Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of FK506 for 15 days at daily doses of 3.2 mg/kg p.o., 10 mg/kg p.o., 0.32 mg/kg i.m., or 1 mg/kg i.m. to heart-allografted rats resulted in a significant prolongation of graft survival time. The best graft acceptance was obtained in the 1 mg/kg i.m. group: all six grafts survived longer than 50 days, and two of them, indefinitely. The 31P nuclear magnetic resonance (NMR) technique was utilized to investigate in vivo the energy metabolism of grafts. The ratios of inorganic phosphate (Pi)/phosphocreatine (PCr) and PCr/ATP were useful parameters for monitoring cardiac insufficiency after transplantation. The mean ratios of Pi/PCr and PCr/ATP in syngeneic grafts were 0.38 +/- 0.11 and 1.88 +/- 0.42, respectively. In the control allografts, a rapid increase in the Pi/PCr ratio and a decrease in the PCr/ATP ratio were found from day 5. During the period of FK506 administration, increased Pi/PCr and decreased PCr/ATP ratios were also observed in all groups. The changes in these ratios were related with FK506 dosage. The results suggest that FK506 has a side-effect on graft metabolism. The metabolism tended to improve upon cessation of the drug in all grafts, but it worsened again in 3-3 1/2 weeks in the rats treated with 3.2 mg/kg p.o., 10 mg/kg p.o., or 0.32 mg/kg i.m. This seemed to be due to graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:In vivo 31P nuclear magnetic resonance findings on heterotopically allografted hearts in rats treated with a novel immunosuppressant, FK506. 169 22

In patients with heart failure there are distinct functional abnormalities in the myocytes themselves. This review deals with the deteriorations in the myocardial energy metabolism and the recently found alterations in the neurohumoral and hormonal signal transduction and signal realization within the cardiac cells. Beside the reduction in the volume of mitochondria in the overloaded myocardium the energy starvation is also reflected by a decrease in the content of high energy phosphates. Studies on nonfailing and failing human ventricular myocardium identified significant alterations in the neurohumoral regulation of the heart including the fluxes and the transport processes of Ca2+ as well as the beta-adrenoceptors, G-proteins, cAMP levels and cAMP-mediated processes. Recent data on the existence of auto-antibodies against the ADP/ATP translocator of the mitochondrial membrane and of stimulatory acting autoantibodies against i) the L-type calcium channel and ii) the beta 1-adrenoceptor, respectively, in patients with dilated cardiomyopathy, may open a new view in the etiology of heart failure and for consequences in the therapeutic concept of these diseases.
 ...
PMID:[Cellular and molecular mechanisms in heart failure]. 172 87

In the present study: (a) physiopathology, (b) clinics, and (c) therapy of cardiothyreosis are discussed. (a) The hyperkinetic syndrome, the earliest clinical sign in thyrotoxicosis (vasodilatation, increase in inotropism, automatism, etc.), is mediated by a two-fold increase in the number of beta-receptors, and supported by an adequate synthesis of ATP and creatinphosphate (CP) in the young and, to a lesser extent, in the elderly. Genetical heart reserves are mobilized, thus significantly increasing the number and the size of mitochondria and also the enzymatic equipment (such as: the alpha-glycerophosphate-dehydrogenase, malic, pentosic cycles, etc.), a.s.o. Due to an excessive adrenergic action (glycogenolysis, an excessive oxygen consumption, up to necrosis, the ATP and CP syntheses dramatically drop; the phosphorus/oxygen ratio decreases to 2 (normal = 4). In this condition, the high functional cardiovascular performances are also impaired (the submaximal effort capacity is attained at a smaller and smaller oxygen consumption; Propranolol 2 mg i.v. decreased the cardiac output by above 30% (vs 10%--normal); electrocardiogram presents aspects of "coronary disease", tachycardia, etc.). An ultrastructural damage occurs: from "mitochondrial disease", partial lysis of myofibrils, to myofibrosis (revealed postmortem), in spite of a reduced degree of coronary atherosclerosis. Ultrastructural and biochemical experimental data support this point of view. (b) The incidence, precocity and severity of the thyrotoxic heart increase with age and the existence of a previous cardiovascular pathology. Cardiothyreosis is not present under 27 years; in 4,353 patients its incidence is of 25% (arrhythmia--21%, heart failure--12%, coronary insufficiency--1-3%). Of a major interest are tachyarrhythmias which may lead to a high mortality by hypodiastolic congestive heart failure, heart failure with secondary hyperaldosteronism, thromboembolic episodes and ventricular fibrillation. Thyrotoxicosis favours the disease of papillary muscles--mitral prolapse and insufficiency, reversible especially in children. (c) The treatment of thyrotoxic heart is an etiologic one (medical, surgical, radioactive--the last two being preferable after the adequate medical therapy). In particular, cardiothyreosis requires a reinforced irradiation (10,000 rads instead of 7,000 rads) in smaller 131I doses. The protection against the increased nocivity of catechols in thyrotoxicosis is very important (which explains the high mortality in the thyrotoxic "storm") and requires propranolol; doses above 2 mg/kilo body/day are recommended. In the elderly, the sensitivity to propranolol decreases: verapamil i.v. is more efficient in paroxysmal tachyarrhythmias (flutter, atrial fibrillation) and in those occurring intra-operatively during halothane narcosis. The anticoagulant therapy is administered in tachyarrhythmias with high ventricular rate, especially in the elderly, to avoid the embolic risk, higher in defibrillation condition.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Cardiothyreosis. 182 Oct 70

Changes in myocardial function, structure, high energy phosphates and lipid peroxide content were examined in hypertrophied hearts exposed to partially reduced forms of oxygen (PRFO) in an ex vivo system. Heart hypertrophy in rats was produced by narrowing of the abdominal aorta for 6, 12, 24, and 48 weeks. During this period, a stable hypertrophy and hyperfunction with no clinical signs of heart failure is reported to be accompanied by an increase in myocardial superoxide dismutase and glutathione peroxidase activities and a decrease in lipid peroxide content (Gupta and Singal, Circ. Res. 64:398-406, 1989). A 10-min perfusion of sham control hearts with PRFO caused a significant decline in the developed force, +/- dF/dt and a rise in resting tension. These changes due to PRFO were significantly less in all groups of hypertrophied hearts. PRFO produced 80.8 +/- 4.2% increase in malondialdehyde (MDA) content in sham controls, while different groups of hypertrophied hearts showed significantly lesser increase (range 45-50%) in MDA. PRFO resulted in loss of myocardial ATP and CP in control and hypertrophied groups, but this loss was significantly less in all groups of hypertrophied hearts. Both quantitative and qualitative ultrastructural changes due to PRFO were also found to be less in hypertrophied hearts. There were no significant differences among 6- to 48-week hypertrophy groups in their response to PRFO. The study suggests that endogenous antioxidants may serve as putative stabilizers of myocardial subcellular as well as contractile functions against oxidative stress.
 ...
PMID:Reduced myocardial injury due to exogenous oxidants in pressure induced heart hypertrophy. 183 11

31P nuclear magnetic resonance (NMR) was used to examine the metabolism of skeletal muscle in rats 6-8 wk after myocardial infarction (MI). These in vivo measurements were supplemented by measurement of creatine, phosphocreatine (PCr), and ATP in freeze-clamped muscle using high-performance liquid chromatography (HPLC) and assays of key muscle enzymes to better define the muscle abnormality observed in heart failure. Resting PCr/(PCr + Pi) and pH were similar in MI rats and controls. Rats with MI had lower pH and PCr/(PCr + Pi) than controls during sciatic nerve stimulation at 1 and 2 Hz. These changes were more severe in rats with large (greater than or equal to 46%) infarcts, and changes in pH and PCr/(PCr + Pi) were correlated with infarct size. Free [ADP] in vivo was estimated from the NMR and HPLC measurements. [ADP] was increased in rats with large infarcts during nerve stimulation, implying a defect in oxidative metabolism. Citrate synthase, a mitochondrial enzyme, was reduced in rats with large MI. Citrate synthase levels were correlated with changes in PCr/(PCr + Pi) at 2 Hz. The NMR changes in skeletal muscle can be explained by reduced oxidative capacity of skeletal muscle, and this proposition is supported by the demonstration of reduced citrate synthase levels in skeletal muscle of rats with large infarcts.
 ...
PMID:Skeletal muscle metabolism in heart failure in rats. 187 70

In recent years, the use of thrombolytic therapy for the treatment of acute myocardial infarction has become the standard of care. A new phenomenon known as "stunned" myocardium has been described with the use of this treatment. Stunned myocardium refers to tissue that has been reperfused before of necrosis, but that remains dysfunctional. Stunned myocardium can regain its contractile function at any time from several hours to two weeks following reperfusion. It is important for nurses to understand this phenomenon and to incorporate this knowledge in the care of patients in the coronary care unit. Mechanisms that cause stunned myocardium are poorly understood. Some theories include: (a) reduction of ATP levels, (b) coronary artery microvascular spasm or plugging, (c) cytotoxic injury from oxygen-derived free radicals and (d) abnormalities of calcium flux. Nurses need to understand the response of stunned myocardium to various cardiac drugs when caring for post-myocardial infarction patients exhibiting heart failure. It is important to be aware that contractile function may not be optimal for up to two weeks after reperfusion.
 ...
PMID:The phenomenon of "stunned" myocardium: implications for coronary care nurses. 208 51

The prolonged noradrenaline treatment of rats (total dosage from 1 week--25 mg/kg), results in greatly reduced cardiac pump function and heart rate with a pronounced increase in left ventricular diastolic stiffness. These functional changes are associated with a deficiency of energy supply, especially depletion of phosphocreatine content. The taurine administration (100 mg/kg prior to 20 min noradrenaline injection) is accompanied by reliably less essential cardiac insufficiency. Moreover, the ATP, ADP level is normal and phosphocreatine content enhances by 15%.
 ...
PMID:[Norepinephrine-induced heart failure and the protective effect of taurine]. 208 93

Early reports have attributed cardiac failure during acute and chronic models of shock to peripheral vascular dysfunction and decreased venous return. More recently interest has focused on the heart as a primary target responsible for cardiovascular changes associated with acute endotoxin or hemorrhagic shock. At present, it remains controversial whether the heart fails early following the induction of experimental hypodynamic shock. Data from our laboratory have shown that myocardial contractility was increased early following acute endotoxin and splanchnic artery occlusion shock, and it was not until the agonal or terminal phase that contractility was depressed. We have used the slope of the left ventricular pressure-dimension relationship (Ees) as our index of contractile function. This technique is preferential since it is not affected by changes in the loading conditions on the heart. Unlike most reports that have used LV dP/dt as an index of contractility in the intact animal, we have shown that Ees and LV dP/dt do not uniformly reflect changes in contractility. LV dP/dt and related measures do, however, reflect the overall global changes in myocardial performance, which are affected by changes in preload, afterload, heart rate, and contractility. The reductions in LV dP/dt therefore mainly reflect the changes in arterial blood pressure associated with acute hypodynamic shock. The increase in contractility reported during endotoxin shock were shown to be induced by stimulation of beta-adrenergic receptors--when the beta-blocking drug, propranolol, was given to animals during shock, contractility decreased. The mechanism(s) responsible for the failure of the heart during the late or agonal periods of shock is (are) unknown. We have shown in dogs who die as a result of endotoxin shock that the hearts exhibit a progressive energy deficit, whereas animals surviving the experimental protocol maintained levels of ATP and creatine phosphate. It is unclear if the changes in high-energy phosphates during endotoxin shock cause irreversibility. Other potential mediators of cardiac failure have included ischemia/hypoxia, toxic myocardial depressant factors, deterioration of sympathetic influences on the heart, electrophysiologic and ionic disturbances, etc. The relationship between these factors and failure of the heart in vivo during various shock paradigms remains to be elucidated.
 ...
PMID:When does the heart fail during shock? 213 82

To address the hypothesis that impaired ATP synthesis rates caused by changes in the creatine kinase system is an important mechanism underlying cardiac failure, we measured total creatine kinase activity, isoenzyme composition and creatine content in two animal models of hypertrophy with cardiac dysfunction, the spontaneously hypertensive rat in the transition to failure and the creatine-depleted hyperthyroid rat heart challenged by hypoxia. During the transition from stable compensated hypertrophy to failure characterized by decreased functional capacity, we found that total creatine kinase activity and particularly mitochondrial creatine kinase activity decreased. The decrease in functional capacity, the further increase in heart size and the derangements in the creatine kinase system did not occur if these animals were treated for 6 months with the antihypertensive agents, guanethidine or hydralazine. These results suggest that changes in the creatine kinase system occur coordinately with the transition to failure. To assess whether the changes in the creatine system may be causally linked to decreased functional capacity, we used 31P NMR spectroscopy of isolated perfused hearts to define the high energy phosphate content and cardiac performance of creatine-depleted (approximately 50%) hypertrophied hearts challenged by hypoxia. These hearts displayed greater susceptibility to hypoxic injury with regard to both systolic and diastolic function during and following hypoxia. We also measured total creatine kinase activity in right ventricular biopsy specimens from patients with various forms of cardiomyopathy and low ejection fractions, and found a positive correlation between total creatine kinase activity and ejection fraction. Taken together, these results support the hypothesis that decreasing the energy reserve for ATP synthesis renders the heart more susceptible to systolic and diastolic failure.
 ...
PMID:Energetic correlates of cardiac failure: changes in the creatine kinase system in the failing myocardium. 214 77

During hypoxic heart failure, inorganic phosphate (Pi) accumulates. We report the effects of Pi on force development and on myofibrillar ATPase-activity of human skinned atrial fibers, both at normal and at reduced levels of Mg-ATP. Pi (10 mM) depressed force production at maximal calcium activation (pCa 4.3) by about 40%. At higher pCa values (pCa 5.6), force inhibition was even more pronounced, but at low concentrations of Mg-ATP (10 microM), Pi was less effective. In contrast to contractile force, myofibrillar ATPase was only inhibited by about 10% at pCa 4.3, whereas it could be inhibited by 40-50% at submaximal calcium activation (pCa 5.6). As Pi inhibited contractile force more than ATPase activity, the ratio of ATPase-activity to force (tension cost) was increased by inorganic phosphate. ATPase-activity and tension cost were significantly reduced by lowering Mg-ATP concentration to 10 microM, whereas contractile force was less affected. Pi did not affect ATPase under these conditions at 10 mM Mg-ATP. Pi also shifted the calcium-force relationship towards higher Ca++ concentrations, that is, it decreased calcium sensitivity. In contrast, the calcium sensitivity of myofibrillar ATPase was less affected. These findings suggest that inorganic phosphate may affect the myocardium by altering crossbridge kinetics rather than the calcium affinity of troponin-C. Because of its inhibitory effect on myofibrillar ATPase, inorganic phosphate may be partly cardioprotective in the hypoxic myocardium. However, this "energy sparing' effect is probably offset by the greater "tension cost' that decreases the "efficiency' of tension maintenance in the presence of inorganic phosphate.
 ...
PMID:Inorganic phosphate inhibits contractility and ATPase activity in skinned fibers from human myocardium. 214 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>