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)

Most pharmacokinetic and biologic attributes of digitalis are age dependent. They are determined in great measure by the chemical structure of the specific cardiac glycoside being used. These effects differ in the intact normal circulation and in heart failure because of the altered autonomic nervous system and hormonal control that exist in the latter. Digitalis is effective only in the presence of myocardial dysfunction, but in a clinical setting, cardiac performance may be difficult to gauge; improved tools are needed for this purpose. The dosages of digoxin recommended for infants and children have been steadily reduced in the past decade, and there is no good evidence that more favorable risk-to-benefit ratios are achieved when higher doses are used or when higher plasma concentrations are sought. Massive digitalis toxicity is a serious, often fatal, complication in young infants, especially when the drug is given parenterally; it may be difficult to diagnose early. The only reliable deterrent for this complication is the adoption of careful safety standards whenever the drug is employed. Experience with digoxin antibodies is still scarce in children, especially in infancy, but their use generally has been associated with a favorable outcome. Endogenous substances that interfere with the digoxin radioimmunoassay (DLIS) occasionally yield clinically relevant, erroneously high, plasma digoxin concentration readings in neonates. An interesting hypothesis currently being investigated is the physiologic and pathologic role of these compounds in sodium hemostasis; they may be part of a putative endogenous NaK-ATP-ase inhibitor involved in the pathogenesis of hypertension and renal diseases.
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PMID:Digitalis, digitalis antibodies, digitalis-like immunoreactive substances, and sodium homeostasis: a review. 306 50

Rats were fed a diet containing beta-guanidinopropionic acid (GP), an inhibitor of creatine transport. After 6 to 8 weeks of feeding the myocardial creatine (Cr) and phosphocreatine (PCr) stores were severely depleted while ATP content was normal. Hearts of GP-treated rats perfused according to Neely's working heart model revealed clear cardiac contractile failure: the maximal work capacity at a stepwise increase in resistance as well as the maximal oxygen consumption were 32 to 40% less in the GP group. The cardiac failure in GP-treated working hearts was associated with a rise in the left ventricular diastolic pressure, which could cause a diminished cardiac output probably due to impaired LV filling. The extent of the contractile failure was found to depend on functional load and on the degree of Cr (PCr) substitution. The energy fluxes through creatine kinase measured by the 31P-NMR saturation transfer technique were diminished by a factor of two after substitution of 90% of creatine, but still exceeded the rate of ATP turnover. The results are compatible with the concept of phosphocreatine pathway for intracellular energy transport and show that PCr is an important high energy phosphate compound for cardiac contractile function.
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PMID:The cardiac contractile failure induced by chronic creatine and phosphocreatine deficiency. 321 3

The effects of graded hypoxia, graded reoxygenation after anoxic perfusion and of different extracellular K+-concentrations on cardiac energy metabolism and performance were studied in isolated, perfused, electrically paced rat hearts. Graded hypoxia was induced by different oxygen partial pressure (PO2: 736 to 43 mmHg, nine intermediate steps; O2 supply: (AVD*CF): 300 to 21 microliters/g*min) in perfusate for 3 min, thus leading to different levels of relative mechanical steady state. Evaluated free energy change of ATP-hydrolysis (dG/d zeta) decreased largely in parallel with peak systolic pressure (Psyst) and systolic dP/dtmax, whereas diastolic dP/dtmin declined already to lowest values with moderate hypoxia. For regular beats and beats potentiated by paired stimulation the same relationships were found. Complete reoxygenation of hearts perfused anoxically beforehand (10 or 30 min, PO2 less than 6 mmHg), restored Psyst and dG/d zeta completely. Graded reoxygenation from different levels of hypoxia resulted in restitution of dG/d zeta and Psyst to the same levels as in graded hypoxia. The inotropic effect of paired stimulation was moderately reduced. Cytosolic Pi-levels remained increased during partial reoxygenation and exhibited no distinct relationship with mechanical performance. High extracellular K+ (13.5 mM) resulted in increased Psyst and elevated dG/d zeta-levels. Cardiac failure during graded hypoxia and high K+ occurred at comparatively high dG/d zeta levels. Reoxygenation with high K+, led to recovery of dG/d zeta levels but not of Psyst values. According to the results obtained in early hypoxic failure free energy dependence of Na+/K+-ATPase is of minor relevance whereas free energy dependence of sarcoplasmic Ca2+ regulating processes appears to be important.
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PMID:Myocardial performance and free energy of ATP-hydrolysis in isolated rat hearts during graded hypoxia, reoxygenation and high Ke+-perfusion. 324 7

Myosin form birefringence has been studied in cryostat sections of left ventricular myocardium from the dog and human. The muscle in such sections has been shown to demonstrate the sliding filament phenomenon. The sarcomere length of canine myocardium agreed with that found in comparable electron micrographs. Unexpectedly, it was found that glycerol, normally used as an inert and optically ideal mountant, caused profound change in myosin birefringence. This apparently invalidates results obtained with this mountant. The absolute birefringence found in these sections, whether mounted in glycerol or in an ATP-calcium buffer, corresponded to values found by other workers with skeletal muscle and isolated myosin. However, the birefringent properties (optical path difference: o.p.d.) of well functioning muscle was found to be low, the o.p.d. increasing when exposed to ATP and calcium. Poorly functioning muscle could be distinguished from well functioning muscle on the basis of its higher 'in air' o.p.d. This difference correlated well with physiological assessments of myocardial function or with clinical assessments of cardiac failure. Evidence is presented indicating that changes in apparent birefringence, caused by ATP-calcium or by anoxia, are due to altered orientation of the myosin micelles and can be inhibited by agents that inhibit myosin ATPase activity.
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PMID:Increased myosin orientation during muscle contraction: a measure of cardiac contractility. 383 15

There is a decrease in total adenine nucleotides, cyclic AMP (cAMP), ATP/total ADP, and phosphocreatine (PCr)/creatine (Cr) both in situ and in the perfused heart in the heart failure stage of the cardiomyopathic Syrian hamster. There were decreases in developed pressure, dP/dt, and O2 consumption associated with the decrease in total adenine nucleotides and cAMP. Cardiomyopathic Syrian hamsters (180-240 days old) with congestive heart failure were given water with the calcium entry blocker, verapamil, as an additive 2 mo before death. In the cardiomyopathic group given verapamil the adenine nucleotides, cAMP, and high-energy phosphates were preserved and cardiac performance was not significantly different from that of the verapamil-treated healthy hamsters at the time of death. Pretreatment of cardiomyopathic animals with verapamil (6.6 mg verapamil/ml water consumed by drinking) resulted in significantly higher ATP/total ADP and PCr/Cr compared with nontreated cardiomyopathic hamsters. This is the first report demonstrating that a calcium entry blocker may improve cardiac performance and preserve total adenine nucleotides during the heart failure stage of the cardiomyopathic hamster.
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PMID:Verapamil preserves adenine nucleotide pool in cardiomyopathic Syrian hamster. 394 35

Trabecular preparations from the hog heart right ventricle were "skinned" by treatment with Lubrol WX and glycerol. Ca++ activated isometric contractions were gradedly relaxed by inorganic phosphate (Pi) in the millimolar range or vanadate (Vi) in the micromolar range while tension cost (ATP split/force generated) was increased by a factor of 1.75. From measurements of force, ATPase activity, immediate stiffness and stretch activation, evidence is provided that the mechanical deactivation and the increase in tension cost may result from an acceleration of the myosin cross-bridge cycle, due to a direct interference of Pi and Vi with the chemomechanical energy transformation at the contractile proteins. The possible significance of such a mechanism in cardiac failure or muscle fatigue is discussed.
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PMID:Phosphate and vanadate reduce the efficiency of the chemo-mechanical energy transformation in cardiac muscle. 621 26

The present study concerns the morphological and biochemical lesional picture of the myocardium in cases of acute heart failure induced by various experimental models: ligature of the coronary artery, direct electric stimulation of the heart by catheterism, lethal hemorrhage, pneumothorax, beta-adrenergic shock. Worthy of note was the similitude of the lesional myocardium pictures characterized electron microscopically by a wide range of lesions, from reversible to focal cytolysis, and biochemically by decrease of mitochondrial enzymes, ATP, Mg2-1 X K+ and increase of Na+ X H2O, Ca2+. Problems linked to the pathogenesis, reversibility of the lesions and efficiency of certain therapeutical means are discussed.
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PMID:Myocardial lesions in experimental acute heart failure. 623

The development of myocardial infarction was shown to be accompanied by a rise in blood cAMP, cGMP and AMP levels, cyclic nucleotides peaking within the first hours of the disease. The increase in plasma cAMP, associated with developing heart failure, was more persistent. The administration of GIP mixture during the acute phase of myocardial infarction was conducive to lowering the levels of cyclic nucleotides and AMP, and raising blood ATP and ADP values. Clinically, the effect of GIP was manifested in reduced ventricular arrhythmias and diminished signs of heart failure.
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PMID:[Effect of a glucose-insulin-potassium mixture on the cyclic and adenine nucleotide levels in the acute period of myocardial infarct]. 633 82

A high proportion of the "intermediate" muscle fibres, which are semi-dark after both acidic and alkaline preincubation in ATP-ase staining, was found in the thigh with heart failure. Characteristic patterns of fibre splitting were found mostly in jumpers' muscles. Possibilities of fibre subgroup transformation and fibre hyperplasia due to training are discussed.
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PMID:Data on muscle fibre conversion and fibre splitting in man. 645 93

Maitotoxin is a substance extracted from a dinoflagellate and certain tropical poisonous fish. It is considered as the most potent marine toxin (50 times more potent than tetrodotoxin). In isolated mammalian atria, maitotoxin produces at low doses a positive inotropic effect not modified by reserpine pretreatment and suppressed by Mn2+ ions. In the anaesthetized cat, it induces cardiac arrhythmias and tachycardia leading to cardiac failure. On the other hand, maitotoxin strongly inhibits Na+-K+ ATP-ase from microsomes of cat and human kidneys. In a rat pheochromocytoma cell line, it has been shown to promote a norepinephrine release and an increase in Ca2+ influx. The purpose of this work is to study the effect of maitotoxin on action potential of isolated perfused rat heart to check the existence of a direct effect on the myocardium.
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PMID:Effects of highly purified maitotoxin extracted from dinoflagellate Gambierdiscus toxicus on action potential of isolated rat heart. 654 Aug 11


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