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

We investigated the temporal and spatial development of infarcts in porcine hearts to evaluate the time-dependent beneficial effect of reperfusion on infarct size. The left anterior descending coronary artery (LAD) was occluded in 17 pigs for different periods of time followed by 4 hours of reperfusion. Transmural needle biopsies subdivided into subendocardial and subepicardial halves were taken from the ischemic apex after 60 min of ischemia to determine the tissue concentrations of ATP and NAD. The myocardium-at-risk was assessed with a fluorescent dye injected into the right atrium at the end of the experiments, just after the LAD had been reoccluded. The excised hearts were cut into slices parallel to the heart basis. The ischemic myocardium was measured by planimetry of the non-fluorescent areas whereas the infarcted tissue was determined with the NBT stain and related to the area-at-risk. Ischemic cell death started in the jeopardized left ventricular subendocardial septum after about 30 min of ischemia. The further progress involved the right subendocardial septum and the subendocardium of the left anterior free wall. Already after 75 min of ischemia most of the myocytes-at-risk were irreversibly injured. Infarctions reached their final extent after 90-120 min of ischemia. These results indicate that in hearts without a significant collateral blood flow reperfusion can only reduce infarct size if its initiated within 60-75 min of ischemia. Like in canine hearts infarctions progress from the ischemic subendocardium towards the outer layers.
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PMID:Temporal and spatial development of infarcts in porcine hearts. 648 36

The effects of 3 hours of ischemia and 1 hour of reperfusion on biochemical, physiological and ultrastructural parameters were studied in 12 dogs. In the ischemic subendocardium without reperfusion, mitochondrial losses of adenine (ATP + ADP + AMP) and pyridine (NAD + NADH) nucleotides far exceeded those observed in whole tissue. Adenine nucleotide translocator (ANT) was severely inhibited and seemed to be a sensitive indicator of a lesion of the inner mitochondrial membrane. Postischemic reperfusion led to a slight loss of adenine and pyridine nucleotides from the reversibly damaged subepicardium and to an enormous loss from the irreversibly damaged subendocardium. The washout of nucleotides from irreversibly damaged areas caused the negative para-Nitro Blue Tetrazolium ( pNBT ) staining of the infarcted tissue. Diagnosis of cell death with pNBT failed after the occlusion period without reflow because pyridine, although lost from the mitochondria, was still present in the tissue. In reversibly injured areas, mitochondrial function and ultrastructure were restored after reperfusion, although a significant nucleotide loss was found in the tissue. These studies suggest that mitochondrial ultrastructure and function may play a key role in cellular viability during recovery from ischemia.
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PMID:Mitochondrial damage during myocardial ischemia. 674 90

The effects of myocardial ischemia and reperfusion on pyruvate dehydrogenase (PDH) activity were studied in isolated rat hearts. PDH remained largely (80%) in the active form during 10 min of whole heart ischemia in hearts receiving 11 mM glucose as substrate. With reperfusion, PDH was converted to the inactive form (45% by 2 min) and then returned slowly to control levels. Addition of pyruvate (10 mM) to the glucose containing perfusate during reperfusion prevent the reperfusion inactivation of PDH (96% active). The maintenance of a high percent of PDH in the active form during ischemia occurred in spite of high mitochondrial ratios of NADH/NAD and acetyl CoA/CoA and was related to a very low mitochondrial ATP/ADP ratio. The low ATP and high ADP would restrict PDH kinase phosphorylation and inactivation of PDH during ischemia. Reperfusion resulted in a rapid increase in mitochondrial ATP/ADP ratio and the increased availability of ATP as substrate for the kinase coupled with continued high levels of NADH and acetyl CoA which stimulate kinase activity may have accounted for the early inactivation of PDH with reperfusion. Addition of pyruvate to the perfusate probably inhibited the PDH kinase and prevent the reperfusion inactivation of PDH.
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PMID:Effects of ischemia and reperfusion on pyruvate dehydrogenase activity in isolated rat hearts. 687 85

The effects of ischemia on in vivo fatty acid metabolism in fetal lung were studied using rabbit fetuses of 25 to 28 gestational age. Ischemia was produced by inflating the aortic balloon thereby reducing the uterine blood flow. Ischemic insult resulted significant increase in lactate/pyruvate and NADH/NAD ratios and decrease in ATP/ADP ratio in fetal lung. Levels of CoA, acetyl CoA, carnitine and acetyl carnitine decreased while those of long chain acyl CoA and long chain acyl carnitine enhanced. Tissue content of these metabolites returned to normal after 2 hr stabilization following 20 min of ischemic insult. Ischemia also caused small increase in lipogenesis and neutral lipid content of fetal lungs. Our results thus suggest that beta-oxidation in fetal lung is inhibited and becomes rate-limiting for fatty acid oxidation during ischemia. Sudden occurrence of hypoxia or ischemia in the fetus is a typical challenge for the obstetricians. The patients occasionally suffer from neurological injury following cerebral hypoxemia. The hypoxic insult may also affect the respiratory activity significantly. For example, acute alveolar hypoxia causes pulmonary vasoconstriction by damaging pulmonary vascular smooth muscle (1) and results in reduction of fatty acid oxidation by limiting the ATP supply required for metabolic processes (2). Hypoxia has also been shown to decrease the rate of palmitate incorporation into phospholipids (3), inhibit rate of fatty acid synthesis (3) and depress rate of incorporation of fatty acid and phosphatidic acid into lipids (4). Despite the fact that fatty acids represent a major substrate for energy metabolism in lung, no work has been done on the fatty acid metabolism in fetal lung. The present study was designed to determine the fate of fatty acid oxidation in fetal lung during ischemic challenge. The levels of acyl CoA and acylcarnitine intermediates were also measured in order to determine the rate-controlling steps of fatty acid metabolism in the fetal lung.
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PMID:Effect of ischemia on fatty acid metabolism in fetal lung. 688 85

Cerebral ischemia was induced in cats using bilateral carotid artery occlusion coupled with hemorrhagic hypotension. Thirty minutes of ischemia, which depleted levels of ATP and phosphocreatine throughout the cerebral cortex, was followed by 2-4 hours of recirculation. During the recovery period, cortical perfusion and NADH fluorescence were monitored through a cranial window. Postischemic perfusion, as indicated by transit time, was initially higher than control, but declined to subnormal levels by 60 minutes. NADH fluorescence transients, induced by brief anoxia, also decreased steadily during recirculation, indicating a failure of oxidation-reduction capability. The disappearance of anoxic-NADH transients usually preceded the decline of flow, suggesting that O2 delivery was not the factor limiting redox reactions. Furthermore, tissue levels of NADH, which were nearly normal after 2-4 hours of recirculation, did not indicate tissue hypoxia. In spite of normalization of NADH, resynthesis of high energy phosphates were severely impaired. The degree of ATP recovery varied widely in different cortical regions; however, there were two general groups of ATP values--one at 5% and the other at 70% of control levels. In the energy-depleted areas, NADH levels were normal, but the total pool of NAD (NADH + NAD+) and the tissue content of K+ were 43% lower than control. In contrast, the NAD pool and K+ content were only slightly diminished in the regions with greater ATP restitution. The results suggest that postischemic resynthesis of ATP may be limited not by inadequate delivery of O2, but rather by defective production of NADH.
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PMID:Factors limiting regeneration of ATP following temporary ischemia in cat brain. 706 95

The cellular levels of adenine nucleotides and their metabolites in ischemic rat liver were assayed by high pressure liquid chromatography with high theoretical plate numbers. The method was sensitive enough to measure all the metabolites in about 1 mg of tissue, and to examine changes in their levels in a single liver in ischemia. In ischemia the cellular level of ATP decreased rapidly. Concomitantly there was a transitory increase in AMP, followed by its degradation to allantoin via adenosine with accumulation of all species of purine catabolites. NAD was also degraded gradually with concomitant accumulation of nicotinamide. Thus, the level of total adenine nucleotides decreased during ischemia and the amount of this decrease ws equal to the sum of the amounts of catabolites produced. The ATP level was rapidly restored on recirculation after an ischemic period of less than 15 min. However, recovery of the ATP level was depressed by prolonged ischemia and was not observed after an ischemic period of 2 h. Intermediate purine catabolites that accumulated in ischemia were also cleared during recirculation either by their removal in the blood flow or by further oxidative degradation, but they were not salvaged for reuse until the cellular level of ATP was restored. Administration of allopurinol resulted in marked accumulation of hypoxanthine in ischemic liver, but neither this drug nor chlorpromazine had any appreciable effect on recovery of the ATP level during recirculation.
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PMID:Changes in cellular levels of ATP and its catabolites in ischemic rat liver. 709 91

Nicotinamide adenine dinucleotide (NADH) kinetics were measured in 76 cortical areas in 26 patients with transient ischemic attacks (TIAs) undergoing extracranial-intracranial bypass. Direct cortical stimulation was utilized to induce changes in surface fluorescence corresponding to a brief oxidation and reduction of mitochondrial NADH. Preoperative studies of cerebral blood flow in gray matter (CBF)g) demonstrated normal perfusion in 11 patients and ischemic changes ((CBF)g less than 43.5 ml/100 g/minute) in 15 patients. In 30 normally perfused areas within the craniotomy, the mean half-time for reduction (t1/2(red)) of cortical NAD was 21.5 +/- 2.6 seconds. In 39 ischemic areas, the mean t1/2(red) was 5.6 +/- 1.2 seconds. These rapid reduction rates were associated with supernormal overshoots of the base line indicative of a transient oxygen debt. Kinetic responses could not be elicited from 7 areas adjacent to foci of decreased attenuation on compound tomography. Bypass resulted in normalization of the t1/2(red) in 24 of 28 areas of ischemia. The dependence of NADH kinetics on blood flow through the graft was demonstrated in 15 of 19 areas of mild ischemia by the reapplication of a clip to the donor artery. It is concluded that persistent reversible abnormalities of cortical mitochondrial metabolism exit in a significant number of patients with a history of TIAs who are suitable candidates for bypass surgery. In such patients bypass may effectively augment the nutrient supply to meet the bioenergetic demands associated with increased electrophysiological activity.
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PMID:Cortical nicotinamide adenine dinucleotide (NADH) kinetics in patients undergoing extracranial-intracranial bypass. 709 92

It was shown on the DS-carcinosarcoma of rat that NAD-induced blood pressure reduction to 50% of the initial value is followed by a selective compression ischemia in the tumor tissue. In this period that can be prolonged to at least 10 min by infusion of NAD the microcirculation in the tumor tissue is almost completely inhibited. Determinations of the blood volume confirm the results obtained bei O. D. measurements. The significance of this finding and its eventual utilization (cancer therapy) are discussed.
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PMID:[Selective inhibition of microcirculation in tumor tissue by manipulated blood pressure reduction]. 714 10

Reperfusion after global ischemia (10-60 min in duration) in rat neocortex most commonly provoked transient hyperoxidation of mitochondrial electron carriers, tissue hyperoxygenation, and CBF hyperemia. These responses were normally accompanied by recovery of K+ homeostasis and EEG spike activity. Goals of this research were to understand putative relationships among these postreperfusion events with special emphasis on determining whether mitochondrial hyperoxidation results from intracellular changes that may modulate residual damage. The amplitude of postischemic mitochondrial hyperoxidation (PIMHo) did not increase when CBF increased above an apparent threshold during reperfusion, and tissue hyperoxygenation was not required for PIMHo to occur or to continue. These findings suggest that PIMHo is not merely a response to increased CBF and tissue hyperoxygenation; rather, PIMHo is modulated, at least in part, by residual intracellular derangements that limit mitochondrial electron transport. This suggestion was supported by observations that NAD became hyperoxidized after reoxygenation in anoxic hippocampal slices. Also, PIMHo occurred and subsequently resolved in many animals, but K+o never was cleared fully to baseline and/or EEG spike activity never was evident. One suggestion is that PIMHo signals or initiates residual intracellular derangements that in turn impair electrical and metabolic recovery of cerebral neurons after ischemia; an alternative suggestion is that PIMHo and tissue hyperoxygenation are not the sole factors modulating the immediate restoration of electrical activity after ischemia. Present data also support the following: Decreased oxygen consumption, despite adequate oxygen delivery, likely contributes to tissue hyperoxygenation after ischemia; and mitochondrial hyperoxidation is modulated by a limitation in the supply of electrons to the mitochondrial respiratory chain.
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PMID:Mitochondrial hyperoxidation signals residual intracellular dysfunction after global ischemia in rat neocortex. 779 Apr 15

The present study deals with the in vitro and in vivo effects of methyl isocyanate (MIC) on rat brain mitochondrial function. Addition of MIC to tightly coupled brain mitochondria in vitro resulted in a mild stimulation of state 4 respiration, abolition of respiratory control, decrease in ADP/O ratio, and inhibition of state 3 oxidation. The oxidation of NAD(+)-linked substrates (glutamate + malate) was more sensitive (fourfold) to the inhibitory action of MIC than succinate while cytochrome oxidase was unaffected. Administration of MIC subcutaneously at a lethal dose affected respiration only with glutamate+malate as the substrate (site I) and caused a 20% decrease in state 3 oxidation leading to a significant decrease in respiratory control index while state 4 respiration and ADP/O ratio remained unaffected. As both the malondialdehyde and iron contents of brain mitochondria were not altered, it may be inferred that the observed in vivo inhibition of state 3 oxidation is induced by MIC through systemic stagnant hypoxia leading to ischemia of brain, which further contributes to the cerebral hypoxia.
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PMID:In vitro and in vivo effects of methyl isocyanate on rat brain mitochondrial respiration. 806 Jan 73


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