Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiotoxicity limits the use of anthracyclines which are potent anticancer agents. In the isolated rat heart, we investigated the mechanism of acute anthracycline cardiotoxicity and compared a new anthracycline, carminomycin, with daunomycin which is in established use. Daunomycin 1.75 X 10(-5) M produced a fall in cardiac output (36 +/- 2 versus 58 +/- 1 ml/min; p less than 0.01), left ventricular power production (9 +/- 0.7 versus 16 +/- 0.3 mJ/sec/g; p less than 0.01), and efficiency of heart work (3.3 +/- 0.2 versus 6.3 +/- 0.2 mJ/sec/ml O2; p less than 0.01; mean +/- S.E. 40 min after daunomycin). Carminomycin (1.75 X 10(-5) M) produced a greater fall in cardiac output than equimolar daunomycin (26 +/- 2 versus 36 +/- 2 ml/min; p less than 0.01). Daunomycin did not reduce coronary flow rate, heart rate, or oxygen consumption. From the preceding data, we inferred that, since afterload and preload were constant in this model, heart failure was due to a depressed inotropic state. Procedures that increased cytosolic calcium relieved heart failure namely, pretreatment with digoxin (62.4 micrograms), isoproterenol (10(-6) M), and increased perfusate Ca2+ (5 mM versus 2.5 mM) all prevented carminomycin-induced fall in cardiac output (41 +/- 1, 47 +/- 5, and 52 +/- 1, respectively, versus 26 +/- 2 ml/min; p less than 0.01). Acute anthracycline contractile failure was also associated with a fall in high-energy phosphate compounds which could also have contributed to the decreased inotropic state. We conclude that carminomycin is more cardiotoxic than daunomycin in equimolar concentrations and that a lowered cytosolic calcium and decreased energy stores might cause the contractile failure. The cytosolic calcium and high-energy phosphate compounds were lowered by separate mechanisms.
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PMID:Mechanism of acute anthracycline cardiotoxicity in isolated rat hearts: carminomycin versus daunomycin. 670 50

Over 97% of all uroliths in males less than a year of age and in females are phosphate, excluding males with portosystemic shunts and male Dalmatians . Uroliths in male Dalmatians usually are composed of urate. Uroliths associated with Staphylococcus aureus urinary tract infection are phosphate. About 60% of uroliths in adult male Basset Hounds , Bulldogs , Chihuahuas , Irish Terriers and Yorkshire Terriers are cystine. In males of other breeds, as high as 60% of uroliths are phosphate. Feeding a calculolytic diet (s/d: Hill's) results in phosphate urolith dissolution in 2-20 weeks. Long-term feeding of the calculolytic diet is not recommended, nor is use after surgery and in pregnant, lactating or growing dogs and in those with heart failure, edema, ascites or pleural effusions. Uroliths recur in 20-50% of affected dogs without subsequent dietary alteration. Use of a urolith-prevention diet (u/d: Hill's) is recommended if urolithiasis recurs.
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PMID:Canine urolithiasis: diagnosis and treatment. 673 11

1 To evaluate oral disopyramide phosphate in the prophylaxis of dysrhythmias occurring in acute myocardial infarction (MI) patients (presenting within 12 h of symptoms, age 21-70 years), a placebo-controlled, randomized double-blind, in hospital trial was conducted. After prognostic stratification (anterior and non-anterior MI at each of 4 regional hospitals) patients were randomly assigned to receive oral disopyramide phosphate (loading dose 150, 200, or 300 mg followed 6 h later by 100, 150, or 200 mg every 6 h for patients assessed to weigh less than 55, 55-85, or greater than 85 kg, respectively or matching placebo. The primary exclusion criteria were overt heart failure, systolic BP less than 100 mmHg, significant heart block or history of urinary retention. Active drug or placebo was continued for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 premature ventricular contractions (PVCs)/min, R on T PVCs, multifocal PVCs, bigeminal PVCs, ventricular tachycardia or ventricular fibrillation) or (b) onset of exclusion criteria. In addition, plasma drug concentrations were determined and 24 h electrocardiographic tapes were obtained on day 1, and on one of days 4-7 but these results are not presented here. 2 Out of 121 patients entering the trial, 101 had confirmatory ECG and enzyme changes. Of these, 9 of 47 patients receiving disopyramide phosphate required lignocaine compared to 20 of 54 receiving placebo (19% v 37%; P = 0.047). Corresponding numbers for patients discontinuing trial medication for other non-fatal complications of MI were 5 and 3, and for those dying, were 3 (2 infarct extensions and 1 massive infarction), and 0, respectively. Respective numbers discontinuing trial medication for possible drug side effects (viz. urinary retention requiring catheterization) were 6 and 1 (P = 0.031). 3 In circumstances where i.v. therapy is deemed impractical, use of oral disopyramide phosphate given prophylactically in patients with acute MI may reduce the incidence of "warning arrhythmias' by a clinically significant extent.
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PMID:A placebo-controlled study to determine the efficacy of oral disopyramide phosphate for the prophylaxis of ventricular dysrhythmias after acute myocardial infarction. 675 87

The essential and critical role of inorganic phosphate has been known in veterinary medicine and experimental research on animals for decades. However, only recently has the phosphate depletion syndrome found widespread attention by clinicians. Hypophosphatemia is usually observed in the following clinical situations:chronic alcoholism, recovery phase of diabetic ketoacidosis, administration of phosphate-free solutions in parenteral nutrition, severe respiratory alkalosis, and infusion of fructose. Disturbed organ function in hypophosphatemia is the result of a depletion of inorganic phosphate in the cytoplasm of somatic cells. Such phosphate depletion may be due to either of the following mechanisms or a combination of both. (1) Negative external phosphate balance resulting from phosphate loss in urine or feces or (2) translocation of phosphate from the extracellular into the intracellular space with or without concomitant negative external phosphate balance. In principle, phosphate depletion interferes with the function of all somatic cells. In acute phosphate depletion, the clinically most important disturbances are observed in striated muscle (rhabdomyolysis with myoglobinuric acute renal failure), heart muscle (acute heart failure), and hematological systems (hemolysis, disturbed leukocyte and thrombocyte functions). In contrast, in chronic phosphate depletion skeletal abnormalities (osteomalacia) predominate. Organ disturbances are thought to result from diminished synthesis of ATP and other organic phosphate esters and/or from hypoxia secondary to changes in erythrocyte 2,3-DPG.
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PMID:[Phosphate-depletion (author's transl)]. 676 28

Hypophosphatemia is a common laboratory abnormality that occurs in a wide variety of disorders. When severe and prolonged, it may be associated with rhabdomyolysis, brain dysfunction, myocardial failure and certain defects of erythrocyte function and structure. Other disorders ascribed to hypophosphatemia, including platelet dysfunction and thrombocytopenia, liver dysfunction, renal tubular defects, peripheral neuropathy, metabolic acidosis and leukocyte dysfunction are less well documented. In quantitative terms, the most severe phosphate deficiency is seen in patients who consume a phosphate-deficient diet in conjunction with large amounts of phosphate-binding antacids, in persons with severe, chronic alcoholism and in patients with wasting illnesses who are refed with substances containing an inadequate amount of phosphate. When severe hypophosphatemia occurs in such a setting, the clinical effects appear to be much more pronounced. While there have been some advances in our understanding of the pathophysiology of phosphate depletion and hypophosphatemia, much remains to be learned. Treatment of hypophosphatemia is controversial; however, there is little question that it is indicated in alcoholic patients and those with severe phosphate deficiency.
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PMID:Hypophosphatemia. 701 Jul 90

In order to determine the status of the energy production system of the heart during cardiac failure of sheep with gousiekte, observations were made of the heart tissue levels of adenosine triphosphate (ATP), creatine phosphate (CrP), inorganic phosphate, reduced nicotine adenine dinucleotide (NADH) and lactate. Some measurements on oxidative phosphorylation were also made. A significant decrease in ATP and CrP levels coincided with a simultaneous rise in the ATP:CrP ratio and lactate levels in gousiekte hearts. No significant deviations in inorganic phosphate and NADH levels could be demonstrated. These abnormalities were accompanied by a decreased uptake of oxygen by isolated mitochondria of gousiekte hearts. There was a marked increase in the anaerobic state of the hearts of dying gousiekte sheep, while the values of NADH and the ATP:CrP ratio at a presymptomatic stage indicated a possible early derangement in the energy metabolism of sheep fed the toxic material. No hypertrophy could be detected for the failing ventricles of gousiekte sheep after being corrected for a significant amount of oedema found in the heart tissue of these animals. It was concluded that the depressed ATP and CrP levels in the heart tissue of gousiekte sheep during cardiac failure could at least in part, be attributed to a depressed aerobic energy production. It is not possible, however, to state whether this is a primary or a secondary response due to intoxication and also whether it could be seen as a cause or effect of cardiac failure.
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PMID:A study on the function of some subcellular systems of the sheep myocardium during gousiekte. I. The energy production system. 718 37

Two patients abruptly developed congestive heart failure and elevation in serum transaminase levels when given disopyramide phosphate; enzyme abnormalities and hemodynamic status corrected upon withdrawal of the drug. Both patients had underlying ischemic cardiomyopathy. Myocardial infarction, pulmonary embolism, and viral hepatitis were ruled out in both patients. One patient had a liver biopsy documenting central hepatic necrosis with congestion, consistent with hepatic ischemia and not toxic hepatitis. In the other patient, cardiac decompensation and hepatocellular enzyme elevation were reproduced on rechallenge with the drug. Disopyramide should be used with caution in patients with heart failure.
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PMID:Acute cardiac failure and hepatic ischemia induced by disopyramide phosphate. 722 41

A case of metastatic myocardial calcification is reported in a patient with chronic renal failure. The characteristic features are failure to take phosphate-binding antacids on a regular basis, intractable congestive heart failure, atrioventricular block, a calcium phosphate product consistently greater than 60, and sudden irreversible cardia arrest. Arteriovenous fistulae created for haemodialysis appear to be an unlikely cause of cardiac failure.
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PMID:Metastatic myocardial calcification. 724 27

The effects of intravenous disopyramide phosphate on myocardial function were evaluated by non-invasive indices of cardiac performance (systolic time intervals, STI) in 15 patients with atherosclerotic heart disease and different degrees of cardiac failure. Disopyramide (1.5 mg/Kg) was given intravenously over a period of 5 min. This drug induced in patients in I-II classes of NYHA a significant decrease of LVETc, while PEP, ICT, and PEP/LVET ratio rose significantly. STI were affected much more markedly in patients in III-IV classes of NYHA. Particularly affected were contractility indices (PEP, ICT, PEP/LVET), which were reduced significantly more in patients in III-IV classes as compares to patient in I-II classes. In contrast, LVETc, which correlates to stroke volume and cardiac output, was similarly worsened by the drug in the 2 groups of patients. Therefore, this study shows that disopyramide has relevant depressant effects on myocardial performance, simultaneously reducing stroke volume and contractility, and that the effect on contractility is more marked in patients with severe left ventricular impairment.
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PMID:Effects of intravenous disopyramide on myocardial function in patients with different degrees of cardiac failure. 737 60

The effect of a medroxyprogesterone acetate (MPA) plus epirubicin combination versus estramustine phosphate was evaluated in 149 prospectively randomized patients with hormone-resistant prostatic cancer. The estimated probability of being free from progression after 1 year was 17% for the patients treated with estramustine and 29% for the MPA-epirubicin group. There is a significant difference between the two groups regarding risk of progression (p = 0.013). However, no difference in survival was recorded (p > 0.30) with about 60% of the patients dead during the first year in both groups. Progression was highly correlated to sedimentation rate (p < 0.001) and to performance index (p = 0.002). Heart failure occurred in a substantial number of patients in both groups which must be considered before starting therapy.
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PMID:Epirubicin and medroxyprogesterone acetate versus estramustine phosphate in hormone-resistant prostatic cancer: a prospective randomized study. 765 6


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