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

The relationship between energy metabolism and the extent of irreversible ischemic damage was examined in an isolated perfused working rat heart. The amount of cardiac work recovered after reperfusion of hearts exposed to severe global ischemia was dependent upon both the duration of ischemia and the type of substrate provided (either 5 mM glucose or 5 mM glucose + acetate). There appear to be two distinct phases in the ability to recover mechanical function in the reperfused ischemic heart. The second phase corresponds to the onset of severe irreversible tissue damage. Irreversible mitochondrial damage was not found to correspond with the onset of heart failure since the ATP/ADP ratio remained constant in the reperfused myocardium. Furthermore, there does not appear to be a direct correlation between the total ATP content and the extent of irreversible damage, either during ischemia or following reperfusion. However, the total adenine nucleotide content during ischemia showed dramatic changes which correspond temporally with the initiation of the second phase of damage. The observation that the adenine nucleotide pool becomes further depleted during reperfusion suggests that alterations in the salvage pathway for adenine nucleotide synthesis have occurred. Loss of adenine nucleotides appears to be an excellent marker for irreversible heart failure. Acetate provides some protection the the ischemic myocardium. The mechanism by which acetate mediates this protective effect is discussed.
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PMID:Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart. 44 6

In order to investigate possible differences in the reaction to hypoxic conditions between "red" and "white" skeletal muscle, cats were subjected to a 2 h period of either hemorrhagic shock or hind limb tourniquet ischemia, and the hypoxia induced changes were studied in the soleus and lateral gastrocnemius muscles. Muscle biopsies were analysed for ATP, CP, glucose, G 6-P and lactate. Using microelectrodes, the resting membrane potential was repeatedly measured. Both experimental models resulted in increased tissue lactate levels and a successive decrease in the membrane potential of both muscles studied. No reduction of the high energy phosphagen content (ATP + CP) occurred in any of the muscles during shock. The tourniquet ischemia resulted in a 40% reduction of the ATP + CP content in the soleus muscle, whereas in the gastrocnemius muscle no significant reduction occurred. A significant correlation was found between the tissue lactate content and the membrane potential under both conditions and in both muscles studied. It is concluded that "red" muscles are more susceptible to metabolic derangement than "white" muscles during total ischemia, whereas during hypovolemia "red" muscles appear to be protected from early hypoxic damage, probably due to a redistribution of skeletal muscle blood flow.
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PMID:Metabolic responses in feline "red" and "white" skeletal muscle to shock and ischemia. 46 77

Effects of chronic denervation upon in vivo forearm metabolism were studied in six patients and six controls. The diagnosis was amyotrophic lateral sclerosis in four patients, the neuronal form of Charcot-Marie Tooth disease in one patient, and an unclassified chronic disease of the lower motor neurons in one patient. In all cases the forearm muscles showed clinical weakness and electrical evidence of denervation, while muscle biopsy from a proximal muscle of the upper limb showed typical denervation atrophy. At rest there was increased oxygen utilization and lactate output as well as a tendency for increased uptake of glucose and long chain fatty acids from arterial blood per 100 ml of forearm tissue. During exercise the abnormally high lactate output increased further. An increased arterial lactate concentration was present during rest and exercise. Oxidation of fatty acids was not impaired. It is suggested that these abnormalities are consistent with an augmented utilization of blood borne fuels at rest by denervated muscles. A concurrent regional ischemia of muscles during rest and exercise, possibly due to defective autoregulation of skeletal muscle blood flow, may explain the abnormally high lactate generation.
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PMID:The effects of partial chronic denervation on forearm metabolism. 48 96

In an isolated rat liver perfusion system the effects of normothermal ischemia on hepatic functions were investigated. After 30 minutes of anoxy bile production and BSP elimination capacity of the liver are significantly reduced. The quantity of secreted "ascites" from the surface of the liver several times high after anoxic damage, while oxygen consumption, portal venous pressure and ammonia elimination do not differ significantly from the controls. Pretreatment with insulin plus glucose, isoproterenol, hypoxanthine, chlorpromazine and glucagon (5 micrograms/100 g i.v., or 0.2 mg/100 g s.c.) does not reduce noticeably the normothermal anoxic lesion of the liver Glucagon (50 micrograms/100 g i.v.), allopurinol, dibenzyline, ATP-MgCl2 and aspartic acid enhance significantly the ischemia-tolerance of liver in vitro.
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PMID:Ischemic damage of the liver. Part I: In vitro investigation of the prevention of the ischemic lesion of the liver. 49 24

Progressive cerebral ischemia was induced by blood pressure (BP) reduction in rats during status epilepticus, and the sequence of cerebral functional (EEG, extracellular K+ activity) and metabolic (levels of high energy phosphates, glucose, glucose-6-phosphate, lactate, pyruvate, alpha-ketoglutarate) changes were determined. Very moderate reductions of BP were accompanied by tissue lactate accumulation and a decrease of the rate of re-uptake of K+ extruded during discharges. These changes were pronounced at BP about 50 mm Hg, when also the energy state showed some deterioration, and the EEG activity changed from one of bursts and suppressions into single spikes. At BP about 30 mm Hg EEG activity was abolished, but not until a slightly lower BP level was there a severe energy depletion and a massive K+ release, indicating generalized membrane depolarization. The results show an increased susceptibility to ischemia during seizures with changes of membrane pump function, and energy metabolism appearing at moderate reductions of BP. Concomitant decrease of seizure activity delayed to some extent the development of massive energy failure and membrane depolarization.
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PMID:Effects of reduced cerebral blood flow upon EEG pattern, cerebral extracellular potassium, and energy metabolism in the rat cortex during bicuculline-induced seizures. 49 17

The effect of repeated local ischemia and reperfusion on myocardial metabolism and ventricular performance was studied in 12 open-chested pigs fasted overnight. Myocardial ischemia was induced by reduction of the flow in the left anterior descending coronary artery to 40% of control during 30 min. After 35 min of reperfusion a second 30-min occlusion period was started, again followed by a 35-min reperfusion period. At the end of both reperfusion periods coronary flow and coronary resistance had returned to control values. During control there was lactate uptake, but no significant uptake of glucose, free fatty acids (FFA), triglycerdies, glycerol and inosine. During the first occlusion period the heart released lactate and inosine, and used glucose and FFA. At the end of the first reperfusion period lactate uptake approached control values, but inosine was still released by 10 of the 12 animals. In the second ischemic period, glucose and FFA were again taken up. Lactate and inosine were released, but the production was much smaller than during the first occlusion period. Depletion of myocardial glycogen and high-energy phosphates could be responsible for this quantitatively different response. Necrosis may have played a role, although enzyme release was minimal and only observed after the second occlusion period. Heart rate, peripheral resistance and ventricular filling pressure were virtually unchanged throughout the course of the experiments. Maximum rate of fall of left ventricular pressure (min LVdP/dt) decreased during ischemia and did not recover during reperfusion. Changes in min LVdP/dt and cardiac output were more closely related than changes in max LVdP/dt and cardiac output. This model cannot be used for the study of interventions during myocardial ischemia in which the animal serves as its own control.
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PMID:Myocardial substrate utilization and hemodynamics following repeated coronary flow reduction in pigs. 52 55

Primary cultures of rat heart endothelial cells were subjected to simulated conditions of ischemia: hyposia and glucose deprivation for 4 and 24 hr. Cellular injury was evaluated by measuring changes in viability, total protein, cellular morphology, and leakage of cytoplasmic enzymes from the cells into the culture medium. Deprivation of oxygen and glucose for 4 or 24 hr did not lethally injure the cells as noted by no change in cell viability, morphology, and total protein when compared to controls. However, reversible or non-lethal cellular injury was produced as reflected by a significant release of lactate dehydrogenase (LDH) from the cells into the medium after treatment with hypoxia and glucose deprivation for 4 or 24 hr. When the cultures were deprived of glucose, but were oxygenated, cellular injury was not evident after 24 hr. Deprivation of oxygen but not glucose resulted in significant loss of LDH after 4 or 24 hr. When the cultures were allowed to recover after oxygen and glucose deprivation in complete medium containing 1000 mg glucose per 1 and a normal atmosphere of 20% O2, they had levels of LDH leakage comparable to those of control cultures.
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PMID:Injury to primary cultures of rat heart endothelial cells by hypoxia and glucose deprivation. 54 Sep 18

A reduction in myocardial oxygen supply during ischemia, not only leads to reduced aerobic ATP production but does not stimulate glycolytic ATP synthesis. The residual aerobically synthesized ATP comes primarily from continued inefficient (i.e., compared to glucose in terms of moles of ATP produced per mole of O2 consumed) oxidation of fatty acids. This leads to elevated tissue levels of long chain fatty acyl-CoA and fatty acyl-carnitine. Both are potentially cell damaging metabolic intermediates. Restriction of glycolysis is due to inhibition of glyceraldehyde-3-phosphate dehydrogenase by accumulated metabolites, such as H+, lactate and NADH. The reduced production of ATP leads to decreased levels of high energy phosphate stores which in turn may impair myocardial mechanical function.
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PMID:Energy metabolism in the ischemic heart. 55 21

Sensory conduction along the median nerve was evaluated during 30 minutes of ischemia in patients with diabetes mellitus. There was abnormal persistence of the sensory evoked potential in 19 of 22 diabetic patients, but not in normal controls, patients with nonmetabolic neuropathies, or 5 of 6 patients with motor neuron diseases. There was an excellent correlation between ischemic resistance and effective control of glucose metabolism, as manifested by Hb A1C levels. These data suggest that abnormal ischemic resistance in diabetes may be the most sensitive indicator of peripheral neural dysfunction even when there are no other electrophysiologic or clinical abnormalities.
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PMID:Ischemia and sensory nerve conduction in diabetes mellitus. 57 68

The effect of KoQ4 on the energetics, contractility, and electrogram of the ischemized myocardium was studied in acute experiments on dogs with induced myocardial ischemia. Intracornoary administration of KoQ4, 1.3 mg/kg, directly into the focus of ischemia for 15 min promoted a decrease in the lactate level in blood draining from the ischemic zone as compared to the control data in the absence of a difference in the dynamics of the pyruvic acid content. In distinction to the control experimental series, there was no decrease in the concentration of glucose in samples of venous blood draining from the focus of ischemia. Under the effect of KoQ4 the amplitude of left ventricular pressure and the maximum rate of its growth (dp/dt) increased moderately and the ST segment and ST/R coefficient of the epicardial electrogram from the border zone of ischemia decreased. It was shown in the rat experiments that preliminary intravenous administration of KoQ4 (14 mg/kg) increased myocardial resistance to oxygen deficiency under conditions of diacetylcholine-induced apnoe.
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PMID:[Effect of hexahydroubiquinone-4 (KoQ4) on the bioenergetics and functional activity of the myocardium in ischemia]. 59 31


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