3. Taurine can prevent the Ca2+ ([Ca]o or [Ca]i)-induced cardiac functions. 4. Therefore, it seems possible that taurine could exert the potent cardioprotective actions even under the condition of low [Ca]i levels as well as under the Ca2+ overload condition. 5. The electrophysiological actions of taurine on cardiomyocytes, smooth muscle cells, and neurons from recent studies are summarized.
Gen Pharmacol 1998 Apr
PMID:Review of some actions of taurine on ion channels of cardiac muscle cells and others. 952 60


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