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

Overdoses of several volatile anesthetics (ether, chloroform, ethyl chloride, halothane, methoxyflurane) as well as of various barbiturates lead to severe contractile failure of the heart. In all cases it was found that at the stage of maximal failure the myocardial stores of ATP and phosphocreatine were increased, indicative of reduced high energy phosphate utilization. Barbiturate-induced failure can be fully reversed by the intravenous injection of CaCl2, isoproterenol, or strophanthin. Simultaneously ATP and phosphocreatine concentrations become normal. In contrast, cardiac failure caused by volatile anesthetics proved to be resistant to this therapy. Electron micrographs showed a normal structure of the transverse tubules in the case of barbiturate failure. On the other hand, after the application of volatile anesthetics, a striking dilatation of the transverse tubular system was observed. The irreversibility of this latter type of contractile failure is probably caused by permanent damage of myocardial ultrastructures involved in excitation-contraction coupling.
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PMID:Reversible and irreversible forms of contractile failure caused by disturbances by general anesthetics in myocardial ATP utilization. 118 70

By using biopsies, skeletal muscle metabolism was investigated in 22 patients with severe chronic heart failure. All the patients were in New York Heart Association functional class IV and constituted a subgroup of the previously published CONSENSUS trial. After this initial investigation of muscle metabolism in patients with chronic heart failure, the influence of the angiotensin converting enzyme inhibitor, enalapril, on skeletal muscle metabolism was studied by randomizing the patients in a double-blind manner to receive either placebo (n = 11) or enalapril (n = 11) in addition to conventional treatment. At the time of inclusion, the muscle content of energy-rich compounds, i.e. glycogen and the high energy phosphates, adenosine triphosphate (ATP) and phosphocreatine, was reduced as compared with healthy subjects and muscle lactate content tended to be higher than normal. Following study treatment, no significant changes occurred, neither within nor between the two subgroups. Thus, patients with severe chronic congestive heart failure display metabolic derangement in muscle, which, in this study, was not corrected by treatment with enalapril.
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PMID:Muscle energy metabolism in severe chronic congestive heart failure--effect of treatment with enalapril. 139 32

To determine whether cardiac hypertrophy secondary to chronic renovascular hypertension is associated with altered in vivo myocardial metabolism, phosphorus-31 nuclear magnetic resonance saturation transfer techniques were used to study creatine kinase (CK) kinetics in six chronically hypertensive dogs with moderate cardiac hypertrophy and eight control dogs. The forward rate constant of CK and the flux of phosphocreatine to adenosine triphosphate were determined in both groups of dogs before and during norepinephrine administration (1 microgram/kg per min), used to increase heart rate x systolic blood pressure (rate-pressure product), cardiac output and oxygen consumption. Baseline and norepinephrine-induced changes in rate-pressure product, cardiac output and oxygen consumption were similar in both groups of dogs, as were baseline forward rate constant and flux of phosphocreatine to adenosine triphosphate. However, the norepinephrine-induced changes in forward rate constant and flux were significantly less in hypertensive than in control dogs (p less than 0.05) even though changes in hemodynamic and functional variables were similar in both groups. These data demonstrate that moderate myocardial hypertrophy is associated with altered CK kinetics, which do not appear to affect the heart's ability for global mechanical recruitment at this stage in the hypertensive process. It is possible that the changes in myocardial enzyme kinetics may contribute to diastolic dysfunction previously reported in this model and may be a precursor for ultimate development of heart failure if hypertension is maintained for prolonged periods.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Creatinine kinase kinetics studied by phosphorus-31 nuclear magnetic resonance in a canine model of chronic hypertension-induced cardiac hypertrophy. 153 Aug 55

The development of 31P-nuclear magnetic resonance (NMR) has enabled direct and non-invasive measurements of muscle metabolism. Serial measurements of the phosphocreatine/inorganic phosphate (PCr/Pi) ratio, which is closely related to the adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio and pH during and after forearm exercise were performed in 11 patients with chronic lung disease (CLD), nine patients with chronic heart failure (CHF) and eight control subjects. As compared with control subjects, the PCr/Pi ratio in the patients with CLD or CHF was lower during the recovery period and significantly lower at three and 4 min exercise. The pH values after exercise were lower in patients with CLD or CHF compared to control subjects. The PCr/Pi ratio at 4 min after exercise in the patients with CLD or CHF did not correlate with parameters of cardiac function or arterial and mixed venous oxygen tension. The arterial oxygen content and output in patients with CLD and CHF were significantly lower than that of control subjects. Nutritional parameters were not statistically different among the three groups. These observations suggest that metabolic abnormalities may be present in the skeletal muscles of patients with CLD and CHF that are not due to under-nutrition. These may result from reduced arterial oxygen output and, partially, from physical detraining.
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PMID:31P-nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with chronic lung disease and congestive heart failure. 155 77

To investigate the effect of heart failure (HF) on skeletal muscle, gracilis, gastrocnemius, and triceps muscle histochemistry and enzyme activity, gracilis muscle performance, and gracilis muscle 31P magnetic resonance spectroscopy (MRS) metabolic responses to exercise were compared in six sham-operated control dogs (C) and seven dogs with HF produced by 3 mo of rapid ventricular pacing. HF reduced skeletal muscle weights and decreased type II fiber area (3,315 +/- 996 to 1,750 +/- 638 microns 2; P less than 0.01). Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activity also tended to decrease. Gracilis muscle inorganic phosphate-to-phosphocreatine ratios, oxygen uptake (VO2), and pH responses to exercise using supramaximal twitch stimulation, a form of exercise that produces maximal stimulation of all muscle fibers and therefore is independent of muscle mass, were similar in both groups. There was no significant difference in developed tension per gram muscle during stimulation at 0.5-200 Hz, maximal developed tension (C: 177 +/- 32 vs. HF: 173 +/- 44 g/g muscle), or muscle fatigability as assessed by percent of initial tension observed at the end of 2 min of 20 Hz stimulation (C: 52 +/- 17% vs. HF: 52 +/- 11%; all P = NS). These data suggest that HF produces skeletal muscle atrophy but that the remaining muscle exhibits normal performance and metabolism.
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PMID:Effect of heart failure on skeletal muscle in dogs. 156 18

Phosphorus-31 magnetic resonance spectroscopy can be used to study intracellular biochemistry non-invasively by measuring the relative proportions of high energy phosphates. Study of deteriorating cardiac metabolism might be useful in the management of hypertrophy and heart failure. 31P magnetic resonance spectroscopy was carried out in fourteen patients with aortic valve disease (six with aortic stenosis, eight with aortic incompetence). Six patients were receiving treatment for symptoms of heart failure. The phosphocreatine (PCr) to ATP ratio in these patients (1.1 [SD 0.32]) was significantly lower than that in thirteen controls (1.5 [0.2], p less than 0.001) or in the eight patients who did not have symptoms of heart failure (1.56 [0.15], p less than 0.0035). These findings indicate that heart failure in aortic valve disease is associated with low PCr, which could be due to loss of intracellular creatine. The measurement could eventually have a role in helping to determine the optimum timing for aortic valve replacement.
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PMID:Detection of low phosphocreatine to ATP ratio in failing hypertrophied human myocardium by 31P magnetic resonance spectroscopy. 168 42

We have developed a model for characterizing calcium handling by the intact cardiac sarcoplasmic reticulum (SR) that yields data consistent with both mathematical simulations of in situ SR Ca2+ uptake and deduced behavior of the Ca2(+)-induced Ca2+ efflux channels in mechanically skinned single cardiac cells. In Na(+)-based media (37 degrees C, pH 7.2, 50 mM Pi, 10 mM MgATP, pMg 3.3, 10 mM phosphocreatine), SR 45Ca2+ uptake by digitonin-lysed rat myocytes as a function of free [Ca2+] peaked at pCa 6.2, declined until pCa 5.6 and increased again at lower pCa. When Ca2(+)-induced Ca2+ efflux was inhibited with 30 microM ruthenium red and 10 mM procaine, uptake was saturable with a Vmax of 160 +/- 5 nmol.min-1.mg-1, K0.5 of 500 nM free [Ca2+] and slope factor of 1.6. In K(+)-based media, maximum Pi- and oxalate-supported uptake increased to 220 and 260 nmol.min-1.mg-1, respectively. Without phosphocreatine, 45Ca2+ uptake declined under all conditions; this was correlated with a decrease in ATP/ADP. Vmax for 45Ca2+ uptake was increased 20% in hyperthyroid myocytes but depressed 30% in myocytes from heart failure-prone rats. In canine myocytes, Vmax was the same as in normal rat cells, but K0.5 was 830 nM. Without efflux inhibitors, ryanodine caused a concentration-dependent decline in net Pi-supported 45Ca2+ uptake at pCa 6.3 (K0.5 = 1 microM), while 10 microM ryanodine depressed uptake at all pCa between 7.2 and 5.6. Ruthenium red/procaine fully reversed this effect.
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PMID:Calcium accumulation and release by the sarcoplasmic reticulum of digitonin-lysed adult mammalian ventricular cardiomyocytes. 169 80

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)
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PMID:In vivo 31P nuclear magnetic resonance findings on heterotopically allografted hearts in rats treated with a novel immunosuppressant, FK506. 169 22

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.
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PMID:Skeletal muscle metabolism in heart failure in rats. 187 70

Exercise intolerance is a major cause of morbidity in chronic heart failure (CHF) and has traditionally been attributed to skeletal muscle hypoperfusion during exercise. However, intrinsic abnormalities in skeletal muscle biochemistry and histology may also play an important role in the pathophysiology of exertional fatigue in CHF. Studies using 31P nuclear magnetic resonance (NMR) spectroscopy have demonstrated early skeletal muscle metabolic changes during exercise including excessive acidification and phosphocreatine depletion. Patients with CHF show muscle fibre atrophy with transformation of type I to II fibres accompanied by a decrease in oxidative enzyme capacity. Most of the drugs currently used to treat patients with CHF do not improve oxygen availability within exercising muscle or exercise capacity although some of them increase blood flow to skeletal muscle or alter the pattern of blood flow distribution. Physical training programmes improve exercise performance, ventilation, autonomic function and symptomatic status in CHF. Training can also increase cardiac output and reduce peripheral vascular resistance with concomitant increases in blood flow to exercising muscle and reduced arterial and venous lactate. 31P-NMR studies in patients with CHF have demonstrated significantly less acidification and phosphocreatine depletion during exercise after physical training. Animal studies suggest that the NMR changes in skeletal muscle of CHF depend on both the severity of heart failure and physical deconditioning, whereas training may reverse or prevent these alterations.
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PMID:Peripheral abnormalities in chronic heart failure. 192 83


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