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

Carnitine concentration was measured in plasma, muscle, and dialysate before and after haemodialysis in patients with renal failure and in plasma and muscle of healthy controls. In eight of the nine patients carnitine concentration in muscle after haemodialysis was only 10% of the concentration in controls. Plasma-carnitine varied in patients before dialysis and in all of them was reduced by dialysis. The loss of carnitine into the dialysate (190--2100 mumol/treatment) greatly exceeded the normal loss in urine for most of patients, and was only partly compensated for. In some patients normal or high plasma-carnitine and low concentrations in muscle indicated that the carnitine-concentrating mechanisms in the muscle cell had failed. The reduction in carnitine will interfere seriously with normal cellular functions and this may help to explain the clinical syndrome of cardiomyopathy and cardiac failure which has been observed in some patients treated for a long time with intermittent haemodialysis.
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PMID:Carnitine deficiency induced during intermittent haemodialysis for renal failure. 8 56

Carnitine, once known as vitamin Bt, is intrinsic to human tissue and is biochemically established as being acylated with fatty acids by Acyl-CoA to give Acyl-carnitines which then are transported to the inner mitochondrial membrane by a translocase. Carnitine is of increasing clinical interest and importance, and endomyocardial deficiencies of carnitine have been reported for patients in heart failure. Consequently, a reproducible and accurate analysis of human tissue specimens for levels of free carnitine and Acyl-carnitine to guide and to support continuing clinical studies of disease states is needed. We have devised an analytical method which utilizes 5,5'-dithiobis-2-nitro-benzoate and demonstrated recovery, reproducibility and precision. Hydrolysis of a specimen at 90 degrees C for 15 min, and control of pH below 6.0 are critical steps. The mean levels of free carnitine and total carnitine in 17 ordinary subjects were 50.6 +/- 9.7 nmol./ml and 62.6 +/- 11.7 nmol./ml. respectively.
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PMID:Improved methodology to assay carnitine and levels of free and total carnitine in human plasma. 203 34

Severe tissue carnitine deficiency impairs fatty acid oxidation. In explanted hearts from patients with end stage heart failure a 57% carnitine decrease was found in comparison with healthy donor hearts (p less than 0.05). The reduction of myocardial carnitine levels affected all areas of the explanted hearts to a comparable extent. Carnitine decreases in patients with dilated cardiomyopathy or coronary artery disease were similar. Endomyocardial biopsies from patients with less severe heart failure due to cardiomyopathy (n = 28) or other myocardial diseases (n = 8) showed a 42% decrease of total myocardial carnitine (in nmol/mg non-collagen protein) in comparison with biopsies from patients with normal cardiac function (controls) (heart failure: 5.7, confidence interval 4.2-7.0; controls 9.3, confidence interval 7.6-12.0, p less than 0.005). Free myocardial carnitine in heart failure was also different from controls (heart failure: 4.2, confidence interval 3.7-5.3; controls 10.3, confidence interval 7.5-12.2, p less than 0.001). The decrease of free and total myocardial carnitine was comparable in dilated cardiomyopathy and heart failure due to other diseases. Alterations in myocardial carnitine content represent therefore non-specific biochemical markers in heart failure with yet unknown consequences for myocardial function.
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PMID:Metabolic alterations in end-stage and less severe heart failure--myocardial carnitine decrease. 229 80

Biochemical analyses from endomyocardial biopsies indicate that cardiac energy metabolism is altered in patients with end-stage cardiac failure. Myocardial energy production is predominantly based on fatty acid oxidation. Carnitine, a naturally occurring compound, plays an essential role in fatty acid oxidation by carrying long-chain fatty acids into the mitochondrial matrix where they undergo beta-oxidation. In experimental animals, myocardial carnitine deficiency may cause cardiomyopathies which are reversible with carnitine substitution. Rare human diseases, as systemic carnitine deficiency, are associated with impaired cardiac function. We therefore investigated carnitine metabolism in patients with cardiac failure. Plasma and myocardial carnitine levels were measured in 55 patients undergoing cardiac transplantation because of end-stage cardiac failure based on dilated cardiomyopathy (DC, n = 30) or coronary artery disease (CAD, n = 22). Elevated plasma carnitine levels (controls: 49 +/- 12 microM; DC: 82 +/- 38 microM; p less than 0.001, CAD: 86.9 +/- 21.6 microM; p less than 0.05) were found in both patient groups (Fig. 1). Plasma carnitine did not correlate with creatinine (Fig. 2). Compared to controls, myocardial carnitine levels were significantly reduced: DC: 5.9 +/- 1.45 nmol/mg NCP; CAD: 5.84 +/- 1.84 nmol/mg NCP; controls: 15.6 +/- 5.4 nmol/mg NCP (Fig. 3). No correlation between myocardial and plasma levels was found (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Carnitine metabolism--changes in the end stage of dilated cardiomyopathy and ischemic heart muscle disease]. 332 28

Carnitine and acylcarnitines were measured in plasma and tissues of control turkeys, turkeys with an inbred spontaneous cardiomyopathy, and turkeys with furazolidone-induced cardiomyopathy. Heart failure was evident in both types of cardiomyopathy from decreased systemic blood pressure and cardiac dilatation compared to controls. Plasma free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine were significantly elevated by 76 to 614% (p less than 0.01) in the two cardiomyopathy models compared to control. The highest carnitine levels were found in the most hypotensive turkeys. Liver free carnitine and short-chain acylcarnitine levels were also elevated by 45 to 537% (p less than 0.05) in both types of cardiomyopathy. Free carnitine was elevated by 126% in left ventricle and by 54% in skeletal muscle of the furazolidone-treated turkeys (p less than 0.05). We speculate that hepatic synthesis of carnitine may be increased in response to hypotension and progressive cardiac dysfunction in cardiomyopathic turkeys. Such an increase may be useful to promote beta-oxidation of fatty acids as a cardiac energy source.
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PMID:Carnitine alterations in spontaneous and drug-induced turkey congestive cardiomyopathy. 400 Jul 66

Carnitine, an important cofactor in the transport of fatty acids to the interior of cell mitochondria, is depleted in myocardial tissue of guinea pigs submitted to diphtheric toxin administration. Mortality rates were reduced in these animals by supplying exogenous amounts of carnitine. The accumulation of fatty acids in the cytoplasm of human heart cells reported in cases of diphtheria suggests that carnitine might possibly be depleted in human myocardium as well. For the purpose of studying the effect of carnitine administration, 132 diphtheric patients were randomly divided into two groups, one of them (carnitine-treated group, n = 73) receiving DL-carnitine, 100 mg/kg/day during 4 days after admission, in addition to routine treatment, which was prescribed for this and the control group (n = 59). The presence of myocardial damage was evaluated by clinical, electrocardiographic, radiological, and enzymatic criteria. Carnitine administration resulted in decreased incidence of heart failure (P = 0.0475), of pacemaker implants (P = 0.0256), and of lethality indexes due to myocarditis (P = 0.013). We suggest that carnitine can play an important role in the treatment of diphtheric patients.
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PMID:The protective effect of carnitine in human diphtheric myocarditis. 648 4

The clinical significance of nutritional carnitine deficiency remains controversial. To investigate this condition under controlled conditions, an animal model was developed using the parenterally alimented, carnitine-deprived newborn piglet. Forty-five piglets received total parenteral nutrition for 2-3 wk that was either carnitine-free or supplemented with 100-400 mg/L L-carnitine. Blood and a muscle biopsy were taken at the initial surgery. Carnitine balance studies were performed at 11-14 d of age. Blood, liver, heart, and skeletal muscle were taken at sacrifice for analysis of carnitine, electron microscopy, and oxidation studies. Carnitine-deprived piglets were in negative carnitine balance and had lower blood, urine, and tissue levels of carnitine than carnitine-supplemented animals. There was a positive correlation between excretion and plasma concentrations of free carnitine with an apparent renal threshold between 15 and 35 micromol/L. Plasma levels were correlated with liver and heart, but not muscle, concentrations of total acid-soluble carnitine. Carnitine-deprived piglets had evidence of lipid deposition in liver and skeletal muscle and tended to have a higher incidence of muscle weakness and cardiac failure. Basal rates of oxidation of [14C]palmitate to 14CO2 and 14C-acid-soluble products were lower in liver homogenates from carnitine-deprived piglets than in those from carnitine-supplemented animals and increased in a dose-dependent fashion with the addition of L-carnitine (0, 50, and 500 micromol/L) in vitro. In summary, carnitine deprivation in the neonatal piglet resulted in low carnitine status and morphologic/functional disturbances compatible with carnitine deficiency. The described animal model appears to be suitable for the investigation of neonatal nutritional carnitine deficiency.
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PMID:Neonatal nutritional carnitine deficiency: a piglet model. 921 46

Carnitine transporter defect is characterized by severely reduced transport of carnitine into skeletal muscle, fibroblasts, and renal tubules. All children with dilated cardiomyopathy or hypoglycemia and coma should be evaluated for this transporter defect because it is readily amenable to therapy that results in prolonged prevention of cardiac failure. This article details the cases of 3 children who have carnitine transporter defect, 2 of whom had severe dilated cardiomyopathy. Plasma and skeletal muscle carnitine levels were extremely low and both children were treated with oral L-carnitine, resulting in resolution of severe cardiomyopathy and prevention of recurrence or cardiac enlargement for more than 5 years. The third child had hypoglycemia and coma as presenting findings of the transporter defect and had mild left ventricular hypertrophy but no cardiac failure. The prognosis for long-term survival in pediatric dilated cardiomyopathy is poor. Children with carnitine transporter defect can have a different outcome if their underlying condition is detected early and treated medically.
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PMID:Familial carnitine transporter defect: A treatable cause of cardiomyopathy in children. 1065 Mar 22

Left ventricular dilatation after acute myocardial infarction (MI) is a powerful predictor of progressive functional deterioration, culminating in heart failure and death. The most important determinants of post-MI left ventricular remodeling are the size of the infarct, the degree of residual stenosis in the infarct-related artery, and the viability of the infarct zone. In addition to reperfusion therapy and angiotensin-converting enzyme inhibition, metabolic intervention with L-carnitine may represent a therapeutic approach for preventing left ventricular dilatation and preserving cardiac function. Ongoing studies with early metabolic intervention with carnitine in the acute phase of infarction may prove successful in protecting the microcirculation against ischemic damage and enhancing its ability to respond to blood flow resumption. The results of the multicenter, randomized, double-blind Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial suggest that the early and long-term administration of L-carnitine attenuates progressive left ventricular dilatation after acute anterior MI. Results show significant, consistent reductions in end-diastolic volume and end-systolic volume in patients who received L-carnitine compared with placebo. The ongoing CEDIM-2 trial (projected 4000 patients with acute MI) will assess the efficacy of L-carnitine in reducing the combined incidence of death and heart failure at 6 months. In addition to standard reperfusion therapy and angiotensin-converting enzyme inhibition, metabolic intervention with L-carnitine may be a therapeutic approach for preventing left ventricular dilatation and preserving cardiac function by limiting infarct size, decreasing residual stenosis in the infarct-related artery, and increasing viability of the infarct zone.
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PMID:Myocardial infarction and left ventricular remodeling: results of the CEDIM trial. Carnitine Ecocardiografia Digitalizzata Infarto Miocardico. 1065 Mar 26

Heart failure (HF) is associated with weight loss, and cachexia is a well-recognized complication. Patients have an increased risk of osteoporosis and lose muscle bulk early in the course of the disease. Basal metabolic rate is increased in HF, but general malnutrition may play a part in the development of cachexia, particularly in an elderly population. There is evidence for a possible role for micronutrient deficiency in HF. Selective deficiency of selenium, calcium and thiamine can directly lead to the HF syndrome. Other nutrients, particularly vitamins C and E and beta-carotene, are antioxidants and may have a protective effect on the vasculature. Vitamins B6, B12 and folate all tend to reduce levels of homocysteine, which is associated with increased oxidative stress. Carnitine, co-enzyme Q10 and creatine supplementation have resulted in improved exercise capacity in patients with HF in some studies. In this article, we review the relation between micronutrients and HF. Chronic HF is characterized by high mortality and morbidity, and research effort has centered on pharmacological management, with the successful introduction of angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists into routine practice. There is sufficient evidence to support a large-scale trial of dietary micronutrient supplementation in HF.
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PMID:Chronic heart failure and micronutrients. 1140 Nov 9


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