Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although L-carnitine is not considered as an essential nutrient, endogenous synthesis may fail to ensure adequate L-carnitine levels in neonates, especially those born prematurely. Free L-carnitine is found in many foods, mainly those from animal sources. Absorption of free L-carnitine is virtually complete. Lysine and methionine are necessary ingredients for the biosynthesis of L-carnitine. All tissues in the body can produce deoxy-carnitine but, in humans, the enzyme that enables hydroxylation of deoxy-carnitine to carnitine is found only in the liver, brain and kidneys. Complex exchanges of carnitine and its precursors occur between tissues. Muscles take up carnitine from the bloodstream and contain most of the body carnitine stores. L-carnitine and L-carnitine esters are eliminated mainly through the kidneys, which may play a central role in the homeostasis of this compound. Thyroid hormones adrenocorticotrophin (ACTH), and diet all influence urinary excretion of L-carnitine. Free L-carnitine can be assayed in plasma and urine and is occasionally measured in muscle biopsy specimens. Plasma L-carnitine levels may not accurately reflect L-carnitine body stores. L-carnitine ensures transfer of fatty acids to the mitochondria where they undergo oxidation. This process is associated with production of short-chain acylcarnitine which exit from the mitochondria or peroxisomes. L-carnitine ensures regeneration of coenzyme A and is thus involved in energy metabolism. L-carnitine also ensures elimination of xenobiotic substances. Carnitine deficiencies are common. Currently, these deficiencies are classified into two groups. In deficiencies with myopathy, only the muscles are deficient in L-carnitine, perhaps as a result of a primary anomaly of the L-carnitine transport system in muscles. In systemic deficiencies, L-carnitine levels are low in the plasma and in all body tissues. Systemic L-carnitine deficiencies are usually the result of a variety of disease states including deficient intake in premature infants or long-term parenteral nutrition; renal failure; organic acidemias; and Reye's syndrome. Modifications in L-carnitine metabolism have also been reported in patients with diabetes mellitus, malignancies, myocardial ischemia, and alcohol abuse. A large number of supplementation trials have been carried out.
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PMID:[L-carnitine: metabolism, functions and value in pathology]. 129 65

Carnitine, certain of its derivatives, and the amino acid metabolite, taurine, when administered independently in prior studies have been shown to improve cardiac mechanic and/or metabolism. The purpose of these studies is to test a new compound, propionylcarnitine taurine (PCT), which potentially combines these actions, in a therapeutic trial to preserve function in a setting of myocardial ischemia. In the main protocol, PCT was administered (0.71 mg/kg/min I.V.) to eight extracorporeally perfused, intact, working swine hearts over a 70 min perfusion trial and compared with seven similarly prepared placebo hearts. Left anterior descending (LAD) flows were held at aerobic levels (6.3 +/- 0.3 ml/min/g dry) for 40 min and then reduced acutely by 50% for 30 min. Serum fatty acids (FA) in both groups were augmented to 1.27 +/- 0.5 mumol/ml. Contractility (measured regionally from shortening rates of ultrasonic crystals placed in the LAD circulation); myocardial oxygen consumption (MVO2); and FA oxidation (measured from 14CO2 production rates from labeled palmitate infused into the LAD perfusate) were obtained serially throughout the perfusion trials. Regional contractility was significantly increased in PCT-treated hearts as compared with placebo hearts both during normal and ischemic flows. Treatment appeared to deplete free carnitine stores in both aerobic and ischemic myocardium but failed to modify acyl CoA levels. In seven additional animals PCT was shown to independently stimulate fatty acid oxidation (about 39 delta % increase) at aerobic flows. Lastly in nine separate animals (4 placebo; 5 treatment) prepared and studied identically to those of the main protocol, taurine alone (0.2 mg/kg/min infused IV for 70 min) was without influence in reproducing mechanical benefits. Thus, PCT favorably enhances regional contractility in conditions of myocardial ischemia, presumably by the positive inotropic effects of the propionylcarnitine constituent of the compound.
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PMID:The effects of propionylcarnitine taurine on cardiac performance in aerobic and ischemic myocardium. 336 80

Infusions of DL-carnitine are reported to improve the tolerance to atrial pacing of patients with angina pectoris. In the present study, six patients with angina of effort and triple vessel disease received two placebo and two carnitine infusions administered in a double-blind randomized fashion. Carnitine did not affect either the double product (heart rate X systolic blood pressure) at maximal pacing (ST depression: 2.3 +/- 0.2 mm, +/- SEM) or the tolerated pacing time. Intravenous carnitine, in the dose given, is of no therapeutic benefit in myocardial ischemia precipitated by tachycardia. It could be effective when free fatty acids are elevated as during catecholamine stimulation.
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PMID:Intravenous dl-carnitine fails to increase the double-product during atrial pacing in patients with effort angina. A double-blind randomized study. 666 14

Myocardial ischaemia may be defined as a deficiency in cardiac energy supply relative to energy demand. In coronary artery disease (CAD), oxygen supply is limited due to coronary obstruction so energy production is not enough to meet the energy demands for work. Several reports involving about 2500 patients of CAD where carnitine was administered for upto 1 year indicate some beneficial effects. There is reduction in ischaemia showing reduced ST-segment depression and angina, greater effort tolerance and decreased need of cardiac drugs. Carnitine can cause overall improvement in cardiac performance in patients with CAD as well as in cardiomyopathy. More studies are necessary to demonstrate where carnitine can scavenge free radicals apart from its beneficial effect on fatty acid metabolism. Side effects of carnitine are mild nausea and vomiting and dose upto 2 g/day in 3 divided doses may not have any side effects. Intravenous L-carnitine acts rapidly and has no side effects.
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PMID:L-carnitine administration in coronary artery disease and cardiomyopathy. 1122 53

Carnitine and its derivatives have recently been shown to protect cardiac metabolism and function in ischemic heart disease and other clinical conditions of myocardial ischemia. Potential mechanisms of this effect include an increase in glucose metabolism, a reduction of toxic effects of long-chain acyl-CoA and acyl-carnitine in myocytes, an increase in coronary blood flow and anti-arrhythmic effect. It has also been shown that propionyl-L-carnitine which penetrates faster than carnitine into myocytes is effective in inhibiting production of free radicals. Beneficial effects of carnitine supplementation have been demonstrated under a variety of clinical conditions such as acute cardiac ischemia, during extracorporeal circulation, in carnitine-dependent cardiomyopathy as well as in patients with chronic circulatory failure and in cardiogenic shock. However, further studies are required before carnitine administration could be recommended as a routine procedure in ischemic heart disease or before cardiopulmonary bypass.
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PMID:Influence of L-carnitine and its derivatives on myocardial metabolism and function in ischemic heart disease and during cardiopulmonary bypass. 1139 44

Carnitine is an essential cofactor for fatty acid (FA) metabolism, the predominant source of ATP in the normal aerobic heart. During myocardial ischemia, FA metabolism is impaired and tissue carnitine levels are depleted. Since the heart cannot synthesize carnitine, plasma carnitine could play an important role in maintaining myocardial carnitine levels during reperfusion. The purpose of this study was to determine the incidence of abnormal plasma carnitine concentrations in open heart surgery. Blood samples were obtained from eleven patients before, immediately after, and two hours after cardiopulmonary bypass (CPB). Total and free carnitine levels were significantly reduced immediately after CPB (p<0.01) and remained depressed until two hours after CPB (p<0.01 vs. pre CPB), while acyl carnitine levels were unchanged over the course of this study. These depressed free carnitine levels might affect cardiac metabolism in the heart after open heart surgery. Carnitine supplement might be a useful adjunct in the therapy after open heart surgery.
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PMID:Plasma carnitine concentrations in patients undergoing open heart surgery. 1500 94