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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Force development and shortening by cardiac muscle occur as a result of the interaction between actin and myosin within the myofibrillar lattice. This interaction is dependent upon intracellular ionized calcium and is controlled by the troponin-tropomyosin regulatory proteins situated along the actin filament. In this study, we compared the myofibrillar content and myofibrillar Mg-ATPase activity of normal human ventricular muscle with that of ventricular muscle from patients in end-stage failure caused by coronary artery disease or cardiomyopathy and ventricular muscle from patients with heart failure due to mitral valve insufficiency. The results show that the amount of myofibrillar protein (mg/g wet wt ventricle) in hearts in end-stage failure (coronary artery disease and cardiomyopathy) is significantly lower compared with normal hearts and hearts in failure due to mitral valve insufficiency. However, the Mg-ATPase activity of myofibrils from hearts in both end-stage failure and failure due to mitral valve insufficiency is significantly lower compared with myofibrils from normal hearts. The data suggest that the reduction in the amount of myofibrillar protein in ventricular tissue is a pivotal event that may be responsible for the progression of heart disease to the point of end-stage failure.
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PMID:Changes in myofibrillar content and Mg-ATPase activity in ventricular tissues from patients with heart failure caused by coronary artery disease, cardiomyopathy, or mitral valve insufficiency. 296 7

In most animal species, left ventricular hypertrophy due to pressure overload is associated with an advantageous increase of the "slow" V3 isomyosin. In contrast, in spontaneously hypertensive turkeys, the development of left ventricular hypertrophy is associated with the synthesis of a "fast" V1-like isomyosin, with high incidence of cardiac failure. This could be related to the high catecholamine levels found in these animals. This is why we studied the ventricular myosin pattern after lowering of blood pressure and regression of cardiac hypertrophy obtained by means of labetalol, and alpha- and beta-blocking drug which inhibits the effects of catecholamines. From the 2nd to the 32nd week of age, 22 turkeys were treated with increasing doses of p.o. labetalol (from 20 to 35 mg/kg body weight daily) and 16 other turkeys were given daily p.o. placebo. Blood pressure and heart rate were periodically measured by an indirect method. After sacrifice, the degree of cardiac hypertrophy was evaluated by the biventricular weight to body weight ratio, ventricular myosin was purified, Ca++-activated ATPase activity assessed, and ventricular myosin pattern was determined by two-dimensional gel electrophoresis of myosin heavy chains. Plasma and cardiac catecholamines were measured by high performance liquid chromatography. Throughout the study period, blood pressure and heart rate were significantly reduced in the labetalol-treated animals as compared to the untreated ones. At the end of the study period, the ventricular mass was significantly lower in the labetalol group. Nevertheless, no differences were observed in ventricular myosin pattern and Ca++-activated ATPase activity levels between the two groups. In the labetalol group, an increase in plasma catecholamines and only a slight, but not significant, increase in cardiac catecholamines was found. These data indicate that in spontaneously hypertensive turkeys, the synthesis of the "fast" V1-like isomyosin is not influenced by known pathophysiological stimuli like blood pressure, cardiac hypertrophy and catecholamines.
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PMID:Ventricular myosin pattern of spontaneously hypertensive turkeys is unaffected by labetalol treatment. 297 Aug 41

The present study has examined early cellular effects of chronic adriamycin administration to dogs using a protocol (1 mg/kg/week to a total cumulative dose of 240 mg/m2) producing significant but small reductions in ejection fraction and stroke volume as determined echocardiographically prior to the development of clinical or radiological manifestations of heart failure. At this early phase of cardiomyopathy, significant reduction (P less than 0.05) in sarcoplasmic reticulum Ca2+, K+-ATPase was observed without any change in mitochondrial, lysosomal or sarcolemmal marker enzymes. Myocardial calcium (P less than 0.01) and glutathione (P less than 0.001) levels were increased significantly. Detailed analysis of myocardial phospholipid profiles failed to show any significant differences between control and treated dogs. In contrast, red cell membranes showed increased phosphatidylcholine (PC) and decreased phosphatidylserine (PS) contents, resulting in a significant increase in PC/PS ratio (P less than 0.05). No significant changes were detected in activities of catalase, superoxide dismutase or glutathione peroxidase in erythrocytes or myocardial tissue from control and adriamycin-treated animals. A significant (P less than 0.05) elevation in plasma sialic acid was observed following adriamycin treatment. Our results suggest that early adriamycin-induced damage is unlikely to result from alterations in cellular processes protecting tissues against oxidant injury. Regression analysis indicated that, of the various abnormalities observed, only the elevated myocardial calcium levels and the increases in plasma sialic acid correlated with the degree of myocardial functional impairment. Our findings suggest the presence of sarcolemmal alterations in Ca2+ handling in early adriamycin-induced myocardial injury and indicate that measurement of plasma sialic acid should be further investigated as a possible noninvasive indicator of impending adriamycin cardiotoxicity.
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PMID:Adriamycin cardiomyopathy: implications of cellular changes in a canine model with mild impairment of left ventricular function. 299 97

Digitalis glycosides inhibit Na+K+-ATPase in the cells and have been used for scientific studies of cation transport over cell membranes. Furthermore, digitalis has a positive inotropic and antiarrhythmogenic effect. Specific binding sites for digitalis glycosides have been observed in erythrocytes, the myocardium and the central nervous system. Transcellular transport of digoxin has been found in the kidney, since digoxin is excreted by tubular secretion. Recent studies have discovered an endogenous digitalis-like substance both inhibiting Na-K-ATPase and displacing digoxin from specific binding sites at the erythrocytes. The concentration of this component in plasma seems to be higher in hypertension than in normotension. Future studies will have to disclose other effects of this substance in order to evaluate whether it can be used as a drug in heart failure.
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PMID:Positive inotropic drugs--digitalis. 301 57

Doxorubicin (Adriamycin), a potent antineoplastic drug, produces progressive cardiotoxicity which may lead to ultimate cardiac failure. The effects of chronic doxorubicin treatment on cardiac actomyosin ATPase were the principal focus of the present studies. This approach was based on the established correlation between cardiac contractility and contractile protein ATPase activity. Rabbits were injected intravenously with doxorubicin (4 mg/kg) at weekly intervals for 1-7 weeks. Body weight increase was attenuated in the treated animals; heart weight/body weight ratio was unchanged. Actomyosin and water contents of ventricular muscle were not different in doxorubicin-treated as compared with vehicle control animals. Cellular damage was detected histologically after one dose of doxorubicin (equivalent to a single clinical dose), and was extensive after 4-5 weeks of treatment. Animals which received 1-2 injections of doxorubicin demonstrated a 29% average increase in actomyosin ATPase activity as compared to vehicle controls; this difference was highly significant (p less than 0.001). Further treatment with doxorubicin tended to progressively decrease ATPase activity. It is suggested that the increased actomyosin ATPase activity seen with low total doses of doxorubicin may represent a compensatory mechanism for maintenance of contractility; this interpretation is supported by the clinical observation that the morphologic evidence of progressive doxorubicin toxicity is not associated with a parallel decrease in contractility, until severe cumulative toxicity has been induced.
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PMID:Cardiac actomyosin ATPase activity after chronic doxorubicin treatment. 315 43

Experimental hyperthyroidism induced in rats by daily injections of 3,3',5,5'-tetraiode-L-thyroxine (0.5 mg/kg i.p.) for 14 days resulted in a significant increase in heart weight and heart weight/body weight ratio. Hemodynamic and morphological studies were performed in one group. Thyroxine-treated rats showed a characteristic cardiovascular hyperdynamic state, such as tachycardia and augmented rate of contraction, but no evidence of heart failure such as elevated end-diastolic pressures. The cardiac cells in hyperthyroid rats had a significantly larger diameter and more mitochondria than did those of the control rats. In another group the activities of cardiac enzymes involved in energy utilization and liberation were measured biochemically and compared with those of normal controls. Hyperthyroidism resulted in increased specific activity of cytochrome C oxidase and actomyosin ATPase in the myocardium. The specific activity of long-chain acyl-CoA synthetase, carnitine palmityl-transferase, carnitine acetyltransferase, malate dehydrogenase and citrate synthase showed a moderate to marked increment, whereas the specific activity of lactate dehydrogenase and pyruvate kinase remained at the control values. These results suggest that in hyperthyroid rat hearts the functions of both energy liberation and utilization systems are enhanced to meet the added workload. Moreover, the increased activity of the enzymes participating in fatty acid metabolism suggest that in thyroxine-induced hypertrophic and hyperdynamic rat hearts, fatty acids contribute more to the energy supply than do carbohydrates.
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PMID:Biochemical and morphological study of cardiac hypertrophy. Effects of thyroxine on enzyme activities in the rat myocardium. 315 81

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

After prolonged ischemia followed by reperfusion of the isolated rat heart, irreversible heart failure is associated with creatine kinase leakage from the cells. The possible implications of MM creatine kinase leakage from myofibrillar compartments on the contractile properties of ventricular muscle have been studied in control versus ischemic hearts. Total creatine kinase activity decreased in ischemic cells while creatine kinase and ATPase activities were not modified in isolated myofibrils. The efficiency of creatine kinase and phosphocreatine in the relaxation of rigor tension in skinned ventricular preparations was not changed after ischemia. Furthermore, neither the pCa/tension relationship nor the rate of tension development following length changes were modified by ischemia. These results show that the contractile properties of myofilaments as well as the functional coupling between myosin ATPase and creatine kinase are preserved in ischemic hearts suffering irreversible contractile failure.
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PMID:Contractile properties and creatine kinase activity of myofilaments following ischemia and reperfusion of the rat heart. 343 83

A decrease in cardiac function and intracellular calcium, and an increase in cardiac sarcolemmal ATPase have been reported in experimentally induced aortic stenosis of 6 to 9 months duration. Prazosin has been used in the treatment of heart failure due to mechanical ventricular overload. It is, however, not known whether prazosin treatment gives only hemodynamic benefit with accompanying subjective improvement or if it also improves the condition of the myocardium in terms of contractility and biochemical changes. The present investigation deals with the effects of 3 months of prazosin treatment on cardiac function, electrolytes, and ATPase in dogs with aortic stenosis of 3 months duration. Although there were no significant changes in most of the left and right ventricular hemodynamic parameters, the left ventricular end-diastolic pressure increased significantly after 3 months of aortic stenosis. Prazosin prevented further deterioration of cardiac function. All the dogs developed left ventricular hypertrophy and all chest X-rays showed cardiomegaly. Concomitant with these changes, there was a tendency towards a decrease in total tissue Ca++ and intracellular Ca++ and K+ and a tendency towards an increase in sarcolemmal Na+-K+-ATPase. Prazosin treatment, although it markedly reduced left ventricular end-diastolic pressure, did not reduce the cardiomegaly. There were no significant changes in any of the other hemodynamic parameters. Prazosin treatment decreased sarcolemmal ATPase and tended to increase intracellular Ca++. It appears therefore that prazosin not only tends to bring the cardiac function towards control values but also tends to correct the ATPase and intracellular Ca++ levels of the failing heart.
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PMID:Effect of prolonged prazosin treatment on hemodynamic and biochemical changes in the dog heart due to chronic pressure overload. 608 30

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


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