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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

We have developed the multiprobe assembly (MPA) by which metabolic, ionic and electrical activities can be monitored from the surface of the brain. In the present study we included optical fibers for the monitoring of intracapillary hemoglobin oxygenation by use of the Erlangen Microlight Guide Spectrophotometer (EMPHO-I) from the surface of the gerbil brain. The newly developed MPA provides simultaneous information about oxygen delivery (oxydeoxy Hb), tissue pO2 level, as well as the intracellular oxygen balance (intramitochondrial redox state). The ionic homeostasis was evaluated by monitoring extracellular K+ and Ca2+ activities reflecting the permeability changes of cation channels as well as the activities of Na+,K(+)-ATPase and other ion linked transport processes. The electrical activities were monitored by a bipolar electrocortical surface probe and DC steady potential. The subjects of the present study were Mongolian gerbils (Meriones unguiculatus) anesthetized and operated according to our routine techniques. After 30 min of recovery from the operation each gerbil was exposed to a short anoxia, graded hypoxia, ischemia as well as spreading depression. The results can be summarized as follows: 1. A clear correlation was recorded between the changes in oxydeoxy Hb spectra, tissue pO2 level and oxidation-reduction state of intramitochondrial NADH under oxygen deficiency situations (hypoxia, ischemia). 2. Blood volume changes under various perturbations monitored by various probes (366 reflectance and EMPHO-I) correlated very well with each other. 3. The degree of inhibition of Na+,K(+)-ATPase induced by oxygen deficiency could be interpreted by changes in extracellular levels of K+ measured by the surface mini-electrode. 4. Brain stimulation induced by spreading depression mechanism led to transient changes in ionic homeostasis and increase in energy requirements. The major HbO2 response was an increase in oxygenation due to the large CBF increase as monitored by the laser Doppler flowmeter. 5. Changes in oxy-deoxy Hb under fast scanning of 500-600 nm during 2-3 seconds of bilateral carotid arterial occlusion provided an indirect index for tissue O2 consumption.
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PMID:Multiparametric evaluation of brain functions in the Mongolian gerbil in vivo. 133 23

Focal brain ischemia was produced in halothane-anesthetized Mongolian gerbils by occluding the right common and the left external carotid artery. Ninety minutes after vascular occlusion the following regional hemodynamic and metabolic parameters were evaluated in adjacent cryostat sections taken from seven different coronal planes of each brain: cerebral blood flow (CBF), glucose utilization (CMRG), and the tissue content of ATP and glucose. NADH fluorescence was recorded from the surface of the cryostat block. In addition, tissue slices were taken from each brain to determine the rate of phosphorylation of 2-deoxyglucose in ischemic and nonischemic regions. Depending on the density of ischemia, the following metabolic disturbances were observed. At CBF values below 35 ml x 100 g-1 x min-1 CMRG increased and at values below 25 ml x 100 g-1 x min-1 it declined sharply. Glucose content declined when CBF was below 35 ml x 100 g-1 x min-1 and ATP fell at CBF below 20 ml x 100 g-1 x min-1. At 10 ml x 100 g-1 x min-1 ATP was completely depleted. NADH fluorescence was found elevated at flow rates that caused an increase of glucose utilization and was maximal when CBF stopped. The ischemic thresholds for the initial increase in CMRG and the complete depletion of ATP content represent the metabolic equivalent of the penumbra zone and provide a basis for the evaluation of therapeutic procedures for the treatment of stroke.
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PMID:Threshold relationship between cerebral blood flow, glucose utilization, and energy metabolites during development of stroke in gerbils. 139 69

A prototype laser-fiber optic based sensor for in situ monitoring of nicotinamide adenine dinucleotide (NADH) has been developed. This system is based on a compact neodymium-yttrium-aluminum-garnet (Nd:YAG) laser with associated harmonic generators. Light distribution to and from tissue is handled by a fiber optic network, including a long optical fiber to be inserted into the target tissue. Immobilizing the enzyme lactate dehydrogenase on the fiber tip converts the monitoring channel into a lactate sensor. A new dual beam reflection approach for blood volume artifact compensation is tested. Detection sensitivity of free NADH in the micromolar region is achieved. The method and system configuration appear feasible for continuous in situ monitoring of two important indices of ischemia and hypoxia in a clinical setting.
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PMID:Tissue viability measurement by in situ fluorometry. 145 92

A unique blood supply to the brain, the 'Circle of Willis' (COW), exists in all mammals except for the Mongolian gerbil (Meriones unguiculatus). This system is capable of compensating for a decrease in blood supply in one of the four arteries, which may occur during pathological conditions. The posterior connection between the basilar artery and the carotid artery system have been found to be missing in most gerbils. Furthermore, in some of the animals, the anterior communication was not complete, thus leading to partial ischemia following unilateral carotid artery occlusion. Due to those peculiar characteristics, the Mongolian gerbil today has become a widespread animal model for cerebral ischemia studies. M. unguiculatus has been used in most of the studies while the level of ischemia has been evaluated by the development of neurological symptoms created by the occlusion of the carotid arteries. In the present study we investigated the vasculature structure of the commonly used gerbil, M. unguiculatus (MU-TF) and compared it to the vasculature of the Israeli gerbil, Meriones tristrami as well as to that of the Albino rat. We determined the correlation between the anatomical pattern and the biochemical responses during partial or complete ischemia and anoxia by monitoring the oxidation-reduction state of the intramitochondrial NADH using an in vivo surface fluorescence technique. The corrected fluorescence signal was found to be inversely correlated with oxygen availability and could thus be used as an indicator for the level of ischemia developed after carotid artery occlusion. This is the first time that the brain vasculature of two lines of M. tristrami (MT-HU, MT-BD) has been investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brain vasculature and mitochondrial responses to ischemia in gerbils. I. Basic anatomical patterns and biochemical correlates. 148 85

The correlation between the anatomy of brain vasculature and the metabolic responses to ischemia was studied in two strains of the Mongolian gerbil as compared to the albino rat. Gerbils belonging to the Meriones unguiculatus obtained from Tumblebrook Farms and from the NY Institute for Basic Research were compared to two lines of the Meriones tristrami obtained from two different breeders in Israel. In all groups of gerbils and in the albino rats, a significant correlation was found between the anatomical patterns of the Circle of Willis and the metabolic responses to ischemia as evaluated by NADH redox state measurements, namely, that with a complete anterior anatomical Circle of Willis the metabolic response to unilateral occlusion was minimal. In the anterior part of the Circle of Willis the various groups of gerbils exhibited the entire range of ischemia levels, from 0-100%, depending upon the anatomical structure of the arteries. In M. tristrami, the anterior communications between the two hemispheres were very well developed as compared to the various degrees of connection found in the different individuals of M. unguiculatus. This anatomical pattern corresponds well to the metabolic response recorded under unilateral and bilateral occlusion. The best connection in the posterior part, was found in M. tristrami. This was less frequent (10-20% of the gerbils) in M. unguiculatus. A clear correlation was found between the size of the posterior communicating artery and the changes in NADH redox state measured during bilateral carotid artery ligation. The variation between gerbils of the same litter was significantly smaller than that of the general population of the same strain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brain vasculature and mitochondrial responses to ischemia in gerbils. II. Strain differences and statistical evaluation. 148 86

Current forms of brain monitoring, such as electroencephalography (EEG), have had limited clinical utility. The EEG records spontaneous cerebrocortical activity and thus is an indirect indicator of metabolic demand and, to a lesser extent, an indicator of mismatch of supply versus demand. Ischemia modulates EEG activity in ways that can usually be detected, but EEG patterns can be similarly modulated by many other factors, including temperature and pharmacologic manipulation. This in vivo study in physiologically monitored animals evaluated the use of correlated optical spectroscopy, performed with an instrument having a fiberoptic light-guide bundle in contact with the cerebral cortex, for the simultaneous monitoring of cerebrovascular oxygen availability and intracellular oxygen delivery. A highly specific monitor of cerebral intracellular oxygen supply, the cerebrocortical intramitochondrial NADH redox state, was monitored in vivo with a fluorescence technique. Absorption spectroscopy was used concurrently to monitor hemoglobin content (blood volume) and oxygen saturation in the microcirculation. Correlated changes in optical signals from cerebrocortical NADH and hemoglobin were studied in a swine model (n = 7) of nitrogen hypoxia. Measurements were made at four wavelengths with a time-division, multiplexed fluorometer/reflectometer. Because the NADH fluorescence signal at 450 nm is affected by local changes in blood volume, a "corrected" fluorescence signal is usually calculated. In previous studies, where only two wave lengths have been measured, attempts at correction were based on reflectance at the excitation wavelength (366 nm). We compared estimators of changes in microcirculatory blood volume using reflection at two wavelengths: 366 nm and 585 nm, the wavelengths for maximum and isobestic absorption. The results of the studies were as follows: (1) during transient hypoxia, NADH and local hemoglobin saturation signals changed in concert with arterial pulse oximetry, with changes in NADH lagging behind changes in saturation by an average of 5.3 seconds; (2) after hypocapnic ventilation to a mean PaCO2 of 20.2 +/- 0.8 mm Hg, NADH increased by 11.5 +/- 8.7% (as compared with maximal change during anoxia), local hemoglobin saturation decreased by 7.7 +/- 6.4%, and local blood volume decreased by 12.5 +/- 13%, while arterial SpO2 was unchanged; (3) our two measures of local blood volume were closely correlated during carbon dioxide perturbations, but poorly correlated during hypoxic perturbation; and (4) NADH fluorescence provided a more rapid, sensitive indicator of oxygen deprivation than did the EEG. During transient hypoxia, EEG changes occurred 57.4 +/- 10.4 seconds after the onset of decline in local hemoglobin saturation, after NADH had completed 50% of its maximal increase.
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PMID:Correlated, simultaneous, multiple-wavelength optical monitoring in vivo of localized cerebrocortical NADH and brain microvessel hemoglobin oxygen saturation. 149 28

Using NADH fluorometry to monitor myocardial metabolism, the mechanism of reperfusion injury was investigated after the delivery of an experimental reperfusate. Using an isolated working heart preparation, rat hearts underwent 15 min of global ischemia at 37 degrees C. Following the ischemic insult, an oxygenated enriched reperfusion solution was given for 5 min. The hearts were then returned to a working state and aortic flow recorded to evaluate recovery. NADH levels were monitored throughout the experiment with a fluorometer and glycogen, AMP, ADP, and ATP were measured biochemically pre- and postischemia, after reperfusion and after recovery. In this study, reperfusion injury was best abated by an enriched reperfusate. Our results indicate the mechanism for this amelioration is not high-energy phosphate replenishment. Rather, as indicated by NADH fluorescence, the hearts attain an intermediate level of metabolism that permits glycogen to be restored and functional recovery to be improved.
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PMID:Monitoring myocardial reperfusion injury with NADH fluorometry. 161 62

1. Nilvadipine (FK 235, FR 34235) suppressed ischemia (20 min)-reflow (20 min)-induced paw edema of mice (ED30:0.4 mg/kg i.v. and 2 mg/kg p.o.). Other calcium entry blockers of dihydropyridine-type also suppressed the edema, but 30-fold higher doses were required. 2. Oral dosing of nilvadipine suppressed carrageenan-induced paw edema (ED30:15 mg/kg in rats and 20 mg/kg in mice) at a potency corresponding to that of an anti-inflammatory drug, ibuprofen. Nifedipine, nicardipine and nimodipine resulted in a suppression of 30% only with 100 mg/kg oral dosing in rats. Nitrendipine, diltiazem and verapamil were without effect. 3. Nilvadipine inhibited superoxide radical (O-2production from xanthine oxidase (XOD) both with lactate dehydrogenase + NADH method and cytochrome c method (IC50:90 and 100 micrograms/ml, respectively). Nifedipine and nicardipine showed some inhibition, but the other calcium entry blockers failed to inhibit significantly even at 320 micrograms/ml. As uric acid formation was not reduced by the tested drugs, the inhibitory action might be due to their O-2scavenging effects. 4. Superoxide production of neutrophils from casein-induced peritoneal fluid in rats was most strongly inhibited by nilvadipine when the cells were stimulated by a calcium ionophore, A23187 (IC50:4 micrograms/ml). Inhibition by this drug when stimulated by f-methonyl-leucyl-phenylalanine and phorbol myristate acetate was less effective (IC50:20 and 30 micrograms/ml, respectively). Nifedipine and nicardipine inhibited neutrophil O-2production at higher concentrations (30-200 micrograms/ml) with all stimulants. Inhibitory actions by other drugs were weak. 5. Triggering of atherosclerosis depends largely on the oxidative stress on blood vessels after recently established concept.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition by nilvadipine of ischemic and carrageenan paw edema as well as of superoxide radical production from neutrophils and xanthine oxidase. 165 7

Low-temperature electron paramagnetic resonance (EPR) spectroscopy and spin traps were used to measure paramagnetic species generation in rat hearts and isolated mitochondria. The hearts were freeze-clamped at 77 K during control perfusion by the Langendorff procedure, after 20-30 min of normothermic ischemia or 10-30 s of reperfusion with oxygenated perfusate. All EPR spectra measured at 4.5-50 K exhibited signals of both mitochondrial free radical centers and FeS proteins. The analysis of spectral parameters measured at 243 K showed that free radicals in heart tissue were semiquinones of coenzyme Q10 and flavins. The appearance of a typical "doublet" signal at g = 1.99 in low-temperature spectra indicated that a part of ubisemiquinones formed a complex with a high potential FeS protein of succinate dehydrogenase. Ischemia decreased the free radical species in myocardium approximately 50%; the initiation of reflow of perfusate resulted in quick increase of the EPR signal. Mitochondria isolated from hearts during control perfusion and after 20-30 min of ischemia were able to produce superoxide radicals in both the NADH-coenzyme Q10 reductase and the bc1 segments of the respiratory chain. The rate of oxyradical generation was significantly higher in mitochondria isolated from ischemic heart.
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PMID:Free radical metabolites in myocardium during ischemia and reperfusion. 165 95


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