Cerebral blood flow and brain mitochondrial redox state responses to various perturbations in gerbils.
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Animals↗
Biomedical subjects
A Mayevsky
Publications and source records attributed to A Mayevsky.
Correlated, simultaneous, multiple-wavelength optical monitoring in vivo of localized cerebrocortical NADH and brain microvessel hemoglobin oxygen saturation.
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.
Animals↗
Sperm motility index: a new parameter for human sperm evaluation.
OBJECTIVE: The study was performed to evaluate the correlation between sperm motility index, a novel parameter of semen quality, and routine semen analysis parameters by microscopic evaluation. DESIGN: Sperm motility index was measured by an electro-optical device, the Sperm Quality Analyzer (United Medical Systems Inc., Santa Ana, CA). Human semen samples covering the whole span of qualities were analyzed prospectively and simultaneously by both methods. SETTING: Samples were collected from patients referred to university hospital infertility clinics. PATIENTS, PARTICIPANTS: Nine hundred sixty-eight semen samples of 812 patients and healthy men were analyzed. MAIN OUTCOME MEASURE(S): Sperm motility index is a measurement of optical density fluctuations caused by motile cells; therefore, a positive correlation was anticipated between its values and semen motility parameters. RESULTS: Sperm motility index values demonstrated statistically significant correlation with motile cell concentration, total cell concentration, and percent motile cells. They were also shown to reliably represent semen quality assessment obtained by two experienced andrologists. CONCLUSIONS: The sperm motility index provides a reliable and objective reflection of semen motility parameters and quality.
Autoanalysis↗
Cerebral blood flow and oxygen consumption in cortical spreading depression.
We determined the effects of spreading depression on local cerebral O2 supply, oxygenation, and O2 consumption in the anesthetized rat. Spreading depression was induced by application of 0.5 M KCl to the frontal cortex. Regional cerebral blood flow was determined with [14C]iodoantipyrine and regional O2 extraction was determined microspectrophotometrically. The passage of the spreading depression wave was determined with a multiprobe assembly that recorded NADH redox state (surface fluorometry), extracellular K+ activity, and DC steady potential (surface minielectrodes). As the wave of spreading depression passed, there was an increase in extracellular K+ and a decrease in NADH. Cerebral blood flow was significantly increased (120 +/- 51 ml/min/100 g, mean +/- SD) during the wave as compared with other regions. In the affected cortex, blood flow was not different from that in the contralateral cortex (69 +/- 28 ml/min/100 g) either before or after the wave of spreading depression passed. Arterial and venous O2 saturation were unaffected by the wave and the histogram of O2 saturations of examined veins followed a similar normal distribution in all regions. Oxygen extraction was not altered by the wave of spreading depression. Oxygen consumption was significantly increased during the wave to 7.4 +/- 3.7 ml O2/min/100 g compared with the contralateral cortex (5.1 +/- 2.6 ml/min/100 g) and other regions. It can be concluded that spreading depression caused an increase in cerebral O2 consumption that was adequately matched by an increase in local blood flow. Oxygen delivery was not limited during spreading depression and its effects were quickly over as evidenced by the lack of alteration in oxygenation after the wave of spreading depression passed.
Animals↗
Age dependence of steady state mitochondrial oxidative metabolism in the in vivo hypoxic dog brain.
Mitochondrial bioenergetics were investigated in newborn, neonatal and adult dog brains during normoxia and hypoxia. The ratio of the rate of ATP synthesis to the maximum synthesis rate (V/Vmax), phosphorylation potential, [ADP] and PCr/Pi, were used to evaluate age related mitochondrial hypoxic tolerance. These indicators were calculated from the phosphorus compounds measured by in vivo 31P MRS quantitatively using ATP as an internal reference. Indicators and substrates of mitochondrial function, V/Vmax, ADP, and Pi reached a peak value during the neonatal (3-21 days) period of development, suggesting that the oxidative metabolism of the neonate is more vulnerable to stress when compared to newborns and adults. Distinction among newborns and neonates became apparent during hypoxia. Newborns (0-2 days old) showed substantial tolerance by maintaining V/Vmax until exposure to severe hypoxia. Older neonates (3-21 days old) showed increases in V/Vmax, [Pi] and [ADP] under less than severe conditions of hypoxia. Adults exhibited low V/Vmax values even during exposure to severe hypoxia, further indicating that mitochondrial oxidative processes are more stable in adults than in newborns and neonates. This study provides evidence that newborns and adults are more capable of maintaining mitochondrial function under conditions of minimal to moderate hypoxia than 3-21 day old neonates.
Adenosine Triphosphate↗
Oscillations of cortical oxidative metabolism and microcirculation in the ischaemic brain.
A new in vivo model for studying brain metabolic and haemodynamic oscillatory phenomena during ischaemia is described. In this model acute or chronic occlusion of one or two carotid arteries in the rat is performed. Due to the partial ischaemia developed, oscillations in the level of intramitochondrial pyridine nucleotides (NADH) as well as flavoproteins (Fp) were recorded from the brain by monitoring the fluorescence of these respiratory chain components. The two fluorescent signals (NADH and Fp) were measured by using the time sharing or DC fluorometer/reflectometer. The changes in the reflected light at the excitation wavelengths (366 and 450 nm) were recorded simultaneously. Bilateral carotid artery occlusion induced immediate oscillations (6-9 waves per min) in the mitochondrial redox state as well as in tissue blood volume in both hemispheres. To verify the accuracy of the NADH monitoring system, including the correction technique for haemodynamic and other artifacts, we used the intracarotid artery saline bolus injection approach. The results could be summarized as follows: (1) unilateral carotid artery occlusion resulted in delayed development of oscillations, particularly in the ipsilateral hemisphere; (2) the oscillation phenomenon was reversible if recirculation restarted within 5 min. Occlusion for more than 30 min resulted in irreversible oscillations; (3) the oscillation appearances and intensities were affected by various physiological conditions. Vasoconstriction, induced by hyperoxia, stimulated the oscillations while vasodilation, induced by hypercapnia, depressed them. Anoxia, hypoxia and spreading depression (SD) abolished the oscillations. Glucose injection was not effective.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthetics↗
In vivo correlation of myocardial metabolism, perfusion, and mechanical function during increased cardiac work.
STUDY OBJECTIVE: The aim was to study the in vivo interaction and regulation of myocardial perfusion, metabolism, and pump function in an open chest canine model using a combination of potentially non-invasive and clinically useful techniques. DESIGN: To assess potential regulatory mechanisms and the interaction of myocardial perfusion, metabolism, and contractile function responses during changes in cardiac workload, noradrenaline (1 microgram.kg-1.min-1) was infused and hypoxia was produced by increasing the inspired ratio of nitrogen to oxygen to produce a PaO2 of 2.6-4.0 kPa in separate interventions. SUBJECTS: Nine mongrel dogs of either sex, age 2-5 years, weight 8.5(SD 2.2) kg, were studied in separate interventions. MEASUREMENTS AND MAIN RESULTS: Myocardial perfusion was determined using 2H nuclear magnetic resonance (NMR) measured washout of deuterium oxide from the left ventricle interpreted with a one component Kety-Schmidt exponential model. High energy phosphate bioenergetics were determined by 31P NMR measurements of the phosphocreatine/ATP ratio. Redox state was estimated by nicotinamide adenine dinucleotide fluorometry expressed as percent change from the baseline, normalised to maximum response measured at 100% inspired N2. Mechanical function was evaluated using heart rate X systolic blood pressure and oxygen consumption measurements. During both noradrenaline infusion and hypoxia, mechanical function increased significantly from control values: heart rate X systolic blood pressure = 1.9(SD 0.5), 3.6(0.1), and 2.6(0.4), respectively; oxygen consumption = 0.9(2), 1.6(0.1), and 1.2(0.6) ml.min-1.100 g-1. Myocardial perfusion increased to support the increased workloads, from 87(10) to 131(20), and from 60(12) to 182(14) ml.min-1.100 g-1, respectively. ADP, estimated by the phosphocreatine/ATP ratio, did not change during noradrenaline infusion [2.4(0.2) to 2.4(0.7)], but decreased during hypoxia [2.4(0.4) to 1.7(0.5)]. Redox state decreased during noradrenaline infusion, from 100% to 84(0.7)%, and increased during hypoxia, from 100% to 140(10)%. CONCLUSIONS: Similar changes in workload induced by different physiological stimuli are associated with different biochemical responses even though changes in perfusion are similar. The data suggest that myocardial function is regulated by different biochemical mechanisms under different physiological conditions, ie, there is probably no universal regulator of myocardial function. It is now possible to evaluate potential metabolic regulators of myocardial function in an in vivo animal model.
Animals↗
In vivo mechanisms of myocardial functional stability during physiological interventions.
Metabolic regulatory mechanisms are designed to maintain stable myocardial function during extremes in physiological insult; they can now be studied in vivo and may provide insight into mechanisms of altered myocardial functional decompensation during disease processes. To determine mechanisms of myocardial stability during hypoxia and acute pressure loading, creatine kinase (CK) kinetics (forward rate constant, Kf, and flux of phosphocreatine, PCr, to adenosine triphosphate, ATP), and nicotinamide adenine dinucleotide (NADH) redox state were determined with 31P nuclear magnetic resonance (NMR) and NADH fluorometry, respectively, and correlated with heart work (heart rate x systolic blood pressure, HR x SBP), cardiac output (CO) and O2 consumption (MVO2) in 15 anesthetized open chest dogs. Hypoxia (PaO2 of 30-35 mm Hg) was produced in 6 dogs with an inspired O2/N2 of 200/3,000. Cardiac loading was produced in 9 dogs by administration of norepinephrine (NE, 1 micrograms/kg/min). Each dog acted as its own control. Baseline NADH fluorometry, 31P-NMR saturation transfer and cardiac function measurements were performed simultaneously in each dog, after which the experimental interventions were made. Similar increases in HR x SBP, CO, and MVO2 which occurred during both interventions were associated with different bioenergetic responses. During NE infusion, the Kf of CK increased from control; during hypoxia, the Kf decreased from control (p less than 0.05). Flux of PCr----ATP was significantly lower during hypoxia than during NE infusion (p less than 0.05). PCr was decreased significantly during NE infusion (p less than 0.05). In addition, NADH redox state increased (from baseline of 100%) during hypoxia (140 +/- 10%) and decreased during NE infusion (78 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Level of ischemia and brain functions in the Mongolian gerbil in vivo.
The Mongolian gerbil (Meriones unguiculatus) provides a very useful animal model to study the effects of ischemia on brain functions. In this model it is possible to induce two levels of ischemia in the same animal. Thus, monitoring the brain in vivo in real-time will provide meaningful information regarding the development of ischemic injury as well as the follow-up during the recirculation period. The aims of the study were as follows: (1) To elucidate the mechanism behind the development of ischemic depolarization under unilateral and bilateral carotid artery occlusion. (2) To exclude the possibility that removal of the dura mater will affect the results. (3) To correlate the kinetics of the recovery processes to the level of ischemia. We tested the correlation between energy depletion level (evaluated by intramitochondrial NADH redox state) and the development of ischemic depolarization (ID) and vasospasm (evaluated by extracellular K+, DC potential and 366 nm reflectance changes, respectively) under partial and complete ischemia (induced by unilateral or bilateral carotid artery occlusion) using the multiparametric monitoring system (MPA). In 12 out of 32 gerbils monitored by the MPA, the dura mater remained intact, while in the other 20, it was removed very gently before connecting the MPA to the brain. Two types of responses to unilateral carotid artery occlusion were recorded and the gerbils were divided into groups according to the development of the ID. In a third group of 5 gerbils we tested the effect of 1-5 min of bilateral occlusion on the various parameters monitored.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Time resolved 3-dimensional recording of redox ratio during spreading depression in gerbil brain.
Optical fluorescence and reflectance measurements have been used to map the distribution of metabolic states in three dimensions in the gerbil brain with a spatial resolution of 200 microns an a time resolution of 4-6 s. In Mongolian gerbils anesthetized with pentobarbital, the redox states of the nicotinamide adenine dinucleotide (NADH) and flavoprotein components of the electron transport chain exhibit two distinct phases during the wave of spreading depression: (1) a transient period of oxidation and (2) a prolonged period of reduction, during which the cytochromes are reduced, and the hemoglobin is predominantly in the deoxy form. These data are interpreted as indicating that the energy demand placed on the gerbil brain during such spreading depression wave is sufficient to drive the brain temporarily hypoxic.
Animals↗
Oxygen supply and brain function in vivo: a multiparametric monitoring approach in the Mongolian gerbil.
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Animals↗
Brain ischemic depolarization and vasospasm in the Mongolian gerbil: the dependence on energy depletion levels.
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Animals↗
Brain mitochondrial redox state, tissue haemodynamic and extracellular ion responses to four-vessel occlusion and spreading depression in the rat.
Fibre-optic surface fluorometer reflectrometry was used to monitor the NADH (nicotine adenine dinucleotide) redox state from rat brain during three- or four-vessel occlusion. To compare the completeness of the electrocauterization of the vertebral arteries and the effectiveness of the anterior cerebral arteries, two light guides were implanted above the cerebral hemispheres. The NADH level was measured and correlated with the changes in the intensity of the reflected light at the excitation wavelength (366 nm) and to the ECoG (electrocorticogram). In the present study, we used ten rats in which unilateral and bilateral carotid occlusion were performed. In a second group of rats we tested the effects of four-vessel occlusion on the metabolic and extracellular K+ and Ca2+ activities as compared with those recorded under spreading depression conditions. These experiments were done by using the multiprobe assembly (MPA) approach. The results could be summarized as follows: (1) in the four-vessel occlusion model, the level of cerebral ischaemia could be estimated quantitatively, in real-time, by monitoring the NADH redox state; (2) unilateral carotid occlusion (after vertebral coagulation) led to a variable level of ipsilateral ischaemia, depending upon the blood flow compensation between the two hemispheres; (3) fibre-optic fluorometry enabled the correlation of NADH redox state with other physiological parameters as well as during after-brain ischaemia; (4) using the MPA in rats exposed to four-vessel occlusion as well as spreading depression, we identified the differences between the two pathological states, although there were some similarities in the ion homeostasis responses.
Animals↗
Cerebral energy metabolism and oxygen state during hypoxia in neonate and adult dogs.
The relationship between a noninvasive determination of relative oxygen saturation of Hb circulating in brain tissue (StO2) and energy metabolism was investigated with respect to age [dogs in three age groups (0 to 6-d-old, 7- to 21-d-old, and adults)] and to severity of brain hypoxia using double beam spectroscopy of Hb deoxygenation and nuclear magnetic resonance spectroscopy of energy metabolism. The in vivo oxy-Hb dissociation was determined from the relationship between StO2 curve in the adult dog brain and sagittal sinus oxygen partial pressure during graded hypoxemia and found to be sigmoidal with an oxygen dissociation constant of 26.6 mm Hg. This agreed with an in vitro determination for oxygen dissociation constant of 28.2 mm Hg in adult dog red cells. The arterial oxygen pressure at which brain StO2 was reduced by 50% was shifted toward the right with increasing age (22.2, 33.8, and 40.8 mm Hg, respectively). This correlated with an in vitro oxygen dissociation constant of red cell Hb of 17.0, 22.3, and 28.2 mm Hg in the three age groups, respectively. The phosphocreatine-inorganic phosphate ratio (PCr/Pi) was used to relate changes in cellular energy metabolism during hypoxia with changes in StO2. There was no change in PCr/Pi when StO2 had decreased to 50% of the control value. However, when the brain StO2 had decreased to between 7 and 15%, a reduction of PCr/Pi to 50% of the normoxic value occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Effects of nimodipine on the responses to cerebral ischemia in the Mongolian gerbil.
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Animals↗
Molecular mechanisms of gossypol action on sperm motility.
1. Gossypol acetic acid inhibits collective motility of ejaculated ram spermatozoa. 2. Oxygen consumption was stimulated at low gossypol concentrations and inhibited as the concentrations are increased. 3. Gossypol inhibits respiration of permeabilized spermatozoa supported by durohydroquinome, which indicates a direct inhibition of mitochondrial electron transport chain. 4. The rapid reduction of mitochondrial dependent motility, high uncoupling effect and almost complete inhibition of mitochondrial calcium accumulation, indicate that gossypol inhibits motility in a mechanism by which mitochondrial uncoupling is involved.
Animals↗
Fiber optic surface fluorometry/reflectometry and 31-p-NMR for monitoring the intracellular energy state in vivo.
Various members of the respiratory chain exhibit different optical properties in the reduced and oxidized forms, thus enabling the non-invasive monitoring of various organs in vitro as well as in vivo. Since the pioneering work of Chance, Cohen, Jobsis and Schoener in 1962, many groups of investigators adopted their approach in monitoring NADH oxidation reduction states in vivo for the brain as well as for other body organs. In 1972, we introduced flexible, optical fibers into the surface fluorometry replacing the usual "rigid" optical system used by other groups. During the last decade, this technique has been developed, improved and applied to many experimental setups in brain research and very recently was combined with 31P NMR spectroscopy for the puppy and the adult dog brain in vivo. In our system, the effects of movement artifacts and changes in blood oxygenation are negligible while the effects of tissue absorption or blood volume changes are considerable and could be minimized by subtraction of the reflectance signal from that of the fluorescence (1:1 ratio) providing the corrected fluorescence signal.
Anaerobiosis↗
Brain oxidative metabolism of the newborn dog: correlation between 31P NMR spectroscopy and pyridine nucleotide redox state.
The effects of both anoxia and short- and long-term hypoxia on brain oxidative metabolism were studied in newborn dogs. Oxidative metabolism was evaluated by two independent measures: in vivo continuous monitoring of mitochondrial NADH redox state and energy stores as calculated from the phosphocreatine (PCr)/Pi levels measured by 31P nuclear magnetic resonance (NMR) spectroscopy. The hemodynamic response to low oxygen supply was further evaluated by measuring the changes in the reflected light intensity at 366 nm (the excitation wavelength for NADH). The animal underwent surgery and was prepared for monitoring of the two signals (NADH and PCr/Pi). It was then placed inside a Phosphoenergetics 260-80 NMR spectrometer magnet with a 31-cm bore. Each animal (1-21 days old) was exposed to short-term anoxia or hypoxia as well as to long-term hypoxia (1-2 h). The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Pi was greater than 1 (1.2-1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the FiO2 levels was recorded. (b) A clear correlation was found between the decrease in PCr/Pi values and the increased NADH redox state developed under decreased O2 supply to the brain. (c) Exposing the animal to moderately long-term hypoxia led to a stabilized low-energy state of the brain with a good recovery after rebreathing normal air. (d) Under long-term and severe hypoxia, the microcirculatory autoregulatory mechanism was damaged and massive vasoconstriction was optically recorded simultaneously with a significant decrease in PCr/Pi values.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗