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

Organic nitrates were the first peripherally-active vasodilators to be used for the treatment of heart failure. Currently, three nitrate derivatives, glycerol trinitrate, isosorbide dinitrate and isosorbide 5-mononitrate as well as the nitrate-like substance molsidomine are employed clinically. For treatment of heart failure, the decisive hemodynamic effect is a meaningful reduction in ventricular filling pressures with maintenance or even a slight increase in cardiac output. The individual response to nitrates is variable. An important indicator for the effect achievable for a certain dose or for the necessary dosage to affect a defined reduction in ventricular filling pressures, is the magnitude of right atrial pressure. It can be assumed that the latter statement is also valid for the nitrate-like substance molsidomine. An inherent problem with any long-term treatment with nitrates is the incurrence of tolerance. This can be expected with any dosing regimen which leads to nitrate cumulation in the plasma or to nearly-constant, high, plasma concentrations as rendered by multiple daily administration of orally-active nitrates or with continuous transdermal or intravenous nitrate administration. The cause of nitrate tolerance is regarded as an insufficient or absent stimulation of guanylate cyclase and, consequently, inadequate generation of cyclic GMP due to availability of thiol substrate. Since the nitrate-like substance molsidomine appears to be able to stimulate guanylate cyclase independent of thiol groups, tolerance development may not be a limiting factor with this agent. Comparable reduction of diastolic pulmonary artery pressure after acute administration and at the end of one week of treatment with 4 mg molsidomine four times daily has been reported.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Nitrates in the treatment of heart failure]. 211 55

1. Skeletal muscle metabolism in chronic cardiac failure may be influenced by the many circulatory and neurohumoral adaptations in the condition. We investigated aerobic metabolism during exercise using indirect calorimetry in 15 patients with chronic cardiac failure and in 14 control subjects. Subjects exercised on a treadmill for 20 min at a steady-state submaximal workload. 2. Venous lactate levels were relatively constant throughout the exercise, although they were slightly greater in the patients with chronic cardiac failure than in the control subjects. The respiratory exchange ratio was lower in patients with chronic cardiac failure (0.777 +/- 0.021 vs 0.833 +/- 0.037, means +/- SD; P less than 0.0002, Mann-Whitney U-test). Relative fat utilization, expressed as a percentage of total energy expenditure, was therefore greater in patients with chronic cardiac failure (71.8 +/- 7.0 vs 54.1 +/- 12.3%, P less than 0.0005) and this was mirrored in a lower carbohydrate utilization (24.7 +/- 6.5 vs 43.3 +/- 12.1%, P less than 0.0002). Levels of free fatty acids, glycerol and noradrenaline were greater in patients with chronic cardiac failure. 3. We conclude that there is an increased reliance on fat, as opposed to carbohydrate, metabolism during exercise in chronic cardiac failure, and that this may relate to the elevated catecholamine and free fatty acid levels present. This may be a compensatory mechanism to preserve muscle glycogen stores, but as fat utilization is less efficient in terms of oxygen consumed, this shift may further impair exercise capacity.
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PMID:Substrate utilization during exercise in chronic cardiac failure. 216 96

In the acute neurosurgical setting, nonketotic hyperosmolar hyperglycemic coma (NHC) is thought to be caused by cerebral dehydration therapy and administration of steroids, glycerol, or mannitol. The mortality of this complication is reportedly very high, and is due to acute renal and/or cardiac failure. The authors evaluated the effect of low-dose dopamine (LDD; 1 to 5 micrograms/kg/min) administration in 10 patients with this syndrome. LDD was given to five patients. In these cases, hypovolemia was treated under central venous pressure monitoring with an iso-osmolar hyponatremic lactate solution given in a volume greater than the urine output. After the hypovolemia was corrected, the fluid was administered in a volume equal to the urine output until the serum osmolarity was normalized. In the five patients not given LDD, a large quantity of hypotonic solution was rapidly administered. In all patients treated with LDD, the urinary sodium increased and the urinary output stabilized. Consequently, the excess urea-nitrogen and serum sodium were quite easily washed out. The total net intake volume for the normalization of serum osmolarity was small and the duration of treatment was much shorter than that of patients not treated with LDD. The LDD regimen was not associated with complications, such as aggravation of cerebral edema, renal failure, or cardiac failure. On the other hand, three of the five patients not given LDD died of acute renal and/or cardiac failure without normalization of laboratory data. It is emphasized that this therapy, which results in beta-effect of catecholamine, sodium diuresis, and increased renal blood flow, is a practical means of managing acute neurosurgical cases complicated by NHC.
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PMID:[Low-dose dopamine treatment of patients in nonketotic hyperosmolar hyperglycemic coma]. 248 37

In the present paper, two experimental models of heart failure, namely hereditary cardiomyopathy in hamsters (BIO 14.6) and cardiac insufficiency due to mild (0.06 microM) isoprenaline overload of rabbit isolated perfused hearts, were compared in terms of resulting alterations at the level of the functionally isolated contractile system of detergent/glycerol treated skinned cardiac fibres. As the main features of Ca activation of tension in these models, the following were found: 1. Within the same species (RB hamsters, BIO 14.6 hamsters or rabbits), the Ca sensitivity, measured as pCa for half maximal Ca activation, was invariably higher in left than in right ventricular skinned fibres. 2. During the development of hereditary cardiomyopathy (BIO 14.6), maximum Ca-activated tension, measured per unit cross-sectional area, was reduced in an age-dependent manner, without any significant reduction in Ca sensitivity. This effect appeared to be more pronounced in left than in right ventricles. 3. In skinned fibres from right or left ventricular papillary muscles from in vitro isoprenaline pretreated rabbit hearts, no significant alteration in the maximum Ca-activated tension (per unit area) was observed in comparison to non-pretreated control hearts, whereas the Ca sensitivity was reduced. Treatment of control or failing heart skinned fibres with cAMP showed no additivity to the Ca desensitization induced by isoprenaline pretreatment. 4. Skinned fibres from isoprenaline pretreated left ventricular rabbit hearts showed a higher susceptibility to the Ca sensitizing effect of APP 201-533 than fibres from unpretreated control hearts. Mild isoprenaline overload and hereditary cardiomyopathy both are forms of heart failure which are presumably not associated with a lack of activator Ca. It is concluded that cardiotonic agents increasing the cardiac myofibrillar sensitivity to Ca ions would be beneficial in both cases, representing a phenomenologically causative treatment in hearts failing due to isoprenaline pretreatment. A main advantage over "classical" cardiotonic agents like cardiac glycosides, beta adrenergic stimulants or phosphodiesterase inhibitors would be the absence of the risk of drug-induced Ca overload.
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PMID:Heart failure and Ca++ activation of the cardiac contractile system: hereditary cardiomyopathy in hamsters (BIO 14.6), isoprenaline overload and the effect of APP 201-533. 282 79

Myosin form birefringence has been studied in cryostat sections of left ventricular myocardium from the dog and human. The muscle in such sections has been shown to demonstrate the sliding filament phenomenon. The sarcomere length of canine myocardium agreed with that found in comparable electron micrographs. Unexpectedly, it was found that glycerol, normally used as an inert and optically ideal mountant, caused profound change in myosin birefringence. This apparently invalidates results obtained with this mountant. The absolute birefringence found in these sections, whether mounted in glycerol or in an ATP-calcium buffer, corresponded to values found by other workers with skeletal muscle and isolated myosin. However, the birefringent properties (optical path difference: o.p.d.) of well functioning muscle was found to be low, the o.p.d. increasing when exposed to ATP and calcium. Poorly functioning muscle could be distinguished from well functioning muscle on the basis of its higher 'in air' o.p.d. This difference correlated well with physiological assessments of myocardial function or with clinical assessments of cardiac failure. Evidence is presented indicating that changes in apparent birefringence, caused by ATP-calcium or by anoxia, are due to altered orientation of the myosin micelles and can be inhibited by agents that inhibit myosin ATPase activity.
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PMID:Increased myosin orientation during muscle contraction: a measure of cardiac contractility. 383 15

Trabecular preparations from the hog heart right ventricle were "skinned" by treatment with Lubrol WX and glycerol. Ca++ activated isometric contractions were gradedly relaxed by inorganic phosphate (Pi) in the millimolar range or vanadate (Vi) in the micromolar range while tension cost (ATP split/force generated) was increased by a factor of 1.75. From measurements of force, ATPase activity, immediate stiffness and stretch activation, evidence is provided that the mechanical deactivation and the increase in tension cost may result from an acceleration of the myosin cross-bridge cycle, due to a direct interference of Pi and Vi with the chemomechanical energy transformation at the contractile proteins. The possible significance of such a mechanism in cardiac failure or muscle fatigue is discussed.
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PMID:Phosphate and vanadate reduce the efficiency of the chemo-mechanical energy transformation in cardiac muscle. 621 26

Two groups of Merino sheep were intoxicated separately and at different times with "gousiektebossie" (Pachystigma pygmaeum) until definite symptoms of heart failure were auscultated. Cardiectomy was carried out and some ventricular muscle from 1 group was stored in 50% glycerol at -20 degrees C for about 4 months. Natural actomyosin (n-actomyosin) was subsequently extracted and tested for magnesium, calcium and adenosine triphosphate (ATP)-dependent adenosine triphosphatase (ATP-ase) activity as well as for superprecipitation characteristics. Muscle strips were taken from the other group and stored for 2 weeks in 50% glycerol at -20 degrees C, whereafter it was analysed for an isometric tension-calcium response. The data showed no difference between gousiekte and control sheep in the sensitivity of the contractile system to the activating effect of calcium ions with respect to isometric tension development. A significant reduction of the magnesium dependent ATP-ase was found for gousiekte n-actomyosin in either the presence or absence of calcium ions. A depressed sensitivity for this enzyme to increasing concentrations of ATP in comparison to controls was also found ([ATP] less than 1 mM, [MgCl2] = 1 mM). No significant difference could be detected in the sensitivity of the n-actomyosin:ATP-ase system to magnesium. n-Actomyosin:ATP-ase of gousiekte hearts revealed a depressed sensitivity to calcium ions. Gousiekte n-actomyosin also showed a significant depression in the rate of superprecipitation with a concomitant increase in the duration of the clearing phase. We conclude from these observations that a definite biochemical lesion is induced in the contractile proteins of heart muscle obtained from sheep intoxicated with "gousiektebossie" at the stage of cardiac failure. This condition is characterized by abnormal superprecipitation characteristics and a depressed n-actomyosin:ATP-ase activity, showing a reduced sensitivity to the activating effect of calcium ions.
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PMID:A study on the function of some subcellular systems of the sheep myocardium during gousiekte. II. The contractile protein system. 718 38

We report a 46-year-old man with bacterial endocarditis and cardiac failure, who developed status epileptics. The patient was apparently well until July of 1991 when there was a gradual onset of fever and general fatigue. He was hospitalized to the cardiology service of our hospital where diagnosis of bacterial endocarditis and aortic insufficiency was made. On October 9, 1991, he suddenly developed cardiogenic shock, and emergency replacement of the aortic valve was made; at the operation, the main trunk of the left coronary artery showed embolic occlusion, and the myocardial movement was markedly diminished; serum creatine kinase was 3.150 IU/l. His cardiac failure did not resolve, and renal failure developed in December 1991, for which peritoneal dialysis was necessary. On February 2, 1992, he suddenly developed a clonic seizure which started from his face with a transient post-ictal left hemiparesis; a cranial CT scan was unremarkable. He was treated with phenytoin and glycerol, however, he developed status epileptics on February 3; he developed cardiac arrest after the injection of phenytoin 750 mg. He was resuscitated, however, his status did not resolve. Neurological consultation was asked on February 4. On physical examination, his blood pressure was 80/40 mmHg heart rate 77/min and regular, and body temperature 39.1 degrees C. The palpebral conjunctiva were slightly anemic, however, the bulbar conjunctiva were not icteric. No cervical adenopathy was noted. Glade II systolic murmur was heard in the apex; the lungs were clear. The abdomen was flat and soft without organomegaly. No edema was present in the legs. On neurologic examination, he was comatose without response to painful stimuli. He repeatedly had convulsion lasting for 30 seconds every 2 to 3 minutes; his convulsions started with the conjugate deviation of the eyes to the left followed by turning of the head toward left, and then clonic convulsions started in this left upper limb extending to other extremities. The optic fundi were unable to visualize because of corneal clouding; light reflex was sluggish on the right side; no oculocephalic response was elicited; corneal reflex was also lost bilaterally. Extremities were hypotonic, and no automatic movement was seen. The triceps brachii reflex was diminished, but all the other deep reflexes were lost; no plantar response was elicited. Meningeal sign was absent. He was treated with intravenous diazepam; the interval of convulsions prolonged, however, blood pressure dropped to 40 to 40 mmHg. On February 4, intravenous thiopental anesthesia was instituted, and assisted respiration was started.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A 46-year-old man with cardiac failure and statues epileptics]. 794 26

Freeze tolerance in the wood frog, Rana sylvatica, is promoted by multiple, integrated physiological responses to ice forming within body tissues. By analyzing the freezing responses of the sympatric, but freeze intolerant, leopard frog (R. pipiens), we sought clues to the evolution of anuran freeze tolerance. Physiological responses critical to R. sylvatica's freeze tolerance, such as the synthesis and distribution of the cryoprotectant glucose, protective dehydration of organs, and deferred cardiac failure, were present, but comparatively less pronounced, in R. pipiens. Both species were innately tolerant of hyperglycemia. Glucose supplements did not enhance the freezing viability of R. pipiens, although in vitro tests of cryoprotectant efficacy revealed that glucose and glycerol provided comparable protection to erythrocytes of both species. We conclude that the evolution of freeze tolerance in R. sylvatica is not only promoted by its desiccation tolerance and the fortuitous biophysical consequences of freezing (e.g., exothermic induction of cardioacceleration and moderation of cooling rate) but also involves a progressive enhancement of fundamental physiological stress responses.
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PMID:Physiological responses of freeze-tolerant and -intolerant frogs: clues to evolution of anuran freeze tolerance. 823 38

To determine if exercise intolerance and fatigue in chronic heart failure could be exacerbated by an abnormal metabolic response to exercise, we studied 12 patients with stable chronic heart failure and 12 normal volunteers during symptom-limited maximal treadmill exercise. Peak VO2 was 17.2 (15.1-19.2) ml.kg-1 x min-1 in patients and 29.9 (26.3-33.5) in controls (mean and 95% confidence intervals; P < 0.0001, t-test). Overall, levels in peripheral venous blood of glucose, glycerol and free fatty acids were greater in patients, although the differences became less marked with increasing exercise intensity. Noradrenaline was elevated in patients at rest, but the peak exercise response was similar to controls. Responses of adrenaline, insulin and glucagon were similar in both groups. We conclude that depletion of the levels of circulating substrates is not contributory to exercise intolerance and fatigue in chronic heart failure. Greater levels of glycerol and free fatty acids may be mediated by excess sympathetic nervous system activity, reflected in elevated noradrenaline levels.
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PMID:Metabolic responses to graded exercise in chronic heart failure. 829 29


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