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)

Research findings to date indicate that there may not be a discrete change in contractile proteins in the common forms of heart failure. While the search for a defective myosin molecule in this context no longer seems promising, it remains plausible to propose "up-regulation" to a myosin variant with high ATPase activity as a means of increasing contractility in the failing heart.
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PMID:Contractile proteins of the heart. 622 89

Patients with acquired heart defects show oxidative phosphorylation disorders and reduced actomyosin ATPase activity. The markedness of changes is proportionate to the severity of valvular lesion as well as heart and myocardial failure. A relationship is demonstrated between disorders of energy generation and utilization, and contractility changes in the myocardium.
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PMID:[Interrelation of the processes of energy release and demand in the myocardium with its contractile function in acquired heart defects]. 623 92

The cardiovascular effects of 3,4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- qu inolinone ( OPC -8212) were investigated in isolated ventricular muscles of various mammalian species, anaesthetized dogs and conscious dogs. In the isolated ventricular muscles of the dog, cat, rabbit and guinea pig, OPC -8212 (3 X 10(-6)-3 X 10(-4) mol/l) increased the developed tension in a concentration-related manner and these positive inotropic effects of OPC -8212 were 1/140-1/120 those of dobutamine but 5-17 times and 8-25 times those of amrinone and theophylline, respectively. The positive inotropic effect of OPC -8212 was not modified by pindolol or phentolamine. In the isolated rat ventricular muscle, OPC -8212, amrinone and theophylline exerted no positive inotropic effect, although dobutamine did. In anaesthetized dogs, OPC -8212 (0.1-3 mg/kg i.v.) was nearly as active as amrinone in producing an increase in left ventricular contractile force. However, OPC -8212 was much less active than amrinone in increasing heart rate and decreasing blood pressure. In conscious dogs OPC -8212 at doses of 1 and 3 mg/kg i.v. increased peak LV dP/dt by 27% and 59%, respectively, without significant changes in heart rate and blood pressure. OPC -8212 did not affect the dog heart Na+,K+-ATPase activity. These results suggest the following: (1) OPC -8212 has a mechanism of action different from those of catecholamines and cardiac glycosides, (2) it has a useful profile in the treatment of heart failure because it caused a selective positive inotropic effect with no obvious positive chronotropic and vascular effects.
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PMID:In vitro and in vivo studies of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), a novel positive inotropic drug, in various animals. 633 64

In acutely uremic animals, the contractile force of the heart is consistently increased; such an increase can be dissociated from changes of afterload or catecholaminergic drive. It is associated with diminished sarcolemmal Na,K-ATPase activity in the heart which, in turn, may be related to increased levels of endogenous digitalis-like substances (endigens) that have been postulated to represent a natriuretic factor. In patients with chronic uremia, myocardial contractility is usually normal, but occasionally there may be heart failure unrelated to pre-existing hypertension, coronary heart disease, anemia, fluid overload, or other recognizable factors. So far, the experimental basis for this clinical observation is uncertain. Possible causes for the clinical syndrome include an excess of parathyroid hormone or cardiodepressor substances. There is experimental evidence of impaired cardiac response to beta adrenergic agonists, e.g., decreased isoproterenol-dependent calcium uptake, diminished inotropic and chronotropic responses. In acutely uremic rats, cardiac cyclic AMP levels are high but can be reversed by beta blockers. Heart calcium content is variable and heart weight is constantly increased in acutely uremic rats, despite decreased skeletal muscle mass. The change in heart weight is not related to anemia, to an excess of parathyroid hormone, or to sympathetic activity; its cause remains unknown. Experimental studies to date have shown a variety of abnormalities, but do not provide a uniform concept of the mechanisms or an explanation for the cardiac dysfunction so often observed in patients with uremia.
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PMID:Cardiac function in experimental uremia. 636 51

The loss of mechanical function in rat hearts subjected to either the calcium-paradox or global ischemia heart failure models was found to correlate with decreases in myocardial taurine levels. Therefore, the effect of taurine treatment was assessed in the two failure procedures. The presence of taurine protected against loss of mechanical function resulting from the calcium paradox and prevented both the large decline in sarcolemmal ATPase activities and the increase in sarcolemmal calcium binding normally associated with this model. Parallel studies on reperfused, taurine-untreated ischemic hearts showed only minor changes in these sarcolemmal functions. Taurine treatment normalized the slight increase in calcium binding associated with ischemia, but had no observable effect on recovery of mechanical function. Although taurine returns selected parameters of the sarcolemma toward normal in both models, it only improves mechanical function in the paradox model. This suggests that calcium paradox-induced heart failure is more closely associated with sarcolemmal dysfunction than ischemic heart failure.
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PMID:Effect of taurine on calcium paradox and ischemic heart failure. 645 Nov 84

In a naturally occurring model of congestive cardiomyopathy-round heart disease of turkeys, Ca2+ transport of isolated cardiac sarcoplasmic reticulum was evaluated at 1, 10, 28, and 56 days of age. Ca2+ binding in round heart disease birds was reduced to between 55% and 75% of values measured in age-matched commercial control turkeys (P less than 0.05 to less than 0.01). Similarly, Ca2+ uptake in round heart disease birds was reduced to between 52% and 87% of values measured in age-matched commercial control turkeys (P less than 0.05 and less than 0.01). Ca2+-stimulated ATPase values were similar in 1-, 10-, and 28-day-old round heart disease and commercial control turkeys. However at 56 days of age, when all round heart disease birds showed moderate to marked left ventricular dilatation. Ca2+-stimulated ATPase was reduced to 75% of control values (P less than 0.05). Depression of Ca2+ binding and Ca2+ uptake preceded the appearance of cardiac dilatation and may contribute to the pathogenesis of round heart disease. Depression of Ca2+-stimulated ATPase, present only after cardiac dilatation developed, appears to be secondary to cardiac failure. Sarcoplasmic reticulum function in round heart disease birds immunosuppressed by cyclophosphamide treatment (40 mg . kg-1 . d-1 for the first 4 days of age) was evaluated at 10 days of age. This treatment increased Ca2+ binding by 73% (P less than 0.05), and Ca2+-uptake by 58% (P less than 0.01) over values measured in untreated round heart disease birds. Reversal of the altered Ca2+ transport in sarcoplasmic reticulum by early immunosuppression supports the hypothesis that the immune system plays an integral part in the development of the congestive cardiomyopathy of round heart disease.
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PMID:Early alterations in the function of sarcoplasmic reticulum in a naturally occurring model of congestive cardiomyopathy. 645 87

Cardiogenic endotoxin shock (ES) refers to the intermediate and latter stages of ES characterized by a progressive myocardial dysfunction. This laboratory has been developing the hypothesis that a major etiology of this observed myocardial failure is a progressive state of global ischemia. In order to further test this hypothesis, ES (E coli, Difco Labs, 026:B6, 4 mg/kg) was induced in the canine model (n = 6) and coronary flow, myocardial contractility (dP/dtmax), and systemic hemodynamics were continuously monitored for five hours, following which the cardiac contractile proteins were isolated and characterized. In the ES group, control coronary flow (CF) = 90.5 +/- 3.6 ml/min/100 gm LV, coronary vascular resistance (CVR) = 61.82 X 10(3) +/- 2.28 X 10(3) dyne . sec. cm--5 and dP/dtmax 2,200 +/- 160 mm Hg/sec. Between four and five hours, CF decreased to 58.6 +/- 16 ml/min/100 gm LV, CVR increased to 128.6 X 10(3) +/- 18 X 10(3) dyne . sec. cm--5, and dP/dtmax decreased to 968 +/- 62 mm Hg/sec. Sham animals (n = 7) demonstrated no significant difference in CF, CVR, or dP/dtmax. Control myofibrillar ATPase activity demonstrated 50% activation (specific activity = 0.072 +/- 0.002 mumoles Pi/mg protein . min) at p Ca++ = 6.4, with no significant difference between endocardium and epicardium. ES myofibrils demonstrated 50% activation (specific activity = 0.060 +/- 0.002 mumoles Pi/mg protein . min endocardial, and 0.068 +/- 0.005 mumoles Pi/mg protein . min epicardial at pCa++ = 6.48 and 6.45, respectively, incriminating a change in affinity for Ca++ binding to the regulatory proteins. Thus, it would appear that the documented decrease in myocardial contractility is due in part to a depression of myofibrillar ATPase activity, which is related to a decrease in coronary flow, an increase in coronary vascular resistance, and a state of global myocardial ischemia.
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PMID:Cardiogenic endotoxin shock: coronary flow and contractile protein dysfunction as determinants of depressed cardiac contractility. 645

Abnormal responses are found in the early stages of heart failure with increased sympathetic and decreased parasympathetic activity, causing peripheral arteriolar vasconstriction and tachycardia respectively. The cardiopulmonary baroreflex may be studied by decreasing venous return ("low body negative pressure") and by measuring vascular resistance forearm. The arterial baroreflex may be studied by changing aortic pressures (by intravenous phenylephrine or nitroglycerin). Orthostatism and the tilt test deactivate the cardiopulmonary and arterial baroreflexes simultaneously. These baroreflexes are impaired in patients with heart failure. Their activation does not cause the usual sympatho-inhibition so contributing to increased sympathetic tone. This dysfunction may result from a change at any point on the reflex pathway: the baroreceptors themselves, the afferent, central and efferent pathways. It is selective as during the cold pressor test, the vasoconstrictor response remains intact. One of the possible mechanisms of baroreflex dysfunction in heart failure is loss of sensitivities of the baroreceptors. This may be multifactorial: structural abnormalities, changes in compliance or functional abnormality. Even if the loss of sensitivity is partially related to a change in compliance, other factors play a role. It is more functional than structural abnormalities because, after cardiac transplantation, the baroreceptors regain their sensitivity within 2 to 3 weeks. Excessive Na-K dependent ATPase activation of the smooth muscle cells of the carotid sinus could lead to hyperpolarization of the cell membrane, so reducing the excitability of the receptor. Aldosterone is one of the factors which could activate the Na-K ATPase, as this hormone directly increases pump activity and favorizes the synthesis of new pumps in the vascular smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Baroreflexes and congestive heart failure]. 748 98

The aims of treatment of chronic heart failure are to improve the symptoms and the quality of life, reduce mortality and prevent left ventricular dysfunction. Before the first symptom occurs, neurohormonal activation takes place (increased catecholamines and atrial natriuretic peptide levels). Diuretics improve symptoms and are irreplaceable for the elimination of salt and water overload. Loop diuretics are used more often than the thiazides. Their deleterious effects on electrolyte balance are well known. The fact that they activate the renin angiotensin system is a more recent acquisition; the increase in plasma renin activity is a poor prognostic factor. Diuretics potentialize the vasodilator effect of angiotensin converting enzyme inhibitors which inhibit the neurohumoral activation induced by the diuretics. This therapeutic association is very logical, effective and allows reduction in the dosage of the diuretic. To date, there are no large scale controlled studies of the effects of diuretics on mortality. Spironolactone corrects hypokalaemia and hypomagnesaemia induced by loop diuretics. Moreover, it has been shown experimentally in renovascular hypertension and in hyperaldosteronism, that this molecule can prevent myocardial fibrosis, a factor which leads to ventricular dysfunction. The RALES study will analyse the effect of associating spironolactone to diuretic and ACE inhibitor therapy on the mortality of patients in NYHA classes III-IV. The value of digitalis in heart failure patients with sinus rhythm is a classical controversy. Digitalis has a positive inotropic effect (inhibition of NaK-dependent ATPase). More recently, a favourable neurohormonal effect has been reported; digitalis decreases the activation of the sympathetic and renin-angiotensin systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Classic treatment of chronic heart insufficiency. What if new?]. 748 8

Na,K-ATPase receptor density has been shown to be down-regulated with decreasing ejection fraction in patients with chronic heart failure. It was the aim of the present study to determine whether down-regulation is detected also at the mRNA level. Six donor hearts and six explanted hearts due to dilated cardiomyopathy (ejection fraction 23 +/- 5%) were analyzed. RNA was extracted. Quantitative Na,K-ATPase receptor catalytic subunit alpha 1, alpha 2 and alpha 3 mRNA expression was determined by solution hybridization. No cross-reactivity occurred between the three probes. alpha 1 mRNA was expressed at about 5 and 10 times higher (p < 0.001) concentrations than alpha 2 and alpha 3 mRNA, respectively, and alpha 2 mRNA higher (p < 0.001) than alpha 3. There were no differences between right and left ventricles and between donor hearts and patients with dilated cardiomyopathy. In conclusion, Na,K-ATPase alpha 1 mRNA is the predominant subunit expressed in human myocardium. Depressed ejection fraction in dilated cardiomyopathy is not associated with changed mRNA subunit expression. Documented downregulation of Na,K-ATPase activity, therefore, may be associated with the structural and membrane-related beta subunit or posttranscriptional modification of the catalytic subunits.
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PMID:Na,K-ATPase receptor subunits alpha 1, alpha 2 and alpha 3 mRNA in dilated cardiomyopathy. 755 Jan 31


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