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)

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

1. The gastrocnemius muscle of seven patients with mild to moderate chronic heart failure and of five healthy control subjects was studied using 31P nuclear magnetic resonance spectroscopy. Spectra were collected at rest and during an incremental, symptom-limited, exercise protocol. Blood flow was measured in the same study during brief interruptions to exercise. 2. The phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio was lower in patients with heart failure than in control subjects at an exercise rate of 1.5 W, although intracellular pH and blood flow were similar. 3. The cytosolic free adenosine 5'-diphosphate concentration was markedly increased in patients with heart failure exercising at 1.5 W compared with control subjects exercising at the same workload. 4. Although the maximum workload achieved by patients with heart failure was less than half of that reached by control subjects, the pH and the phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio were lower in patients with heart failure at maximal load. Blood flow was less at maximal exercise in patients with heart failure than in control subjects in keeping with the reduced work load. 5. The phosphocreatine depletion induced in the gastrocnemius muscle by exercise was more severe than previously described in the forearm of patients with heart failure. 6. Metabolic abnormalities in skeletal muscle may contribute to exercise intolerance in heart failure, particularly during submaximal exercise.
 ...
PMID:Skeletal muscle metabolism in heart failure: a 31P nuclear magnetic resonance spectroscopy study of leg muscle. 217 44

Cardiac failure and skeletal muscle weakness are the main clinical features of glycogenosis type II, a lysosomal storage disorder caused by acid alpha-glucosidase deficiency. In our study, we have investigated in a rat heart perfusion-recirculation system whether acid alpha-glucosidase can be taken up from the vascular system into cardiomyocytes. When rat hearts were perfused with mannose 6-phosphate-containing acid alpha-glucosidase purified from bovine testis, a 3- to 4-fold increase of enzyme activity was obtained. Perfusion with human placental acid alpha-glucosidase not containing the mannose 6-phosphate recognition marker did not have such an effect. The presence of bovine testis acid alpha-glucosidase in heart tissue was demonstrated by immunoblotting. Immunocytochemistry provides evidence for uptake of the exogenous enzyme in lysosomes of the cardiomyocytes. The relevance of these findings for enzyme therapy in glycogenosis type II is discussed.
 ...
PMID:Rat heart perfusion as model system for enzyme replacement therapy in glycogenosis type II. 223 32

The numerous metabolic abnormalities encountered in chronic purgative abusers were investigated and the new concept of autonomous pseudo-Bartter's syndrome documented. Detailed metabolic screening tests were performed in 9 women aged 17-54 years. Two patients underwent further studies, including serum renin and aldosterone, blood volume, total body potassium, urinary chloride and prostaglandin determinations, and each underwent renal biopsy on admission and after 1 year free from laxative abuse. Clinical complications included confusion, convulsions, coma, skeletal muscle weakness with or without paralysis or rhabdomyolysis, cardiac failure, urinary tract infections and bone disease (osteomalacia, secondary hyperparathyroidism and osteoporosis). Hypokalaemia, hypomagnesaemia, hypocalcaemia and hypophosphataemia were frequent findings. Serum creatine kinase correlated inversely with the product of the potassium and serum phosphate (r = -0.86; P less than 0.03), suggesting that hypokalaemia and hypophosphataemia act synergistically to produce muscle damage. After laxative withdrawal, oedema and weight gain, followed by diuresis, ensued in 7 patients. In the other 2, ongoing chloruresis, kaliuresis, hyper-reninaemia and raised urinary prostaglandin secretion persisted. Renal biopsies in these 2 patients showed the features of juxtaglomerular apparatus hyperplasia as well as medullary interstitial cell hyperplasia. In conclusion, pseudo-Bartter's syndrome was documented in 9 chronic laxative abusers. Because patients often indulged in more than one aberrant habit, e.g. laxative and/or diuretic abuse or bulimia, the clinical syndrome produced a myriad of confounding metabolic derangements, which we termed 'metabolic madness'. Laxative withdrawal was complicated by temporary pseudo-idiopathic oedema, which persisted in 2 patients. Further studies in these 2 women strongly supported the concept of 'autonomous pseudo-Bartter's syndrome'.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Chronic laxative abusers with pseudo-idiopathic oedema and autonomous pseudo-Bartter's syndrome. A spectrum of metabolic madness, or new lights on an old disease? 225 4

There is controversy as to whether potent inotropic agents are beneficial or detrimental in moderate to severe heart failure. Accordingly, we studied the effects of amrinone, amrinone plus dobutamine, and dobutamine alone on mechanical performance, myocardial oxygen consumption, and high energy phosphate metabolism in different stages of congestive heart failure in the cardiomyopathic Syrian hamster. In hearts with moderate heart failure, administration of amrinone, amrinone plus dobutamine, and dobutamine alone increased developed pressure significantly, whereas the phosphorylation potential increased significantly only with amrinone and amrinone plus dobutamine. In hearts with advanced heart failure, administration of amrinone and amrinone plus dobutamine increased developed pressure significantly, whereas dobutamine alone had no effect. The phosphorylation potential improved significantly only with amrinone. Thus, amrinone improved mechanical performance and mitochondrial activity in both heart failure states. Dobutamine potentiated amrinone's beneficial effects in moderate heart failure, but negated the positive inotropic effect of amrinone in advanced heart failure. Therefore, hearts responded differently to potent inotropic agents depending on the severity of heart failure.
 ...
PMID:Dobutamine potentiates amrinone's beneficial effects in moderate but not in advanced heart failure. 31P-MRS in isolated hamster hearts. 230 5

Dobutamine is known to increase leg blood flow during exercise in patients with heart failure. However, it is uncertain whether the increased flow is delivered to working skeletal muscle. In 7 patients with heart failure, the effects of dobutamine were examined on calf phosphorus-31 magnetic resonance spectroscopy (MRS) spectra and femoral vein blood flow during rest and upright plantar flexion. During upright plantar flexion every 3 seconds, dobutamine increased femoral venous blood flow (control 1.7 +/- 0.1; dobutamine 2.1 +/- 1.0 liters/min; p less than 0.05) and increased femoral venous O2 saturation (control 24 +/- 5%; dobutamine 31 +/- 2%; p less than 0.05), indicating improved total leg blood flow. However, dobutamine did not change the slope of the relation between systemic VO2 and the calf inorganic phosphate to phosphocreatine relation (control 0.0054 +/- 0.0039; dobutamine 0.0056 +/- 0.0032; difference not significant) and did not change muscle pH, suggesting no improvement in blood flow to active skeletal muscle. These findings suggest that dobutamine does not improve oxygen delivery to working skeletal muscle in patients with heart failure, despite its ability to increase cardiac output and limb blood flow.
 ...
PMID:Effect of dobutamine on skeletal muscle metabolism in patients with congestive heart failure. 233 Aug 98

A 38-year-old man with a colonic carcinoma experienced cardiogenic shock during continuous intravenous treatment with 5-fluorouracil (5-FU), without clinical or electrical signs of coronary insufficiency and with a normal coronary angiogram. His symptoms resolved after eight days of inotropic and vasodilator therapy. Because of the severity of the shock, rechallenge was not performed. This is the first case of acute cardiac failure without coronary ischemia, associated with 5-FU monotherapy. Experimental studies suggest that this adverse effect could be due to myocardial accumulation of 5-FU leading to depletion of high energy phosphate compounds. This might also explain the more frequently seen acute coronary insufficiency due to 5-FU.
 ...
PMID:Acute myocardiotoxicity during 5-fluorouracil therapy. 235 81

The possibility of exploiting the cardiovascular and renal action of dopamine for therapeutic purposes is enhanced by its conversion into orally active prodrugs. Following an outline of the medicinal chemistry bases of the development of these prodrugs, laboratory and clinical pharmacology of ibopamine, levodopa, gludopa, and TA-870 are reviewed, pointing out the interesting indications of various preliminary studies in heart failure, essential hypertension, and renal failure on the one hand, and the extensive therapeutic experience with ibopamine as an "inodilator" in the chronic treatment of congestive heart failure on the other hand. New experimental results are also reported for ibopamine and for the novel prodrug Sim 2055, i.e., epinine-4-O-phosphate. The latter is shown to act as a selective renal vasodilator on oral administration in dogs and it is therefore proposed for clinical investigation in renal failure and in essential hypertension.
 ...
PMID:Cardiovascular and renal action of dopaminergic prodrugs. 248 41

Pre-dialysis plasma oxalate concentration was measured in a cross-sectional study of 75 patients receiving maintenance haemodialysis. The aims of this study were to enable formulation of hypotheses regarding the determinants of plasma oxalate concentration and to allow preliminary examination of the possibility that hyperoxalaemia confers an increased risk of cardiac and vascular disease even in the absence of primary hyperoxaluria. Plasma oxalate concentration ranged between 7 and 76 mumol/l, mean (SD) 34.6 (18.1) mumol/l (normal range less than 0.8-2.0 mumol/l). Significant correlations were found between plasma oxalate concentration and plasma creatinine, duration of dialysis, current dose of ascorbic acid, and serum phosphate, and each of these variables retained significance on multiple linear regression. Oxalate clearance across a 1 m2 hollow-fibre Cuprophan dialyser, at 500 ml/min dialysate flow and blood flow between 175 and 225 ml/min, was measured 1 h after commencement of dialysis (n = 19). Mean (SD) clearance was 96.5 (27.0) ml/min. No significant association was found between self-reported maximum walking distance or the occurrence of symptoms of cardiac failure and plasma oxalate concentration. No relationship was found between plasma oxalate concentration and electrocardiographic conduction disturbances (n = 8) 'major' ST/T wave changes (n = 22), 'minor' ST/T wave changes (n = 49). Plasma oxalate was significantly greater in patients with radiologically detectable calcification of medium-sized arteries than in those without calcification, but duration of dialysis was also significantly longer in these patients. Routine haemodialysis results in marked hyperoxalaemia, which may be exacerbated by ascorbate supplementation. Oxalate clearance is similar to that of other small molecules such as creatinine and phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Plasma oxalate concentration, oxalate clearance and cardiac function in patients receiving haemodialysis. 251 11

The primary cause of death following i.v. injection of the basic phospholipase A2 (PLA2) from Naja nigricollis venom has been attributed to its direct cardiotoxicity. In view of our recent findings that cardiac failure caused by the basic PLA2 from Naja m. mossambica is primarily due to hyperkalemia resulting from cellular damage and possibly also from hemolysis, the cause of death due to the basic PLA2 from Naja nigricollis was re-investigated. In the anesthetized mice and rats, the PLA2 (0.3 micrograms/g, i.v.) produced a transient hypotension followed by recovery and subsequently by cardiac failure with ECG changes suggestive of hyperkalemia, such as P-R prolongation, tall T-wave, biphasic QRS-T complex, low voltage of QRS, A-V block, etc. Analysis of blood chemistry revealed marked increases in the plasma levels of K+, CPK, LDH, GOT, GPT, inorganic phosphate and hemoglobin (probably a mixture of hemoglobin and myoglobin). In the atrial preparation, however, no marked cardiotoxicity was observed except for a slight negative inotropic effect at 30 micrograms/ml. When 200 micrograms of the enzyme was injected into the coronary circulation in the Langendorff preparation, also no marked cardiotoxic effect was observed except for a decrease (about 40%) of coronary flow. From these results, it is concluded that the primary cause of death following i.v. injection of the basic PLA2 from Naja nigricollis is apparently cardiac failure due to hyperkalemia, resulting from cellular damage and possibly also from hemolysis, rather than direct cardiotoxicity.
 ...
PMID:Is direct cardiotoxicity the primary cause of death following i.v. injection of the basic phospholipase A2 from Naja nigricollis venom? 252 Mar 58


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