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Biomedical subjects

A Mayevsky

Publications and source records attributed to A Mayevsky.

At least 37 records · Page 2Linked to original sources
PubMed1999

Brain metabolic and ionic responses to systemic hypoxia in the newborn dog in vivo.

Newborns are less sensitive than adults to hypoxic/ischemic injury. However, research into the mechanism of the newborn's relative resistance to reduced brain oxygen levels is relatively scarce, and the time-scale for the disappearance of resistance is not known. The multiprobe assembly (MPA) has enabled us to examine the resistance of puppies at various ages to hypoxia via continuous, simultaneous, on-line measurement of various ionic, metabolic and electrical parameters from the cerebral cortex. The parameters measured included electrocorticogram (ECoG), direct current (DC) steady state potential, extracellular potassium (Ke+) and calcium ion concentrations and intra-mitochondrial Nicotine amide adenine dinucleotide NADH redox levels. These parameters were measured under various degrees of hypoxia (fraction of inspiration oxygen was between 0-10%) in 6-h-old to 24-week-old puppies (n = 44). Sensitivity to hypoxia increased with age, being expressed in the leakage of potassium ions out of the cells (0.3 +/- 0.07 mM in the younger puppies and 3.0 +/- 1.3 mM in the older puppies) following an increase in intra-mitochondrial NADH redox levels. Potassium ion (Ke+) leakage was apparently due to depleted energy stores resulting from an impairment in the balance between oxygen supply and demand. Although the overall effect was similar, the kinetics of these changes were much faster in the older puppies. The time to initial increase of extracellular K+ was 2.5 +/- 0.1 min in the younger puppies and 0.9 +/- 0.1 min in the older puppies. The time to maximum increase of NADH was 3.2 +/- 0.2 min in the younger puppies and 1.4 +/- 0.1 min in the older puppies. Our results indicate that the older puppies utilize the existing oxygen faster than the younger puppies. It is concluded that the increased resistance of newborn puppies to hypoxia is due to intrinsic properties of the brain itself, like the ability of the membrane to maintain ionic homeostasis.

Age Factors↗
PubMed1999

Physiologic and biochemical monitoring during hyperbaric oxygenation: a review.

Hyperbaric oxygenation (HBO2) is an important treatment given to various groups of patients exposed to pathologic situations (i.e., carbon monoxide exposure). Since many hyperbaric patients are critically ill and are being treated for life-threatening disorders, it is necessary to monitor various physiologic and biochemical parameters. This is a review of 193 publications covering a wide range of monitored parameters representing metabolic, hemodynamic, respiratory, electrical, and biochemical activities. The significance of monitoring the physiologic, medical, and specific oxygen toxicity effects during HBO2 exposure (MHBO2) is described and emphasized. Further development of new monitoring devices and technologies will enable the improvement of patient management during HBO2 treatment given under various medical conditions. This review also presents new ideas about possible future monitoring of brain function under HBO2 conditions in experimental animals as well as under clinical conditions.

Animals↗
PubMed1998

Responses of rat brain to induced spreading depression following exposure to carbon monoxide.

Until recently carbon monoxide (CO) was known only for its noxious effects. Exposure to CO results in an autoregulatory increase in cerebral blood flow (CBF). Little information is available on brain energy metabolism under low CO concentrations and on the effect of CO on the stimulated brain. In this study cortical spreading depression (SD) was induced in order to cause transient brain depolarization and increased energy demand. The multisite assembly (MSA), which contains four bundles of optical fibers for monitoring the intramitochondrial NADH redox state and tissue reflectance as well as four DC electrodes enabling measurement from four consecutive points on the cerebral cortex, was used to measure energy metabolism and the propagation of SD waves during exposure to CO. CBF in the contralateral hemisphere was measured using the laser Doppler technique. Three experimental groups of animals were examined: SD was induced during exposure to 1000 ppm CO, immediately after exposure to CO and 90 min after cessation of exposure to CO. Three control groups were also examined, in which the animals underwent the same procedures but were not exposed to CO. In all animals exposure to CO was followed by a significant increase in CBF. The greatest effect was found when SD was induced immediately after cessation of exposure to CO. SD wave frequency decreased when induced immediately after exposure to CO, whereas it increased when SD was induced 90 min after exposure. The amplitude of the NADH oxidation waves and their integral were smaller during SD induced immediately after exposure to CO. The DC potential did not change, suggesting that CO did not affect the SD initiation mechanism but rather resulted in energy depletion during recovery from SD. This study demonstrates that even at a concentration of 1000 ppm CO interferes with the metabolic activity of the brain during repolarization of the SD-induced negativity.

Animals↗
PubMed1998

Thiopental induced cerebral protection during ischemia in gerbils.

Temporary interruption or reduction of cerebral blood flow during cerebrovascular surgery may rapidly result in ischemia or cerebral infarction. Thiopental has been shown to have cerebroprotective effects. However, the cerebroprotective dose of thiopental causes burst suppression of the EEG, thus this parameter cannot be used continuously for the detection of metabolic changes in the brain during thiopental anaesthesia. This study was performed in order to examine whether the multiparametric assembly (MPA), which measures energy metabolism CBF and mitochondrial (NADH) as well as extracellular ion concentrations (K+), can shed light on the mechanism of the cerebroprotective effects of thiopental. The MPA was placed on the brain of Mongolian gerbils and burst suppression of the ECoG was induced by thiopental. Cerebral ischemia was induced by occlusion of carotid arteries after burst suppression. Burst suppression of the ECoG was accompanied by a significant decrease in cerebral blood flow. In animals that received thiopental prior to ischemia, NADH increased to a lesser degree and extracellular potassium ion concentration increased to a lesser degree than in the control animals, indicating that thiopental affords protection of the brain under ischemic conditions due to improved energy metabolism. This study also demonstrates that the MPA can monitor changes occurring in the cerebral cortex even after the ECoG can no longer be used. Those findings have a significant value in the development of a new clinical monitoring device.

Animals↗
PubMed1998

Real time monitoring of rat liver energy state during ischemia.

Hepatic failure is one of the major problems developed during the posttransplantation period. A possible cause of hepatic failure is the prolonged ischemia induced during the implantation procedure. Hepatic ischemia leads to a reduction in oxygen supply, ATP level decline, liver metabolism impairment, and finally organ failure. The purpose of this study was to estimate the functional state of the liver by monitoring liver blood flow and the mitochondrial NADH redox state simultaneously and continuously during in situ liver ischemia followed by reperfusion. Measurements were performed using the multiprobe developed in our laboratory consisting of fibers for the measurement of relative liver blood flow (laser Doppler flowmetry) and mitochondrial redox state (NADH fluorescence). The experimental procedure included the temporary interruption of blood flow to the liver using three types of ischemia, hepatic artery occlusion, portal vein occlusion, and simultaneous occlusion of hepatic artery and portal vein, followed by a reperfusion period. These preliminary experiments showed a significant decrease in liver blood flow, following the three types of liver ischemia, and a significant increase in NADH levels. The probe used in this study incorporates the advantage of monitoring NADH and liver blood flow simultaneously and continuously from the same area on the surface of the liver. Since each of these two parameters is not calibrated in absolute units, the simultaneous monitoring decreases possible artifacts. Also, it will allow us to determine of the coupling between tissue blood flow and oxidative phosphorylation. It is believed that the measurements of respiratory chain dysfunction might predict organ viability in clinical organ transplantation situations. Using this probe may also help to decrease the variability in liver blood flow monitoring since liver blood flow monitoring is supported simultaneously with the mitochondrial redox state, which supplies the information on liver metabolic and functional state.

Animals↗
PubMed1998

Real-time multiparametric monitoring of the injured human cerebral cortex--a new approach.

Intracranial pressure (ICP) is currently the main parameter monitored following severe head injury or during the post operative period in neurosurgical patients. The normal cerebral cortex depends upon a continuous supply of O2, and direct coupling exists between adequate cerebral blood flow (O2 supply) and ion homeostasis as well as electrical activities. We have developed a new "Brain Function Analyzer-BFA" which enabled monitoring of the following parameters continuously in real time from the surface of the cortex: ICP; tissue blood flow & volume; intramitochondrial NADH redox state; DC steady potential; electrocorticography; tissue temperature. The probes were assembled in a Brain Function Multiprobe (BFM) which was connected to the brain via the burr hole procedure used for ICP monitoring. Measurements were performed in 18 comatose patients after severe head injury (GCS < or = 8) who were monitored in the ICU for 48-72 hours. The basic concept of the multiparametric monitoring approach was proven to be practical in neurosurgical patients. Clear correlations were recorded between hemodynamic, metabolic, ionic and electrical activities under various treatments administered to the patients or after pathological events. Responses similar to cortical spreading depression and ischemic depolarization were recorded from a severely head injured patient.

Brain Injuries↗
PubMed1998

Effect of hyperbaric oxygen therapy on survival after global cerebral ischemia in rats.

BACKGROUND: Hyperbaric oxygenation (HBO) has been considered for many years for the treatment of severe brain ischemia. However, its efficacy has not been proven. The aim of this study was to shed light on this question. METHODS: Acute global cerebral ischemia was induced in 18 rats using the four-vessel occlusion model. Regional cerebral blood flow (CBF) was determined by laser-Doppler flowmetry using a flexible 1 mm fiberoptic probe. Two stainless steel screws were used to measure the spontaneous electrical activity from the contralateral hemisphere. After ischemia monitored by laser-Doppler flowmetry and ECoG, the animals were divided into two groups: (1) control animals that breathed air at atmospheric pressure and (2) rats exposed to HBO at three atmospheres absolute pressure (ATA) for 1 hour. Survival time and rate were recorded for both groups of animals for 14 days. RESULTS: The survival rate in the study group was significantly higher (45%) than in the control group (0%). In the animals that did not survive the 14-day period, those exposed to HBO survived longer than the control animals (59.8+/-9.1 hour versus 17.9+/-2.7 hours, p < 0.05). CONCLUSION: This investigation demonstrates that HBO administered after global cerebral ischemia can increase survival in a rat stroke model.

Animals↗
PubMed1998

Multiparametric monitoring of brain oxygen balance under experimental and clinical conditions.

In order to evaluate the relationship between brain oxygen supply and demand (O2 balance) in real time, it is necessary to use a multiparametric monitoring approach. Cerebral blood flow (CBF) is a representative parameter of O2 supply. The extracellular level of K+ is a reliable indicator of O2 demand since more than 60% of the energy consumed by the brain is utilized by active transport processes. Mitochondrial NADH redox state can represent the balance between O2 supply and demand. In order to monitor the brain of experimental animals or patients, we constructed the multiparametric assembly (MPA) and the following parameters were monitored simultaneously and in real time: CBF, CBV, NADH redox state, extracellular K+, DC potential, EEG, tissue temperature and ICP. Animals were exposed to hypoxia, ischemia, hypercapnia, hyperoxia and spreading depression (SD) and the relative changes in CBF and NADH were calculated and found to be significant indicators of brain energy state. Monitoring these two parameters increases the possibility of differentiating between various pathophysiological states. Each added parameter increases the power of diagnosis and determination of the functional state of the brain. Preliminary results obtained in patients monitored in the ICU or in the OR show that the responses to hypercapnia, spreading depression or ischemia are similar to those measured in experimental animals.

Brain↗
PubMed1997

Can the Indo-1 fluorescence approach measure brain intracellular calcium in vivo? A multiparametric study of cerebrocortical anoxia and ischemia.

Indo-1 fluorescence was used to monitor intracellular calcium levels in the cat brain in vivo, using the approach proposed by Uematsu et al. [Uematsu D., Greenberg J. H., Reivich M., Karp A. In vivo measurement of cytosolic free calcium during cerebral ischemia and reperfusion. Ann Neurol 1988; 24: 420-428]. In addition, extracellular calcium and potassium levels, NADH redox state, electrocorticogram (ECoG), DC potential and relative cerebral blood flow were monitored simultaneously. Changes in the Indo-1 fluorescence ratio F400/F506 were monitored during anoxia, reversible ischemia and irreversible ischemia. Although these perturbations resulted in the expected changes in extracellular calcium and potassium levels, NADH redox state, ECoG and other physiological parameters, they did not result in significant increases in the F400/F506 ratio. The apparent insensitivity of the in vivo Indo-1 approach is due to the difficulty in obtaining accurate fluorescence signals from Indo-1 in the brain. Two reasons for this difficulty appear to be problems in loading Indo-1 into the brain, and problems in correcting Indo-1 fluorescence signals for changes in NADH fluorescence and changes in absorption of intrinsic chromophores. Under the conditions of our in vivo cat experiments, Indo-1 fluorescence is not a viable approach for measuring changes in cerebral intracellular calcium levels.

Animals↗
PubMed1996

Cortical spreading depression recorded from the human brain using a multiparametric monitoring system.

The number of parameters (i.e., EEG or ICP-intracranial pressure) routinely monitored under clinical situations is limited. The brain function analyzer described in this paper enables simultaneous, continuous on-line monitoring of cerebral blood flow (CBF) and volume (CBV), intramitochondrial NADH redox state, extracellular K+ concentrations, DC potential, electrocorticography and ICP from the cerebral cortex. Brain function of 14 patients with severe head injury (GCS < or = 8), who were hospitalized in the neurosurgical or general intensive care unit was monitored using this analyzer. Leao cortical spreading depression (SD) has been reported in many experimental animals but not in the human cerebral cortex. In one of the patients monitored, spreading depression was observed. This is the first time that spontaneous repetitive cortical SD cycles have been recorded from the cerebral cortex of a patient suffering from severe head injury. Typical SD cycles appeared 4-5 h after the beginning of monitoring this patient. During the first 3-4 cycles the responses of this patient were very similar to the responses to SD recorded in normoxic experimental animals. Electrocorticography was depressed whereas extracellular K+ levels increased. The metabolic response to spreading depression was characterized by oxidation of intramitochondrial NADH concomitant to a large increase in CBF. During brain death, an ischemic depolarization, characterized by decrease in CBF and an irreversible increase in extracellular K+, was recorded.

Brain↗
PubMed1996

Effects of carbon monoxide on the brain may be mediated by nitric oxide.

Carbon monoxide (CO) is known to be a toxic molecule due to the high affinity of hemoglobin for it. However, it has recently been shown that low doses of CO may play a physiological role. The aim of the present study was to examine processes occurring in the brain during exposure to 1,000 parts per million CO that result in an increase in cerebral blood flow (CBF) but are not accompanied by changes in oxidation metabolism. This study was carried out in awake rats with the multiprobe assembly developed in this laboratory for the simultaneous continuous measurement of CBF, intramitochondrial NADH redox levels, direct current potential, and extracellular concentrations of K+, Ca2+, and H+ as well as the electrocorticogram. Exposure to 1,000 parts per million CO in air resulted in an increased CBF without any concomitant changes in any of the other metabolic or ionic parameters measured. This indicates that tissue hypoxia was not the trigger for this vasodilation. Injection of N omega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, before exposure to CO effectively blocked the increase in CBF that was observed when the animal was exposed to CO without prior injection of L-NNA. Furthermore, electrocorticographic depression was observed after the combined treatment of L-NNA and CO. In conclusion, exposure to relatively low doses of CO apparently does not have a deleterious effect on oxidative metabolism because the increase in CBF after this exposure is sufficient to prevent changes in oxidative metabolism, as indicated by the fact that NADH levels remained constant. This protective autoregulatory effect may be mediated by nitric oxide.

Animals↗
PubMed1996

Continuous multiparametric monitoring of brain activities following fluid-percussion injury in rats: preliminary results.

Severe head injury can result in a high mortality rate or irreversible brain damage. One technique used to induce traumatic brain injury (TBI) is exposure of the brain to fluid percussion pressure while monitoring the increase in intracranial pressure (ICP). Since brain injury is a multifactorial, pathological, time-dependent state, the multiparametric monitoring approach was adopted for studying fluid percussion effects on the rat brain. A multiprobe assembly (MPA) connected to the brain in vivo (right hemisphere) enabled the simultaneous monitoring of CBF, NADH redox state, extracellular K+, Ca2+, H+ levels as well as DC potential, ECoG and ICP. The animal was connected to the monitoring system and exposed to TBI after a recuperation period of at least 3 hours after the end of the operation. Two typical responses to TBI were recorded in our preliminary experiments. When severe injury was induced, ischemic depolarization (ID) developed, whereas mild or moderate injury led to repetitive spreading depression (SD) cycles. The relationship between the ID and SD observed under TBI is important to the understanding of the mechanism of brain injury. ICP before injury was between 2-6 mm Hg and increased to 20-22 mm Hg 2-3 minutes after the ID. After severe head injury, ICP remained high and in some cases increased to critical values causing death of these animals. Some animals developed seizures at various stages after the TBI. Hyperbaric oxygenation was used as a therapeutic tool to treat severely injured animals. These preliminary results suggest that it is feasible and practical to use the MPA approach for monitoring the brain after TBI.

Brain Injuries↗
PubMed1996

Multiparameter monitoring and analysis of in vivo ischemic and hypoxic heart.

We describe a unique in vivo technique which addresses the multifactorial function of the heart, i.e., simultaneous measurement of myocardial ion transport (two mini-electrode systems to measure K+e and Ca2+e), energy metabolism (NADH fluorescence to measure NADH redox state), and coronary flow (laser-Doppler perfusion) using a multiprobe assembly (MPA) which contains transducers for all measurements. The MPA (which is 6 mm in diameter) was applied to the external surface of the heart in an open chest dog model. To test MPA function, myocardial ischemia was produced by application of a balloon occluder to the left anterior descending coronary (LAD) artery, and hypoxia was produced by changing the inspired O2-N2 ratio until the PaO2 was 20-30 torr. The MPA simultaneously monitored changes in ion flux, heart metabolism, and tissue perfusion during pathophysiological intervention.

Animals↗
PubMed1995

Multiparametric monitoring of the awake brain exposed to carbon monoxide.

We have applied in vivo real-time techniques to monitor the physiological changes associated with exposure to a pattern of carbon monoxide (CO) known to cause brain oxidative stress. Using a multiparametric monitoring device connected to the brain, we exposed unanesthetized rats to two levels of CO, 0.1 and 0.3% in air. Energy metabolism was evaluated by the optical monitoring of relative cerebral blood flow (CBF) and intramitochondrial redox state. Ionic homeostasis was assessed by measurements of K+,Ca2+, and H+ or Na+ levels in the extracellular space. The electrical parameters monitored were the electrocorticogram and direct current steady potential. Under 1,000 ppm of CO, the CBF was increased significantly without any measurable change in the NADH redox state, suggesting that the cause for the increased CBF was not hypoxia. Exposing the awake rat to 1,000 ppm of CO (40 min) followed by 3,000 ppm of CO (20 min) led to an increase in CBF followed by episodes of spontaneous brain depolarizations characterized by changes in ionic homeostasis and blood flow. These changes were similar to those recorded under cortical spreading depression. In most animals exposed to 3,000 ppm of CO, spontaneous oscillations in CBF and NADH redox state that were negatively correlated were recorded. The results indicate that an inspired CO level of 0.1% had effects largely restricted to blood flow, whereas at a higher CO level an additional impairment in energy supply resulted in a complex pattern of effects similar to that caused by brain ischemia.

Animals↗
PubMed1992

Brain vasculature and mitochondrial responses to ischemia in gerbils. I. Basic anatomical patterns and biochemical correlates.

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)

Animals↗
PubMed1992

Brain vasculature and mitochondrial responses to ischemia in gerbils. II. Strain differences and statistical evaluation.

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)

Animals↗