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)

Chronic, rapid ventricular pacing produces congestive heart failure in dogs. The objectives of this study were to determine whether or not (i) in vitro myocardial biochemical alterations reported for heart failure by volume or pressure overload also occurred with heart failure due to rate overload, and (ii) these biochemical alterations were related to relevant in vivo cardiac physiologic alterations. We compared 27 dogs that were paced to advanced heart failure with 21 sham-operated dogs. Dogs with heart failure had 55% lower left ventricular ejection fraction (22.5 +/- 7.6 vs. 50.5 +/- 5.1%) and cardiac index (81 +/- 22 vs. 178 +/- 48 mL.min-1.kg-1), 287% higher pulmonary capillary wedge pressure (27.5 +/- 6.8 vs. 7.1 +/- 3.4 mmHg; 1 mmHg = 133.3 Pa), and 64% greater left ventricular diastolic area (18.4 +/- 3.7 vs. 11.2 +/- 1.3 cm2) (all p less than 0.05). Dogs with heart failure also had (i) 69% lower norepinephrine (232 +/- 139 vs. 747 +/- 220 ng/g protein), (ii) 25-50% lower activities of myofibrillar Ca ATPase (0.188 +/- 0.026 vs. 0.253 +/- 0.051 U/mg myofibrils), sarcoplasmic reticulum Ca-transport ATPase (0.155 +/- 0.074 vs. 0.288 +/- 0.043 U/mg membrane), and the glycolytic enzyme phosphofructokinase (33.4 +/- 10.0 and 47.7 +/- 15.8 U/g), (iii) 32% higher activity of the beta-oxidation enzyme hydroxyacyl-CoA dehydrogenase (11.43 +/- 1.48 vs. 8.67 +/- 1.70 U/g), and (iv) 60% higher activity of Krebs cycle oxoglutarate dehydrogenase (2.89 +/- 0.77 vs. 1.81 +/- 0.95 U/g) (all p less than 0.05). No differences between groups were observed for isozyme patterns and ATPase activity of myosin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies. 232 42

Circular dichroism (CD) spectra of myocardial G-actin significantly differ from those of F-actin, and the spectra of G- and F-actins differ from those of myocardial tropomyosin, native tropomyosin and alpha-actinin. In heart failure in man and experimental animals, characterized by a significantly decreased ability of the contractile protein system to generate force, considerable changes in the tertiary structure of Straub G-actin are observed. During polymerization a monomer of this actin is included in F-actin as a promoter without corresponding conformational changes of a part of G-actin globule; G-actin from the failing myocardium loses its conformational mobility. According to CD data the secondary protein structure is not altered. CD spectra analysis with regard to the regions of aromatic amino acid residue localization in active sites of actin suggests that the sites of actin-myosin and actin-actin interactions do not assume the conformation necessary for normal functioning of thin filaments.
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PMID:Conformational state of thin myofilament proteins in normal and chronically failing heart. 235 86

The hemodynamic response to maximal exercise was determined in sedentary and trained rats with a chronic myocardial infarction (MI) produced by coronary artery ligation and in rats that underwent sham operations (SHAM). Infarct size in the MI groups of rats comprised 28-29% of the total left ventricle and resulted in both metabolic and hemodynamic changes that suggested that these animals had moderate compensated heart failure. The training regimen used in the present study produced significant increases in maximal O2 uptake (VO2max) when expressed in absolute terms (ml/min) or when normalized for body weight (ml.min-1.kg-1) and consisted of treadmill running at work loads that were equivalent to 70-80% of the animal's VO2max for a period of 60 min/day, 5 days/wk over an 8- to 10-wk interval. This training paradigm produced two major cardiocirculatory adaptations in the MI rat that had not been elicited previously when using a training paradigm of a lower intensity. First, the decrement in the maximal heart rate response to exercise (known as "chronotropic incompetence") found in the sedentary MI rat was completely reversed by endurance training. Second, the downregulation of cardiac myosin isozyme composition from the fast ATPase V1 isoform toward the slower ATPase (V2 and V3) isoforms in the MI rat was partially reversed by endurance training. These cardiac adaptations occurred without a significant increase in left ventricular pump function as an increase in maximal cardiac output (Qmax) and maximal stroke volume (SVmax) did not occur in the trained MI rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac adaptations to endurance training in rats with a chronic myocardial infarction. 252 73

Rats treated with the alkaloid monocrotaline developed right ventricular hypertrophy with a left:right ventricle weight ratio of 1.35 +/- 0.10 (mean +/- s.e.m., n = 25) compared with 3.83 +/- 0.40 (n = 14) in diet-matched controls (P less than 0.001). Urine volume and sodium content were reduced and body water increased consistent with heart failure. In 10 out of 26 treated rats pleural, pericardial or peritoneal effusions were present. Urine norepinephrine content was significantly raised (P less than 0.02) but epinephrine was unchanged. Plasma norepinephrine levels were raised though not significantly. Myocytes isolated from the right ventricle had a reduced myosin Ca2+-activated ATPase (P less than 0.05) activity and a shift towards slower V2 and V3 myosin isoforms. There was no decrease in maximum contraction amplitude with calcium or isoproterenol in either left or right ventricular cells of treated rats. Right ventricular cells from treated rats showed a reduced rate of contraction in maximum isoproterenol (P less than 0.05) and a significant rightward shift in PD2 (P less than 0.05) representing a two-fold increase in EC50 for isoproterenol compared with right ventricular cells from control animals. There was no shift in EC50 for isoproterenol in left ventricle cells. In parallel experiments, myocytes isolated from both ventricles of rats treated with isoproterenol for one week showed a rightward shift of more than 50-fold in the isoproterenol concentration-response curve and a depressed response to maximum isoproterenol. In the rat monocrotaline model of right-sided cardiac hypertrophy and failure, changes in sensitivity to beta-adrenoceptor agonists are slight, and present only in the right ventricle. The lack of change in the left ventricle seems to suggest that this functional desensitisation is not a consequence of raised circulating catecholamines.
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PMID:Isoproterenol sensitivity of isolated cardiac myocytes from rats with monocrotaline-induced right-sided hypertrophy and heart failure. 255 26

Congestive heart failure was induced in rabbits by a chronic treatment with a low dose of adriamycin (0.75 mg/kg intravenously 3 times per week for 11 weeks). Twenty-four to 48 h after the last injection, adriamycin-treated rabbits had a three-fold increase in plasma norepinephrine, a seven-fold increase in plasma epinephrine, a 19 +/- 8% increase in heart rate, and a 54 +/- 10% decrease in the total tension generated by their isolated papillary muscles, when compared with normal age-matched controls. This demonstrated the occurrence of the cardiomyopathy and heart failure. The effect of adriamycin on myocardial and diaphragmatic protein synthesis was examined in vivo after a 1-h infusion with [3H]leucine and in vitro after a 2-h incubation of right ventricular papillary muscle with [3H]leucine. The rate of in vivo [3H]leucine incorporation into total protein was increased in the heart of the adriamycin-treated rabbits. The increases were 60 +/- 16% in the left ventricle, 49 +/- 18% in the septum, 32 +/- 18% in the right ventricle, and 66 +/- 16% in the atria. A similar increase was observed when measuring the rate of [3H]leucine incorporation into myosin, a myofibrillar protein, and when the rate of [3H]leucine incorporation into total protein was measured in vitro in papillary muscle. In contrast, the rate of [3H]leucine incorporation into total protein of the diaphragm was not significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein synthesis is increased in heart failure induced by low dose adriamycin in rabbits. 274 6

The epidemiology and etiology, pathophysiology, diagnosis, and treatment of congestive heart failure (CHF) are reviewed. CHF affects as many as 4 million Americans and is one of the most prevalent causes of death in hospitalized patients. Major risk factors for developing CHF include advanced age, male sex, hypertension, coronary artery disease, smoking, hypercholesterolemia, diabetes mellitus, and rheumatic heart disease. Heart failure results from decreased intrinsic myocardial contractility caused by one or more of three changes: (1) altered adrenergic nervous system function, (2) impaired delivery of calcium to contractile elements in the heart, and (3) reduced myosin-ATPase activity in the myocardium. The disease is progressive, and no intervention has yet been found to stop it effectively. CHF is diagnosed based on subjective signs and symptoms and objective assessment using auscultation, ECG, chest roentgenogram, laboratory tests, and noninvasive and invasive tests. Treatment of CHF begins with restriction of physical activity and sodium intake. Pharmacologic interventions start with either digitalis glycosides or thiazide diuretics; both may be used concomitantly as the disease progresses. Current studies are focusing on the use of angiotensin-converting enzyme inhibitors as first-line agents for CHF. When CHF worsens, loop diuretics are substituted for or added to the thiazide diuretics, and vasodilators are added to reduce the workload on the heart. Other inotropic agents, including the new bipyridine derivatives, may also be used. In patients not responding to these and other aggressive therapeutic interventions, cardiac transplantation is the only option. Despite advances in management of CHF, little improvement in overall survival has been demonstrated, and no intervention has stopped or reversed the progression of CHF.
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PMID:Current concepts in clinical therapeutics: congestive heart failure. 287 92

The increase of the muscular mass of the left ventricle represents, for the ventricular pump, a mechanism of adaptation to a normal process (growth, sport, etc.) or a pathological process (mechanical overload or cardiomyopathy). The geometrical variations which are associated, tend to normalize the performances and/or the systolic constraints, determining elements of the metabolic needs of the myocardium. If left ventricular hypertrophy is not quantitatively, geometrically and functionally adequate and if the contractility and precharge reserves become exhausted, the systolic performance of the ventricular pump is altered and becomes extremely dependent upon the systolic constraints which are then increased. It may be difficult to take into consideration an insufficiency of the contractility of the ventricular muscle in front of clinical signs of cardiac insufficiency which is conditioned by abnormalities in the filling of the ventricular pump. In addition, some "pathological" hyperthophies may secondarily induce an alteration of the intrinsic properties of the muscle (during its contraction, relaxation an/or extension), susceptible to induce or aggravate a ventricular insufficiency. The causes remain uncertain, since a metabolic imbalance of the myocardium by increase of the needs as well as a decrease of the coronary reserve and the exchange capabilities are commonly accepted. What are the mediators of these mechanisms of quantitative, geometric adaptation and also--at least in some animals--structural adaptation (isoenzymes of myosin)? Why do they seem, at times, strangely absent or quickly out-of-date, or sometimes excessive, with all the drawbacks specific to hypertrophy? The answer to these questions would perhaps represent a new therapeutic approach to left ventricular insufficiency.
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PMID:[Left ventricular hypertrophy. Advantages and drawbacks]. 295 Aug 20

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

According to Meerson, the adaptation to cardiac overload can be divided into three periods: the first stage, immediately after the initiation of the defect during which hypertrophy develops, followed by the stable hypertrophy phase (SHP), and a third phase of myocardial failure. Ventricular muscle contraction during SHP has been extensively studied both in vivo and in vitro with conflicting results. In isolated papillary muscles, most studies showed a normal or depressed contractility during chronic volume overload and a depressed inotropic state in pressure overload with a reduced maximal velocity of shortening which has been related to a myosin isozyme shift. In contrast, in conscious animals, haemodynamic status is usually described as preserved during SHP with a ventricular hyperfunction and a normal contractile function per unit of muscle. This was the basis of the concept of preload reserve and afterload mismatch described by Ross. However, mechanisms other than preload reserve may play a role during cardiac adaptation to pressure or volume overload. For instance, we recently showed in the early phase of pressure overload an increased inotropic state of the in situ heart with a change of the excitation contraction coupling evidenced by a modification of the force-frequency relations. Changes in the adrenergic receptors (density and/or affinity) may also contribute to the adaptation of the in situ heart to cardiac overload. They represent an important research area because they may explain, along with species and model differences, the discrepancies between in vivo and in vitro studies.
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PMID:Mechanical adaptation to chronic pressure overload. 296 12

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


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