Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative time courses of early changes in myocardial metabolism and function during anoxia, global ischemia, and regional ischemia were compared in isolated rat hearts. Transmural anoxic wave front was determined with NADH fluorescence photography, and oxygen saturation of myoglobin and dynamic systolic wall thickening were measured with spectrophotometry of light transmitted through the left ventricular free wall. In all three treatments, anoxic wave front first appeared in the subendocardium and reached the epicardial half of the myocardium in 10 s, when oxygen saturation of myoglobin decreased by 50% and tissue ATP and creatine phosphate remained at aerobic levels. During this period, systolic wall thickening decreased gradually in anoxia and global ischemia, whereas a marked decrease in systolic wall thickening and appearance of dyskinesia (wall thinning) occurred in regional ischemia. Thus the early extension of anoxic wave front and metabolic changes are similar with all three treatments, and dyskinesia, observed only in case of regional ischemia, occurs when the inner half is ischemic or anoxic.
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PMID:Transmural anoxic wave front and regional dysfunction during early ischemia. 361 98

Changes in microcirculation, the NAD/NADH redox state, and electrical activity during 2 hours of ischemia and 4 hours of reperfusion produced by middle cerebral artery occlusion and release were studied in cats. Twelve animals were classified into three groups of ischemia (mild, moderate, and severe) based on the severity of electrocorticographic (ECoG) depression at the end of the recovery period. Four animals were studied as controls. Occlusion of the middle cerebral artery (MCAO) resulted in a marked but similar degree of reduction in cerebral blood flow (CBF) in all three groups. After this initial change, CBF increased continuously during occlusion in the mild group. CBF in the moderate and severe groups remained at the same low level during the entire period of MCAO. Immediately after MCAO, NAD reduction was increased by approximately 50% in all groups. At the end of MCAO, while the NAD/NADH redox state returned to its pre-ischemic reference level in the severe group, it remained markedly reduced in the mild and moderate groups. Removal of the clip led to slight reactive hyperemia in the mild and severe groups but not in the moderate group. Immediately after recirculation, NAD/NADH redox was shifted toward oxidation in all groups. However, this reoxidation of NADH was only partial in the mild and moderate groups, and a pronounced hyperoxidation occurred in the severe group. In spite of the similar behavior of CBF in the recovery period, a marked secondary NAD reduction occurred in the moderate group during the recirculation period. It is suggested that this represents cessation of mitochondrial electron transport in the dying cells, accompanied by stimulated anaerobic glycolysis in other cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of microcirculatory, NAD/NADH, and electrocorticographic changes in cat brain cortex during ischemia and recirculation. 372 9

Voltage-sensitive dyes were used to stain intact perfused hearts and to simultaneously measure optical action potentials (APs) from 124 sites on the epicardium. Patterns of electrical depolarization (activation) and repolarization (recovery) along the surface of the heart were determined from the upstrokes and repolarization phases of optical APs. Standard surface extracellular techniques can detect electrical activation but not the recovery or the duration of APs. The optical recordings were previously shown to be equivalent to intracellular electrode measurements (Salama and Morad, Science Wash. DC 191: 485-487, 1976) and now reveal that AP durations are heterogeneous throughout the epicardium, with durations increasing from the base to the apex of the ventricles. In hearts beating under normal sinus rhythm, the direction and conduction velocity of the activation waves could be altered by electrical stimulation. The normal heterogeneities in AP durations became more pronounced in the presence of the Ca2+-entry blocker, verapamil. The local metabolic state of the tissue was also monitored optically through its intrinsic NADH fluorescence measured from 124 separate regions on the heart. The time course and extent of metabolic injury caused by general anoxia or by a local ischemia induced by a coronary ligation was monitored through maps of NADH fluorescence. The present technique makes it possible to correlate changes in the metabolic state of the muscle with detailed changes in patterns of electrical activity and thus provides a powerful new tool to study fundamental aspects of normal and abnormal cardiac rhythm.
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PMID:Maps of optical action potentials and NADH fluorescence in intact working hearts. 381 52

The effects of short- or long-term complete cerebral ischemia were studied in the gerbil brain using a multi-parameter monitoring system. Metabolic (NADH redox state) and hemodynamic responses were monitored by surface fluorometry-reflectometry. Ionic activities (K+ and pH) were measured by surface macroelectrodes. Electrical activity was evaluated by monitoring the general electrocorticogram (ECoG) as well as local DC steady potential (two sites). Two groups of gerbils were studied to compare the effects of 4-5 min occlusions with those of 30 min complete ischemia. During bilateral carotid artery occlusion the cortex is exposed to complete ischemia resulting in the complete depletion of O2 with attendant maximal reduction of NADH. Extracellular K+ began to increase as soon as energy reserves were decreased with a time course suggesting two different kinetic areas. Surface pH decreased very shortly after the occlusion. During the recovery phase, NADH was reoxidized soon after recirculation, whereas the pH and K+ recovery showed a short delay. ECoG did not recover even when all other parameters reached base-line levels. The recovery of all the measured parameters was correlated to the duration of the ischemic insult; i.e., the recovery from 30 min of ischemia took significantly longer than after 5 min of ischemia. We conclude that pH recovery depends on recirculation and adequate O2 supply to the tissue, whereas K+ recovery required not only an adequate O2 supply but also the integrity of the adenosine triphosphatase system.
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PMID:Metabolic, ionic, and electrical responses of gerbil brain to ischemia. 397 Jan 91

We have developed a hypoxia test by local ischemia, to be performed with a special probe adapted to an in situ NADH laser fluorimeter. Local ischemia is produced by pressurization on the organ surface in an area of approximately 0.2 mm2. In order to assess the method on open-chest rat hearts (ten), we used the following protocol: local ischemia tests (three), global anoxia (100% N2 ventilation), superimposition of local ischemia to global anoxia, and local ischemia tests during the period just prior to death and immediately thereafter. Three different responses were observed: large amplitude of compensated fluorescence (Fo) increase, medium amplitude of Fo increase, and no Fo increase. These responses were related to the metabolic state prior to the test (States 3, 4, and 5 of Chance's nomenclature). We have thus demonstrated the possibility of very rapidly determining the in situ NADH degree of reduction, without a destructive assay. Such a parameter may be of great relevance in heart surgery, as it might allow detection of potentially harmful situations, thereby enabling early and appropriate treatment.
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PMID:In situ monitoring of myocardial metabolism by laser fluorimetry: relevance of a test of local ischemia. 399 Apr 97

Effects of retrograde coronary venous perfusion on oxygen supply and energy metabolism of ischemic myocardium of the isolated perfused rat heart were examined by means of NADH fluorescence photography. Occlusion of the left coronary artery produced regional ischemia of the left ventricular free wall, as evidenced by the sharply demarcated increase in NADH fluorescence. During ischemia, a narrow area of minimal fluorescence (140 +/- 10 microns), indicating sufficient oxygenation for oxidative phosphorylation, was observed around the epicardial coronary veins in the ischemic lesion. Retrograde perfusion was introduced through the coronary vein (left cardiac vein) that drained off the ischemic area, which resulted in a marked reduction of the area of increased NADH fluorescence in the epicardial surface. In the cross-sectional view, although the myocardium of the entire ischemic area induced by left coronary artery occlusion could be perfused by venous retroperfusion, the effect on reduction of the area of increased NADH fluorescence was seen only in the epicardial half of the myocardium. Retrograde coronary venous perfusion also resulted in a small increase in tension development (P less than 0.05), a decrease in resting tension (P less than 0.01), and partial preservation of myocardial high energy phosphate content (P less than 0.01). We propose that coronary venous retroperfusion improves oxygenation, partially preserves oxidative phosphorylation in the epicardium, and improves contractile function in the ischemic region.
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PMID:Coronary venous perfusion of the ischemic myocardium during acute coronary artery occlusion in isolated rat hearts. 399 96

Hemodynamic and mitochondrial function recover following 60 minutes of ischemic arrest and reperfusion in hearts pretreated with verapamil. The present study was carried out to determine whether verapamil prevents the onset of mitochondrial oxidative impairment after 60 minutes of ischemic arrest without reperfusion. Two preparations of mitochondria isolated following Polytron homogenization and subsequent treatment of the myofibrillar pellet with Nagarse were examined for phosphorylating respiration. The Polytron mitochondria were more sensitive to ischemic arrest than were the Nagarse mitochondria with either glutamate-malate (57% vs. 22% inhibition), succinate (+ rotenone) (41% vs. 14% inhibition), or palmitoylcarnitine (57% vs. 27% inhibition) as respiratory substrates. Verapamil pretreatment significantly increased oxidation of all substrates by the subsequently isolated Polytron mitochondria, but only succinate-supported respiration returned to control levels. In contrast, the small amount of respiratory inhibition exhibited by the Nagarse mitochondria after ischemic arrest was insensitive to verapamil pretreatment. We conclude that the Polytron preparation of mitochondria is more susceptible to ischemia than the Nagarse mitochondria, and this susceptibility correlates with a striking sensitivity to verapamil protection. In general, oxidation of NADH-linked substrates, including palmitoylcarnitine, is more affected by ischemic arrest than succinate, and only oxidation of the latter substrate is totally protected by verapamil. The beneficial action of verapamil on mitochondrial function occurs prior to reperfusion. The data suggest that alterations in calcium homeostasis occur during the ischemic period, as well as in the subsequent reperfusion period.
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PMID:Protection of canine cardiac mitochondrial function by verapamil-cardioplegia during ischemic arrest. 399 98

Temporary focal cerebral ischemia was induced in 23 cats by occluding the left middle cerebral artery (MCA) for 2 h. Animals then were divided into groups for unforced reperfusion of varying duration ranging from 2 to 48 h. Regional blood flow (rCBF) at the borders of the ischemic area was measured repeatedly using the hydrogen clearance technique, and neurological ratings were obtained, both during ischemia and reperfusion. At the scheduled end of reperfusion brains were frozen in situ with liquid nitrogen, and regional distributions of biochemical substrate contents as well as tissue pH were visualized using bioluminescence and fluorescence techniques. During focal ischemia collateral flow in the border zone dropped to 55 +/- 20.3% of control level, and all animals developed a neurologic deficit with a median of 6 points on a disability scale from 0 to 10, rCBF and functional impairment being closely correlated (tau = -0.47, P1 less than 0.005). After reopening of the MCA there was an immediate and rather uniform increase in border zone flow to 105 +/- 25.7% of control level, while neurologic recovery was quite variable. In all but one animal reversible ischemia led to persistent disturbances in the energy-producing metabolism as demonstrated by the low regional ATP content, which in part was accompanied by a diminished NADH fluorescence and an alkaline pH shift at high tissue glucose levels. These findings suggest that disturbances in cerebral energy metabolism induced by temporary ischemia may be caused by inhibition of the glycolytic pathway that is hardly reversed by unforced reperfusion and, therefore, results in permanent damage.
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PMID:Neurologic deficit, blood flow and biochemical sequelae of reversible focal cerebral ischemia in cats. 400 1

Regional changes of brain tissue pH and its correlation to energy metabolism were studied in various degrees of incomplete ischemia for 5 and 60 min in the unilateral common carotid occlusion of normally fed mongolian gerbils. The degree of ischemia was evaluated by the severity of neurological deficits following 60 min of occlusion, and animals were divided into three groups: symptomatic, borderline, and asymptomatic. Changes of NADH and ATP distribution corresponded well to the degree of ischemia. On the other hand, acidosis developed more clearly and extended in wider areas than the changes of NADH and ATP distribution. These changes were already seen at 5 min of occlusion. From the results of this experiment, it was suspected that acidosis in mild incomplete ischemia was due to stimulated anaerobic glycolysis that might supplement NADH oxidation and ATP yields. Further, acidosis without energy failure was considered not to be detrimental to neuronal cells.
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PMID:Brain tissue acidosis and changes of energy metabolism in mild incomplete ischemia--topographical study. 403 Sep 20

Levels of energy metabolites were measured in forebrain regions in fasted rats subjected to 4-h recirculation after 1 h of either incomplete or complete ischemia. Both models of ischemia were produced by a procedure combining bilateral common carotid artery occlusion, systemic hypotension, and CSF pressure elevation; the degree of intracranial hypertension was varied to produce incomplete and complete ischemia. Levels of brain lactate at the end of ischemia ranged from 16 to 19 mmol/kg in incomplete ischemia and from 11 to 13 mmol/kg in complete ischemia. Energy metabolism recovered evenly in the neocortical and subcortical regions with recirculation after incomplete ischemia. The metabolic recovery in the cerebral cortex after complete ischemia was similar to that observed after incomplete ischemia; however, recovery in the subcortical regions after complete ischemia was less extensive, NADH fluorescence remained high, and there was a fall in total creatine. Intracellular pH in the dorsal thalamus was more alkalotic after complete than incomplete ischemia. Thus, in the absence of profound tissue lactic acidosis, residual CBF during prolonged ischemia helps postischemic restitution of brain energy metabolism in subcortical regions. The pattern of poor recovery in these regions after complete ischemia suggests inadequate reperfusion. The decreased total creatine and the severe tissue alkalosis may be biochemical markers of advanced tissue injury during reflow.
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PMID:Regional brain energy metabolism after complete versus incomplete ischemia in the rat in the absence of severe lactic acidosis. 405 23


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