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)

Long chain fatty acyl-CoA esters are potent in vitro and in vivo inhibitors of adenine nucleotide translocation in heart mitochondria. Within a short time following production of myocardial ischemia, the dog heart exhibits an increased concentration of long chain acyl-CoA esters associated with a decrease in adenine nucleotide translocase activity. In contrast to liver, the tricarboxylate carrier system for citrate and phosphoenolpyruvate is rather low in heart mitochondria. Phosphoenolpyruvate-stimulated calcium egress from heart mitochondria may, therefore, result from transport of this anion on the adenine nucleotide translocase. During myocardial ischemia effective modulation of these metabolite trasnport systems are disrupted by accumulation of long chain acyl-CoA esters which leads to a decrease in the overall energy charge of the cell.
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PMID:Control of energy production in myocardial ischemia. 126 92

The course administration of a carnitine biosynthesis inhibitor mildronate (100 mg/kg, orally, for 10 and 30 days) was shown to increase the rat blood serum concentration of free fatty acids. By the 30th day of the treatment no changes in the rat myocardium contents of free fatty acids, triglycerides and cholesterol were found that along with the prevention of the accumulation of long chain metabolites of fatty acids in the heart under conditions of adrenergic actions indicated the pathogenetically right approach to the treatment of ischemic heart disease with mildronate.
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PMID:[The effect of the carnitine biosynthesis inhibitor mildronate on the lipid metabolic indices of rats]. 188 99

For a charged and an uncharged long chain spin probe the partition between the aqueous phase and the lipoproteins LDL, HDL2 and HDL3 was measured by use of ESR spectroscopy. The partition coefficients were compared for lipoproteins from normal donors and lipoproteins from patients with ischemic heart disease. The partition coefficients of the uncharged spin probe are not different. However, the charged spin probe has a significantly different partition for LDL and HDL3. This difference results from changes in the surface charge. Patients with ischemic heart disease have LDL which is more electropositively charged and HDL3 is more electronegatively charged compared to the corresponding lipoproteins of normal subjects. The surface charge of HDL2 is not changed. The results are discussed in the light of current concepts of the pathogenesis of atherosclerosis.
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PMID:Alterations of surface charges of plasma lipoproteins in ischemic heart disease. 303 40

Fatty acids are known to increase the severity of injury during acute myocardial ischemia. In this study, we determined the effects of a carnitine palmitoyltransferase I inhibitor, ethyl 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (Etomoxir) on reperfusion recovery of fatty acid perfused hearts. Following a 25-minute period of global ischemia, isolated working hearts reperfused with 1.2 mM palmitate, 11 mM glucose exhibited depressed function compared to hearts perfused with 11 mM glucose alone. A low dose of Etomoxir (10(-9) M) decreased long chain acylcarnitine and long chain acyl-coenzyme A (CoA) levels but did not prevent depressed function. In contrast, a high dose of Etomoxir (10(-6) M) prevented the palmitate-induced depression of function but did not decrease myocardial long chain acylcarnitine or long chain acyl-CoA levels. At this high dose of Etomoxir, oxygen consumption per unit work was decreased during reperfusion recovery, and ATP and creatine-phosphate levels were significantly higher after reperfusion. In aerobic hearts not subjected to ischemia, Etomoxir (10(-6) M) increased glucose oxidation both in the presence and absence of palmitate, while 10(-9) M Etomoxir had no effect. In these aerobic hearts, only the low dose of Etomoxir decreased long chain acylcarnitine and long chain acyl-CoA levels. These data demonstrate that Etomoxir (10(-6) M) increases functional recovery of fatty acid perfused ischemic hearts. This protection is unrelated to changes in levels of long chain acylcarnitines but may be due to increased glucose use by the reperfused heart, resulting in decreased oxygen consumption per unit work.
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PMID:Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. 319 71

Though the efficacies of procainamide and disopyramide in treating arrhythmias are well established, their precise mechanisms of antiarrhythmic action remain unclear. Arrhythmias which occur during acute myocardial ischemia can be explained partly on a metabolic basis. The accumulation of intermediates subsequent to impaired beta-oxidation of free fatty acids has been suggested as a cause of serious arrhythmias. The purpose of this study was to investigate changes in free carnitine, long chain acyl carnitine and long chain acyl CoA concentrations in the ischemic canine heart following the administration of procainamide and disopyramide. The coronary artery was occluded for 40 min and myocardial samples were prepared from both nonischemic and ischemic areas. Procainamide and disopyramide prevented the accumulation of long chain acyl carnitine and long chain acyl CoA in the ischemic myocardium. The results showed that procainamide and disopyramide had beneficial effects on fatty acid metabolism. It was suggested that one of the antiarrhythmic mechanisms of these drugs might be the prevention of the accumulation of fatty acyl derivatives in the ischemic myocardium.
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PMID:Effects of procainamide and disopyramide on long chain acyl carnitine and long chain acyl CoA concentrations in the ischemic heart. 324 36

The accumulation of intermediates subsequent to impaired beta-oxidation of free fatty acid (FFA) has been suggested as a cause of cellular damage in ischemic myocardium. We investigated the effects of propranolol and diltiazem on carnitine metabolism in ischemic myocardium. Propranolol (0.2 mg/kg/min, i.v.) and diltiazem (0.1 mg/kg/min, i.v.) were administered for 5 min, the administration started 10 min before coronary occlusion. ECGs were continuously recorded throughout the experiment. Myocardial samples were prepared from both the non-ischemic and ischemic areas 40 min after coronary ligation. Adenosine triphosphate (ATP), free carnitine, long chain acyl carnitine and long chain acyl CoA were assayed. Propranolol reduced the decrease of ATP and the accumulation of long chain acyl CoA, induced by myocardial ischemia. Diltiazem reduced the decrease of ATP and free carnitine, and the accumulation of long chain acyl carnitine in the ischemic area. Propranolol and diltiazem significantly reduced the grade of ventricular arrhythmia. These results suggest that the protective mechanisms of propranolol and diltiazem on myocardium are based, at least in part, on their beneficial effects upon myocardial carnitine metabolism.
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PMID:Effects of propranolol and diltiazem on carnitine derivatives and acyl CoA in ischemic myocardium. 409 37

Calcium entry into cardiac cells is believed to be controlled by transmembrane-voltage dependent, protein regulated "channels." The sarcoplasmic reticulum participates in the regulation of cytosolic calcium by ATP dependent Ca2+ sequestration during diastole, and by action potential stimulated calcium release. Massive calcium overloading occurs during reperfusion following myocardial ischemia. Calcium overloading activates phospholipases, which may activate another mechanism involved in lethal cellular injury, that is, the accumulation of long chain fatty acids and their derivatives. These compounds are soluble amphiphiles, and once liberated, they may insert into biological membranes and change membrane composition, physiology, and response to ions and drugs. Sarcoplasmic reticulum vesicles were used as an in vitro model to study the effects of palmitic acid, oleic acid, and palmitylcarnitine on the ability of this membrane system to sequester calcium within the vesicles. In the absence of phosphate, palmitic acid enhanced the ability of the vesicles to sequester calcium. Oleic acid and palmitylcarnitine inhibited calcium sequestration. In the presence of phosphate palmitic acid also inhibited the sequestration of calcium by sarcoplasmic reticulum, although not as severely as oleic acid and palmitylcarnitine. These results suggest that the disturbances in cellular calcium homeostasis following ischemia may be due, in part, to the incorporation of accumulated long chain fatty acids into membranes.
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PMID:The possible role of endogenous amphiphiles in the membrane abnormalities of ischemic and reperfused myocardium. 668 Jun 16

In order to evaluate the protective effects of L-carnitine on ischemic myocardium, its effects on tissue levels of free fatty acid (FFA), acyl CoA, acyl carnitine, and adenosine triphosphate (ATP) were studied in ischemic dog hearts. Myocardial ischemia was induced by the ligation of left anterior descending coronary artery for 15 min. L-Carnitine (100 mg/kg) was administered intravenously prior to coronary ligation. In ischemic myocardium, tissue levels of free carnitine and ATP decreased, whereas long-chain acyl carnitine, long-chain acyl CoA, and FFA increased. Pretreatment of L-carnitine prevented the decrease in free carnitine and ATP and the increase in long-chain acyl carnitine and long-chain acyl CoA. A positive correlation was observed between ATP and free carnitine. On the other hand, a negative correlation was observed not only between ATP and the ratio of long-chain acyl CoA to free carnitine but also between ATP and the ratio of long-chain acyl carnitine to free carnitine. These results suggest that L-carnitine has protective effects on ischemic myocardium, probably by preventing the accumulation of long-chain acyl carnitine and long chain acyl CoA.
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PMID:Effects of L-carnitine on tissue levels of free fatty acid, acyl CoA, and acylcarnitine in ischemic heart. 685 80

The effects of L-carnitine on ventricular arrhythmias were evaluated in dogs with acute myocardial ischemia and a supplement of excess free fatty acids (FFA). Acute myocardial ischemia was induced by ligation of left anterior descending coronary artery. After 80 minutes of coronary occlusion, high plasma FFA was induced by intravenous injection of heparin 200 mu/kg and Intralipid 5 ml/kg as a bolus. After additional 60 minutes, beating hearts were removed from animals and tissue levels of free carnitine, short and long chain acyl carnitine, FFA and adenosine triphosphate (ATP) were determined. L-carnitine 100 mg/kg was administered intravenously 5 minutes before coronary artery ligation. Electrocardiograms were recorded continuously by a Holter electrocardiographic recorder during the experiment and ventricular arrhythmias were quantified by an arbitrary scoring system. In ischemic and excess FFA supplemented myocardium, free carnitine and ATP decreased, whereas long chain acyl carnitine and FFA increased. And these metabolic changes tended to be reduced by L-carnitine. Pretreatment of L-carnitine also reduced the grade of ventricular arrhythmias induced both by acute myocardial ischemia and by supplemented of excess FFA. These results suggest that the administration of L-carnitine may be beneficial to prevent serious arrhythmias in ischemic heart disease, presumably by restoring the imparied FFA oxidation.
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PMID:Effects of L-carnitine on ventricular arrhythmias in dogs with acute myocardial ischemia and a supplement of excess free fatty acids. 723 May 9

Long-chain acylcarnitines accumulate during myocardial ischemia and contribute to membrane dysfunction in ischemic zones. On the basis of the 3-fold selectivity for saturated fatty acid accumulation during myocardial ischemia, it was implicitly assumed that saturated long chain acylcarnitine molecular species predominantly accumulated in ischemic myocardium. By exploiting the analytical power of electrospray ionization mass spectroscopy, we now report that unsaturated acylcarnitines are the predominant molecular species of acylcarnitine which accumulate during myocardial ischemia (rank order: octadecadienoyl carnitine > octadecanoyl carnitine > hexadecanoyl carnitine > octadecanoyl carnitine). The aliphatic chain distribution of myocardial acylcarnitine molecular species identified by electrospray ionization mass spectroscopy was independently substantiated by sequential HPLC purification and capillary gas chromatography. Detailed analysis of the individual molecular species of long-chain acylcarnitine demonstrated that fatty acyl chain elongation was prominent in ischemic myocardium (e.g., following 20 min of ischemia, greater than 15% of the accumulated acylcarnitines consisted of 20-carbon unsaturated molecular species). Chain-elongated lipids were essentially confined to the long chain acylcarnitine pool since [9,10-3H]octadec-9'-enoic acid was converted to [3H]eicosenoyl carnitine (12% of the radiolabeled acylcarnitine pool) in ischemic hearts without substantive amounts of [3H]eicosenoyl residues in the fatty acid, triglyceride, and phospholipid pools. Collectively, these results demonstrate the preponderance of unsaturated acylcarnitines in ischemic myocardium and document the metabolic compartmentation of downstream products of fatty acyl chain elongation in the acylcarnitine pool during ischemia.
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PMID:Accumulation of unsaturated acylcarnitine molecular species during acute myocardial ischemia: metabolic compartmentalization of products of fatty acyl chain elongation in the acylcarnitine pool. 867 92


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