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

The isolated perfused working rat heart preparation has been used to study the effects of respiratory acidosis on myocardial metabolism and contractilly. Hearts were perfused with 5 mM glucose and 10(-2) U/ml of insulin in order to enhance metabolsim of glucose relative to that of fatty acids. After perfusion with Krebs bicarbonate medium at pH 6.6, hearts rapidly ceased performing external work and peak left ventricular pressure fell by 75% after 5 minutes. Oxygen consumption, rate of ATP generation and overall glycolytic flux also declined rapidly. After about 2 minutes of perfusion, the fall of glycolytic flux showed a partial reversal, which was largely accounted for by increased lactate production, so that glucose oxidation decreased further. The reversal of glycoltic flux could be accounted for by partial release of H+ inhibition of phospho-fructokinase by increased tissue levels of adenosine 5'-diphosphate (ADP), adenosine monophosphate (AMP) and P1 and decreased levels of adenosine triphosphate (ATP) and creatine phosphate. The increased proportion of glucose uptake converted to lactate together with an increase of the tissue lactate/pyruvate ratio could be accounted for by inhibition of the malate-aspartate cycle combined with tissue hypoxia. Lactate accumulated in the tissue as a result of a decreased permeability of the plasma membrane to lactate. Decreased oxygen delivery to the myocardium was caused by secondary constriction of the coronary vessels. In further experiments, the coronary flow was regulated by an external pump which delivered fluid at a controlled rate into the aortic cannula above the coronary arteries, and the degree of tissue hypoxia was monitored by measuring changes of pyridine nucleotide reduction state by surface fluorescence techniques. The effects of acidosis uncomplicated by possible hypoxia were compared directly with those produced by ischemic hypoxia. The effects of acidosis under these conditions were similar to those described above, and to those produced by ischemia. From these and other data it is concluded that the effects of ischemia are caused by a lowering of the intracellular pH, which decreases the rate of energy production relative to the rate of energy demand. However, it is suggested that the primary cause of the decreased peak systolic pressure with either acidosis or ischemia is not a result of a defect of energy metabolism, but is due to alteration of the calcium cycle of the heart. Possible causes of irreversible heart failure after prolonged ischemia are discussed.
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PMID:Contribution of tissue acidosis to ischemic injury in the perfused rat heart. 0 93

The isolated isovolumic rat heart was used as a model of cardiac hypoxia. Force of cardiac contraction and cardiac cyclic nucleotide levels (cyclic GMP and cyclic AMP) were monitored in hearts subjected to hypoxia for 5 min and allowed to recover by reoxygenation. Hearts were obtained from both control animals and animals pretreated with methylprednisolone at 18 hr and 1 hr prior to sacrifice. Myocardial levels of cyclic GMP which were significantly (p less than 0.05) elevated above control during all periods of hypoxia were found to be lower when hearts were pretreated with methylprednisolone prior to hypoxic exposure. Hearts of animals pretreated with methylprednisolone also demonstrated better recovery during reoxygenation than did control hearts. These studies suggest that methylprednisolone may be beneficial in the prevention of myocardial failure following hypoxia via a modulation in myocardial cyclid GMP content.
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PMID:Possible role of cyclic nucleotides in the mechanism of the protective effect of methylprednisolone on the hypoxic rat heart. 21 63

Hearts from chronically adrenalectomized (ADX) cats deprived of any steroid support for 9-12 days were isolated and perfused in a Langendorff apparatus at a constant pressure of 95 mm Hg. The perfusion medium was Krebs-Henseleit buffer with either 10 mM glucose or 0.4 mM palmitate complexed to 3 percent albumin. Labeled 14C substrate was used and the transient rate of glucose and palmitate uptake was measured. Oxygen consumption and [14C] palmitate incorporation into CO2, and heart lipids were also measured. ADX hearts showed an enhanced glucose uptake rate compared with controls, 65 +/- 11.3 mumoles/gm to 16.2 +/- 6. However, the qO2 was not significantly different from control hearts. Palmitate uptake, O2 consumption, and 14CO2 were significantly lower in ADX hearts perfused with fatty acid as the energy substrate. Fatty acid uptake decreased from 9.7 +/- 1.0 to 3.6 +/- 1.1 and lipid fractions in the heart showed significant decreases in [14C] palmitate incorporated into triglycerides (p less than 0.001) and monoglycerides (p less than 0.01). The ADX heart does not appear to have any impairment to glucose uptake but does show an impairment to fatty acid uptake. Because the heart uses lipid as the primary energy source, the impairment probably is not the primary factor responsible for cardiac failure in adrenal insufficiency because of its capability of using other available substrates for energy.
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PMID:Glucose and palmitate uptake in the myocardium of isolated hearts from adrenalectomized cats. 125 83

Antioxidant enzyme activities, including superoxide dismutase, glutathione peroxidase and catalase, are known to be altered under various physiological and pathophysiological conditions. There is a significant increase in some of these activities in the myocardium during stable hyperfunctional heart hypertrophy subsequent to pressure overload, as well as after exercise training in rats. Hearts with increased antioxidant capacity have been reported to be more resistant to in vivo and in vitro oxidative stress. On the other hand, cardiomyopathy and heart failure under a variety of conditions are accompanied by increased free radicals and lipid peroxidation. These data lead to the hypothesis that maintained or improved function during compensated heart hypertrophy may be supported by an increased antioxidant capacity, and a relative deficit in this 'antioxidant reserve' may contribute in the decompensated state.
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PMID:A relative deficit in antioxidant reserve may contribute in cardiac failure. 213 50

Changes in oxygen radical mechanisms during 6-48 weeks of heart hypertrophy in rats subjected to a narrowing of the subdiaphragmatic aorta were examined. During this period, hypertrophied hearts demonstrated a stable hyperfunction, as indicated by an elevated but stable left ventricular systolic pressure, dP/dt, and aortic pressure and no change in left ventricular end diastolic pressure. Experimental animals showed increased heart-to-body weight ratios; however, the conventional signs of heart failure such as increased wet-to-dry weight ratios of liver and lung, ascites, or pleural effusion were absent. Hearts were examined for superoxide dismutase, glutathione peroxidase, and lipid peroxide activities. The superoxide dismutase activity was significantly higher in hypertrophied hearts at 6 and 12 weeks as compared with sham-operated rats (sham controls), while no difference was seen at 24 and 48 weeks due to a marked increase in the superoxide dismutase activity of sham control hearts in these age groups. During the period studied, glutathione peroxidase activity remained unchanged in controls but was significantly elevated in hypertrophied hearts. Lipid peroxide activity as indicated by the malondialdehyde content was significantly lower in hypertrophied hearts. Perfusion of isolated control and hypertrophy hearts with xanthine-xanthine oxidase, an exogenous source of oxygen radicals, resulted in contractile failure and rise in resting tension. In hypertrophied hearts, however, the contractile force was better maintained and there was a lesser rise in resting tension after exposure to xanthine-xanthine oxidase. The study suggests the development of a higher antioxidative capacity during the stable phase of hypertrophy due to a chronic pressure overload.
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PMID:Higher antioxidative capacity during a chronic stable heart hypertrophy. 252 64

Left ventricular (LV) contractile function and pump function were depressed in isolated working hearts from rats treated with either guanidinopropionic acid (GPA), an inhibitor of creatine influx, or the anthracycline antibiotic, adriamycin, for 6 and 10 weeks, respectively. In both groups of treated animals myocardial phosphocreatine content was lower than in control hearts, while ATP content was unchanged. Hearts of treated animals exhibited only a minor depression of cardiac output with a submaximal pressure load or during volume overload. However, at maximal pressure load GPA- and adriamycin-treated hearts performed 43% and 37% less pressure-volume work than control hearts. These changes were due both to decreased LV pressure development and diminished cardiac output. LV diastolic stiffness was significantly higher at the submaximal pressure load and the LV filling pressure area, which reflected LV filling, was lower in hearts of both treated groups. The differences in both indices were exaggerated when the maximal pressure load was applied. Limited LV filling due to incomplete myocardial relaxation appeared to represent the underlying cause of cardiac failure when afterload was increased. These results may be explained if adaptation of cardiac contractile function in some chronic cardiac diseases arises from a limited energy supply to the myofibrils.
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PMID:Adaptation of cardiac contractile function to conditions of chronic energy deficiency. 273 32

A review of 76 endomyocardial biopsies and 54 autopsies of patients with dilated cardiomyopathy (DCM) revealed features of hypertrophy and degenerative changes associated with long-standing hypertrophy. Long-term survivors had significantly heavier heart weights. Short-term survivors had heavier than normal right ventricular weights. No pathological findings supportive of a previous viral myocarditis, persistent slow virus infection or autoimmune process were observed. Hearts of autopsied DCM patients showed no significant difference from controls with regard to interstitial mononuclear cells. Morphometry failed to detect any difference in the fibrous tissue component between the DCM and control patients. Microscopic findings suggest that the cardiac failure of DCM is due to a potentially reversible functional abnormality. The cause of this is unknown, but the morphology suggests that future research should be directed by the premise that DCM represents a toxic-metabolic defect-deficiency state.
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PMID:Dilated (congestive) cardiomyopathy: a syndrome of severe cardiac dysfunction with remarkably few morphological features of myocardial damage. 315 40

Rats were fed a diet containing beta-guanidinopropionic acid (GP), an inhibitor of creatine transport. After 6 to 8 weeks of feeding the myocardial creatine (Cr) and phosphocreatine (PCr) stores were severely depleted while ATP content was normal. Hearts of GP-treated rats perfused according to Neely's working heart model revealed clear cardiac contractile failure: the maximal work capacity at a stepwise increase in resistance as well as the maximal oxygen consumption were 32 to 40% less in the GP group. The cardiac failure in GP-treated working hearts was associated with a rise in the left ventricular diastolic pressure, which could cause a diminished cardiac output probably due to impaired LV filling. The extent of the contractile failure was found to depend on functional load and on the degree of Cr (PCr) substitution. The energy fluxes through creatine kinase measured by the 31P-NMR saturation transfer technique were diminished by a factor of two after substitution of 90% of creatine, but still exceeded the rate of ATP turnover. The results are compatible with the concept of phosphocreatine pathway for intracellular energy transport and show that PCr is an important high energy phosphate compound for cardiac contractile function.
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PMID:The cardiac contractile failure induced by chronic creatine and phosphocreatine deficiency. 321 3

Experimental studies have documented that myocardial dysfunction is precipitated between 3 and 6 hr after endotoxin or E. coli. This finding has now been confirmed in human septic shock. A "Hinshaw-modified" isolated working left ventricle preparation has been used to document and assess the degree of failure. It was found that the failure is often severe and reversible only temporarily by adrenergic agents but reversible by digoxin or insulin. The cause of the failure has not been identified, but evidence is presented against a myocardial depressant factor (MDF) being the causative factor. Hearts subjected to a 2-4 hr period of hypotension on the threshold of failure show no signs of failure when subjected to blood circulating from an animal in splanchnic arterial occlusion shock. Hearts from pancreatectomized animals subjected to endotoxin shock with their source of MDF removed demonstrate the typical failure in 4-6 hr. Other factors are suggested that contribute to myocardial dysfunction: hypotension or nonuniform perfusion of subendocardial regions of the heart, depressed responsiveness to inotropic and chronotropic stimuli, intracardiac ionic and fluid disturbances, and increases in heart chamber and muscle stiffness. Since steroid/antibiotic therapy increases the probability (p less than 0.05) that an animal will survive lethal sepsis, investigating the effect of this therapy on myocardial function may aid in determining whether or not this degree of heart failure contributes in the animal to irreversible shock and death.
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PMID:Myocardial dysfunction in endotoxin- and E. coli-induced shock: pathophysiological mechanisms. 388 34

The effect of several phenothiazines on the extent of cellular damage resulting from the calcium paradox was examined. Hearts treated with trifluoperazine, a potent calmodulin inhibitor, exhibited less cellular damage than untreated myocardium as reflected by light microscopy, high-energy phosphate content and the loss of protein and creatine phosphokinase into the perfusate. A dose response of this effect revealed a maximal response at about 1 microM trifluoperazine, a concentration which lies well within the range generally attributed to calmodulin inhibition. Several other lines of evidence were also obtained suggesting a possible role for calmodulin in calcium-overload induced necrosis. First, the phenothiazines had little influence on membrane changes believed responsible for altered calcium permeability. Second, trifluoperazine was without major effect unless included in the reperfusion buffer, indicating that the drug is only effective during the phase associated with calcium overload. Finally, less protection was afforded hearts exposed to phenothiazines such as chlorpromazine and promethazine, which are weaker inhibitors of calmodulin, than those treated with the potent inhibitor trifluoperazine. While other interpretations are possible, these studies are consistent with a role for calmodulin in calcium overload-induced heart failure.
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PMID:Phenothiazine protection in calcium overload-induced heart failure: a possible role for calmodulin. 613 9


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