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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Failure of glycolysis to increase sufficiently to supply optimal levels of energy production in ischemic heart muscle is due in part to the cummulative restrainst of acidosis on rate-limiting enzymes, particularly glyceraldehyde-3-phosphate dehydrogenase. In an effort to modify this inhibition and salvage jeopardized myocardium, treatment with excess levels of pyruvate and tromethamine (Tris), designed to buffer intracellular hydrogen ion accumulations and improve the oxidation-reduction ratio, NAD+/NADH, was tested in 59 swine hearts in two separate preparations of global and regional ischemia. Global ischemia, per se, caused hemodynamic deterioration and shortened survival time (44.3 +/- 3.1 minutes). Myocardial oxygen consumption, fatty acid oxidation, and glucose uptake were all significantly (P less than 0.001) reduced as were estimates of glycolysis and tissue stores of creatine phosphate and ATP (P less than 0.01). Although treatment with Tris alone was inconclusive, administrations of pyruvate (40-50 mM) buffered with Tris (added directly into the coronary perfusate) effected an improvement in mechanical function and a significant prolongation in survival time (56.9 +/- 2.6 minutes. P less than 0.01). Glycogenolysis was enhanced and levels of key glycolytic intermediates were reduced, suggesting an acceleration of glycolytic flux. Excess levels of pyruvate (1.52 +/- 0.48 mumol/ml of coronary perfusate) provided added substrate for oxidation and led to a greater than 5-fold incrase in rates of pyruvate decarboxylation as compared to untreated ischemic hearts...
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PMID:Effects of treatment with pyruvate and tromethamine in experimental myocardial ischemia. 95 68

Infusion of glucose alone or glucose with insulin in cats subjected to acute myocardial ischemia did not alter the hemodynamic response of the cats to coronary artery ligation. Furthermore, determination of myocardial creatine phosphokinase (CPK) (ATP:creatine N-phosphotransferase, EC 2.7.3.2) activities failed to reveal a protective effect of glucose and insulin upon the status of the developing infarct in the ischemic myocardium. However, glucose and insulin apparently promote clearance of CPK from the plasma and inhibit proteolysis during the early phase of myocardial ischemia. These actions may be of value in generalized adaptive response of the animal to the stress of ischemia, but does not per se appear to diminish the spread of the ischemic damage within the heart not to limit the extension of the evolving infarct.
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PMID:Lack of a significant protective effect of augmented circulating glucose on the ischemic myocardium.BJ. 97 70

We evaluated hyperthermic influences on ischemic hearts by comparing two groups of intact working swine hearts (n = 20) made globally ischemic. Heart muscle temperature was selectively increased from 37.5 +/- 0.3 degrees C to 39.7 +/- 0.3 degrees C in one group (n = 11) by warming the coronary perfusate. Ischemia in normothermic hearts significantly (P less than 0.05) decreased mechanical function (as reflected by increases in left ventricular end-diastolic pressure [LVEDP]), myocardial oxygen consumption (MVO2), glucose uptake, glycolytic flux, free fatty acid (FFA) uptake and oxidation, and tissue stores of high energy phosphates. Hearing in ischemic hearts further depressed mechanical function at similar reductions in coronary flow and MVO2. Glucose uptake was terminally increased over normothermic values (329 vs. 221 mumol/hr per g) as was glycolytic metabolism, FFA uptake (26 vs. 17 mumol/hr per g), and FFA oxidation (21 vs. 11 mumol/hr per g). However, these changes were not translated into increased energy stores of tissue creatine phosphate and ATP. Thus, in ischemic hearts, hyperthermia neither prevented the development of mechanical deterioration nor improved oxidative phosphorylation despite increases in metabolic substrate utilization. These data suggest that in experimental global ischemia heat is an added energy drain in already burdened myocardium.
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PMID:Effects of hyperthermic stress on myocardial function during experimental coronary ischemia. 97 53

The perfused rat heart was used to assess the possible contribution of glycolytically produced ATP to the maintenance of the action potential in the normoxic heart, and to the maintenance of membrane integrity in the underperfused, ischemic heart. During normoxia, pyruvate (10 mM) was nearly as able as glucose (10 mM) to maintain the normal action potential. During ischemia (reduction of perfusion pressure of Langerdorff heart from 100 to 20 cm H2O), total tissue values of ATP and creatine phosphate were similar in pyruvate and in glucose hearts. However, pyruvate-perfused hearts had higher tissue levels of cyclic AMP during the ischemic period, and during the reperfusion period they had an increased release of lactate dehydrogenase and an increased incidence of arrhythmias when compared with glucose hearts. It is proposed that these differences can be related to a higher rate of production of glycolytic ATP. The anatomical, biochemical, and pharmacological evidence favoring a cytoplasmic compartment of ATP located in relation to the cell membrane is reviewed.
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PMID:Glycolytic ATP and its production during ischemia in isolated Langendorff-perfused rat hearts. 103 48

Pacing-induced myocardial ischemia in 18 patients resulted in an increase of coronary sinus hypoxanthine levels from 1.20 +/- 0.18 micron during control to 2.41 +/- 0.52 micron (p less than 0.025) during pain. In addition, early lactate production occurred frequently before angina was noted. Neither hypoxanthine nor lactate levels changed in seven nonanginal patients, nor were significant alterations in potassium, inorganic phosphate, glucose, or oxygen saturation found in all patients. Myocardial hypoxanthine production seems a useful indicator of ischemia in the human heart.
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PMID:Changes in purine nucleoside content in human myocardial efflux during pacing-induced ischemia. 103 94

The fetal mouse heart (FMH) in organ culture continues to beat for a period of weeks, but degenerative changes occur. Electron microscopy revealed formation of autophagic vacuoles containing damaged organelles in some cells after the first day, indicating focal cytoplasmic injury. This process was accelerated by transient deprivation of oxygen and glucose followed by resupply of oxygen and glucose. FMHs were maintained for up to four hours in glucose-free media in an atmosphere of 95% N/5% CO2 followed by resupply of O2 and glucose. Twenty-four hours later, many cells recovered without residual injury. Many others revealed autophagic vacuoles ranging from those in which organelles were readily identified to those characteristic of residual bodies. It appears that focal injury stimulates the endoplasmic reticulum to enclose the damaged components, permitting localized lysosomal digestion without causing injury to the entire cell. Autophagy has not been emphasized as an important mechanism in transient ischemia in adult myocytes, but it may play a role in repair of sublethal injury. The FMH organ culture provides an excellent model for studying the sequential autophagic changes in a system in which these events can be accelerated.
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PMID:Autophagy in cardiac myocytes. 103

The role of arterial blood flow in hepatic metabolic functions was compared to that of portal flow in two groups of totally depancreatized dogs. Survival times and glucose and nitrogen excretion were significantly greater in dogs with ligation of the hepatic artery than in dogs with an Eck fistula. The dogs with ligated hepatic arteries also showed a significantly slower rise in plasma ketones. The course of diabetes was compared in three additional groups of partially depancreatized dogs consisting of a) dogs with ligated hepatic arteries, b) dogs with Eck fistulas, and c) controls. Hepatic arterial ischemia: 1) increased survival, without insulin treatment (a--650, b--167, c--124 days) 2) did not decrease tracer-determined rate of glucose production 3) led to a greater urinary excretion of glucose, ketone bodies and nitrogen than portal ischemia. Partially depancreatized dogs with either arterial or portal hepatic ischemia maintained a high rate of glucose disappearance on acute deprivation of endogenous insulin (clamping of vessels of their pancreatic remnant) due probably to decreased insulin degradation by the ischemic liver. The dogs died in coma after losing all fat depots. There was severe fatty change in the livers of dogs with hepatic artery ligation, slight in those with Eck fistulas and no fat in the livers of controls.
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PMID:Effects of arterial or portal ischemia on survival and metabolism of partially and totally depancreatized dogs. 105 92

A new experimental model for the study of two important aspects of ischemia, namely, oxygen and substrate deprivation, is proposed: the intact, beating fetal mouse heart in organ culture. This model offers long-term stability, ease and reproducibility of preparation, and the ability to manipulate experimental conditions. Hearts deprived of oxygen and glucose ceased beating immediately. After 3-4 hr of deprivation, biochemical and ultrastructural changes consistent with ischemic injury were evident. These include depletion of ATP and glycogen levels, loss of cytoplasmic enzymes, and extensive swelling and disruption of mitochondrial structure. Glucose and insulin partially protected against ATP depletion. Upon resupply of oxygen and glucose , beating resumed immediately, ATP levels rapidly increased to control levels and, consistent with this, mitochondrial structure returned toward normal. During the recovery phase autophagic vacuoles containing damaged mitochondria and myofibrils were seen, indicating that repair mechanisms were activated. Consistent with this, the proportion of lysosomal enzymes that were present in the nonsedimentable fraction of the tissue homogenate increased. We conclude that the cultured fetal mouse heart is a model useful for studying myocardial responses to anoxia and/or substrate deprivation and for assessing interventions designed to limit damage or to stimulate repair after ischemic injury.
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PMID:Fetal mouse hearts: a model for studying ischemia. 105 96

The author describes a family (48 year old mother and 15 year old son) with the muscular variant of glycogenosis-McArde's metabolic myopathy. The mother has been ill since 22 years old, the son--since 7. The disease had a slowly progressive development. The clinical picture was characterized by convulsions of the type of cramps following physical loadings on muscles of the body and extremities. Convulsions were accompanied by pain, an induration and enlargment of the muscles, muscle fatigue and increased significantly in an artifical ischemia of the extremities. A histochemical study of the muscle revealed a pathological accumulation of glycogen. The content of lactic and pyruvic acid in the blood after work in ischemic conditions did not change significantly. A study of the sugar curve in the blood with a loading with glucose and a parallel determination of insulin by a radioimmune method found hyperinsulinemia and a dysfunction of the pancreas.
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PMID:[McArdle's disease (a familial case)]. 106 64

The effect of intravenous infusion of 10 per cent glycerol on regional cerebral blood flow (using hydrogen bolus and Xenon-133 (133Xe) clearance methods) and metabolism was investigated in 57 patients with recent cerebral infarction. Hemispheric blood flow (HBF) increased, together with increase in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV), in foci of brain ischemia. Hemispheric oxygen consumption (HMIO2) decreased together with hemispheric respiratory quotient. Systemic blood levels of glucose, lactate, pyruvate, and triglycerides also increased after glycerol while free fatty acids (FFA) and inorganic phosphate (Pi) decreased. Hemispheric glucose consumption was unaltered after glycerol so that hemispheric glucose to oxygen ratio tended to rise. Pyruvate and lactate production by brain was unchanged. Glycerol moved across the blood brain barrier into brain and cerebrospinal fluid (CSF). Release of FFA and Pi from infarcted brain was reversed by glycerol. Total phosphate balance was maintained actoss brain both before and after glycerol infusion. Triglycerides increased in CSF after glycerol, originating either from cerebral blood or as a result of lipogenesis in cerebral tissue. The EEG Recording and neurological status of the patients improved despite decreased brain oxygen consumption. Results of this study suggest that after intravenous infusion of 10 per cent glycerol in patients with recent cerebral infarction, glycerol rapidly enters the CSF and brain compartments and favorably affects the stroke process in two ways: first, by redistribution of cerebral blood flow with increase in rCBF and rCBV in ischemic brain secondary to reduction in focal cerebral edema; and second glycerol may become an alternative source of energy either by being directly metabolized by the brain, or indirectly, by enhancing lipogenesis, or by both processes. Involvement of glycerol in lipogenesis with esterification to accumulated FFA might lead to improved coupling of oxidative phosphorylation, a hypothesis that fits the finding of improved neuronal function despite further decrease in cerebral hemispheric oxygen consumption.
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PMID:Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction. 109 Mar 93


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