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)

When rat hearts were subjected to abrupt hypoxia the onset of NADH changes as measured by epicardial fluorescence and of depressed contractility occurred at similar times. Direct measurements of changes in tissue metabolism lagged behind changes in fluorescence and contractility. Calculated NAD:NADH ratios became reduced more rapidly and to a greater extent in the cytoplasm than in the mitochondria, but did not necessarily signal greater changes in total NADH. The detection of depressed contractility before a fall in intracellular pH or a rise in intracellular lactate casts doubt on the postulate that an increase in hydrogen ion is the primary cause of hypoxic myocardial failure.
 ...
PMID:Early changes in myocardial hypoxia: relations among mechanical function, pH, and intracellular redox states. 0 55

Acute teste staged on rats showed low doses of the cardiac glycoside isolanide to bring down the level of total lipids, cholesterol and beta-lipoproteins, without causing any changes in the content of NAD, adenyl nucleotides, non-esterified fatty acids (NEFA) and of phospholipids in themyocardium. Large doses of the drug uniformly reduce the content of all the co-enzymes fractions, the amount of ARP, ADP, cholesterol, beta-lipoproteins and the raise the level of total lipids, phospholipids and NEFA. In cases of acute cardiac insufficiency the drug produces a normalizing action on the co-enzymes and adenyl nucleotides content and reduces that of beta-lipoproteins and cholesterol. It appears that a definite part in the mechanism of the isolanide action plays its influence on the level of nucotinamide co-enzymes, adenyl nucleotides and lipids.
 ...
PMID:[Action of isolanide in acute cardiac insufficiency in rats]. 92 75

The aim of the present study was to investigate whether or not alterations of Gs alpha can be detected with cholera toxin-induced ADP-ribosylation in myocardial membranes from patients with heart failure. Therefore, Gs alpha was radiolabeled by cholera toxin-catalzyed (32P)ADP-ribosylation with (32P)NAD as substrate. In membranes from left ventricular myocardium of six patients with dilated cardiomyopathy classified as NYHA IV and three samples from two non-failing donor hearts, labeling was too weak to allow detection of possible changes in the amount of Gs alpha. Therefore, the cytosolic small molecular weight G protein ARF (ADP-ribosylation factor), a cofactor for cholera toxin-induced ADP-ribosylation of Gs alpha, was partially purified from bovine cerebral cortex. ARF activity was quantified by its ability to enhance auto-ADP-ribosylation of cholera toxin A1-subunit. Gs alpha was identified by comparing the ADP-ribosylation patterns of myocardial membranes, membranes prepared from human leukemia (HL 60) and S 49 mouse lymphoma wild type cells (45 kDa-band present) with membranes of the Gs alpha-deficient S 49 variant cyc- (45 kDa-band missing). In the presence of ARF, specific radiolabeling of the Mr 45,000 subtype of Gs alpha was markedly enhanced. The amounts of Gs alpha as measured by cholera toxin-dependent (32P)-ADP-ribosylation in the presence of ARR were similar in failing and nonfailing human hearts. It is concluded that factors other than Gs alpha are responsible for the altered regulation of the adenylate cyclase complex in heart failure. Moreover, by enhancing cholera toxin-catalyzed ADP-ribosylation, endogenous ADP-ribosylation factor from bovine brain appears to be a useful tool to study Gs alpha even in tissues in which the labeling of Gs alpha is rather weak.
 ...
PMID:Improvement of cholera toxin-catalyzed ADP-ribosylation by endogenous ADP-ribosylation factor from bovine brain provides evidence for an unchanged amount of Gs alpha in failing human myocardium. 210 80

The activity of human myocardial enzymes in sudden coronary death (SCD) was quantitatively histochemically examined. The activity of succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), beta-oxybutyrate dehydrogenase (beta-OBDH), alpha-glycerolphosphate dehydrogenase (alpha-GPDH), NAD-diaphorase (NAD-ase), and glucose-6-phosphate dehydrogenase (G-6-PDH) was measured on prompt autopsies (up to 3 hours of death onset). beta-OBDH and LDH showed an increase in activity in the myocardium from the subjects who had suddenly died from coronary heart disease without evident changes in the heart. In SCD in the presence of small cardiosclerosis, the activity of the enzymes characterizing the major processes of energy generation was also enhanced, which was caused by moderately severe myocardial hypertrophy. In the myocardium from the subjects who had died from coronary heart disease in the presence of large postinfarction cardiosclerosis, the activity of the enzymes was directly related to the degree of myocardial hypertrophy and the signs of chronic heart failure. As myocardial hypertrophy progressed, the enzymatic activity rose, but there were signs of chronic heart failure, it fell. The findings suggest that the changes in myocardial enzymatic activity in SCD are heterogeneous and associated with the type of prior abnormalities in the cardiovascular system.
 ...
PMID:[Disorders of myocardial metabolism in sudden coronary death in the presence of coronary atherosclerosis: findings of quantitative histoenzymologic studies]. 221 37

Glycolysis is slow in the heart, especially in the cardiomyopathic heart. Glycolysis is partially rate-limited by phosphofructokinase (PFK), an enzyme which is inhibited by calcium (Ca2+)i and hydrogen ions (H+)i and activated by cAMP. (H+)i and (Ca2+)i are augmented in cardiomyopathy. With glucose as the only substrate (NADH)/(NAD) the phosphorylation potential and developed pressure were significantly lower, and concentrations of phosphomonoester sugars and hydrogen ions (H+)i were significantly higher in isolated cardiomyopathic hearts as compared to healthy hamster hearts. Pyruvate lowered diastolic (Ca2+)i in cardiomyopathic hamster hearts. With pyruvate as the substrate (NADH)/(NAD), the phosphorylation potential and developed pressure increased significantly and concentrations of phosphomonoester sugars (PME), (H+)i and diastolic (Ca2+)i decreased significantly in myopathic hamster hearts. The results suggest that late heart failure in the myopathic hamster is associated with calcium and/or hydrogen ion-induced inhibition of glycolysis.
 ...
PMID:Glycolysis in heart failure: a 31P-NMR and surface fluorometry study. 224 66

Enzymes in the human myocardium following sudden death were examined for activity in a quantitative histoenzymological study, these were NAD-dependent dehadrogenases of succinate (SDG), lactate (LDG), beta-hydroxybutyrate (beta-HOBDG), alpha-glycerophosphate (alpha-GPDG), alcohol (ADG), glucoso-6-phosphate (G-6-PDG), and NAD-diaphorase (NADse), and catalase. Autopsies were performed within 3 h after death. beta-HOBDG and LDG were found to show an increase in activity in the cardiomyocytes of sudden death subjects with coronary heart disease without apparent changes. In the myocardium from death subjects with coronary heart disease and large postinfarct cardiosclerosis, the activity of the enzymes was directly related to the severity of myocardial hypertrophy and signs of chronic heart failure. As myocardial hypertrophy developed, the enzyme activity increased; when there appeared signs of chronic heart failure it decreased. The myocardium from sudden death subjects with alcoholic cardiomyopathy showed diminished redox enzyme activity and higher activity of the enzyme utilizing alcohol (ADG and catalase). The findings suggest that changes in the enzyme activity in the myocardium are of various type and depend on previous cardiac abnormalities.
 ...
PMID:Quantitative histoenzymological characteristics of the myocardium in sudden cardiac death. 252 98

Quantitative histochemical assays of several enzymes (succinic, lactic, beta-hydroxybutyrate, alpha-glycerophosphate, and glucose-6-phosphate dehydrogenases, NAD diaphorase, and phosphorylase) in the myocardium of persons who had died suddenly with postinfarctional cardiosclerosis have failed to reveal any changes specific for this patient group. Direct correlations were established between the enzyme activities assayed, on the one hand, and the extent of myocardial hypertrophy and the signs of chronic heart failure, on the other. The activities of beta-hydroxybutyrate dehydrogenase and glucose-6-phosphate dehydrogenase, which are involved in fatty acid utilization and in the pentose phosphate pathway, were elevated in cases of moderate hypertrophy, as were those of all redox enzymes in cases of strongly marked hypertrophy, although they were reduced in cases with signs of chronic cardiac failure despite the presence of considerable myocardial hypertrophy. Areas of acute myocardial ischemia were discovered in 45% of the cases.
 ...
PMID:[Histochemical study of the enzyme activity of the myocardium of sudden death victims with postinfarct cardiosclerosis]. 296 Feb 98

Alterations in the level and function of the stimulatory guanyl nucleotide binding protein (Gs) from the cardiac sarcolemma were examined in a canine model of heart failure. The present study is based on our previous investigations that demonstrated both a loss of beta-adrenergic agonist high-affinity binding sites and a decreased adenylate cyclase activity in sarcolemma from failing hearts. Using cholera toxin and [32P]NAD, we labeled the alpha subunit of Gs (Gs alpha) and found a 59% reduction in the level of this protein. Further, a 50% reduction in Gs activity was noted in a reconstitution assay utilizing membranes from the mouse S49 lymphoma cell line cyc-, which is deficient in Gs. These data suggest that, in this model of pressure-overload left ventricular failure, the acquired defect in the beta-adrenergic receptor/adenylate cyclase system involves a deficiency in the coupling protein Gs. Such an abnormality may explain the decreased adrenergic responsiveness of the failing left ventricle.
 ...
PMID:Decreased stimulatory guanosine triphosphate binding protein in dogs with pressure-overload left ventricular failure. 312 20

We studied peripheral skeletal muscle metabolism in monocrotaline-treated rats. Two distinct groups emerged: a percentage of the animals developed ventricular hypertrophy, with no signs of heart failure (compensated group), whilst others, besides ventricular hypertrophy, developed the syndrome of congestive heart failure (CFH group). Oxidative metabolism and redox cellular state were expressed in terms of creatine phosphate, purine (ATP, ADP and AMP) and pyridine (NAD and NADH) nucleotides tissue content. Skeletal muscles with different metabolism were studied: (a) Soleus (oxidative), (b) extensor digitorium longus (glycolytic) and tibialis anterior (oxidative and glycolytic). The results showed that in CFH animals a decreased high-energy phosphates content occurs in the soleus and extensor digitorum longus, but not in the tibialis anterior. In the soleus. ATP declined from 20.31 +/- 2.5 of control group to 9.55 +/- 0.61 mumol/g dry wt. while in the extensor digitorum longus ATP declined from 30.92 +/- 2.68 to 22.7 +/- 1.54 mumol/g dry wt. In both these muscles, a shift of NAD/NADH couple towards oxidation was also observed (from 26.58 +/- 3.34 to 6.95 +/- 0.97 and from 18.88 +/- 3.43 to 10.57 +/- 1.61, respectively). These alterations were more evident in the aerobic soleus muscle. On the contrary, no major changes occurred in skeletal muscle metabolism of compensated animals. The results show that: (1) a decrease in muscle high-energy phosphates occurs in CFH; (2) this is accompanied by a decrease of NAD/NADH couple suggesting an impairment in oxygen utilization or availability.
 ...
PMID:Skeletal muscle metabolism in experimental heart failure. 893 80

This paper reviews the model of the control of mitochondrial substrate oxidation by Ca2+ ions. The mechanism is the activation by Ca2+ of four mitochondrial dehydrogenases, viz. glycerol 3-phosphate dehydrogenase, the pyruvate dehydrogenase multienzyme complex (PDH), NAD-linked isocitrate dehydrogenase (NAD-IDH) and 2-oxoglutarate dehydrogenase (OGDH). This results in the increase, or near-maintenance, of mitochondrial NADH/NAD ratios in the activated state, depending upon the tissue and the degree of 'downstream' activation by Ca2+, likely at the level of the F1Fo ATPase. Higher values of the redox span of the respiratory chain allow for greatly increased fluxes through oxidative phosphorylation with a minimal drop in protonmotive force and phosphorylation potential. As PDH, NAD-IDH and OGDH are all located within the inner mitochondrial membrane, it is changes in matrix free Ca2+ [Ca2+]m which act as a signal to these activities. In this article, we review recent work in which [Ca2+]m is measured in cells and tissues, using different techniques, with special emphasis on the question of the degree of damping of [Ca2+]m relative to changes in cytosol free Ca2+ in cells with rapid transients in cytosol Ca2+, e.g. cardiac myocytes. Further, we put forward the point of view that the failure of mitochondrial energy transduction to keep pace with cellular energy needs in some forms of heart failure may involve a failure of [Ca2+]m to be raised adequately to allow the activation of the dehydrogenases. We present new data to show that this is so in cardiac myocytes isolated from animals suffering from chronic, streptozocin-induced diabetes. This raises the possibility of therapy based upon partial inhibition of mitochondrial Ca2+ efflux pathways, thereby raising [Ca2+]m at a given, time-average value of cytosol free Ca+2.
 ...
PMID:Role of mitochondrial calcium transport in the control of substrate oxidation. 974 30


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