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Biomedical subjects

G A Gregory

Publications and source records attributed to G A Gregory.

At least 37 records · Page 2Linked to original sources
PubMed1993

Fructose-1,6-bisphosphate reduces infarct volume after reversible middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: We tested the hypothesis that fructose-1,6-bisphosphate, when administered 10 minutes before the end of 2 hours of reversible middle cerebral artery occlusion, reduces ischemia-reperfusion injury and infarct volume measured after a 3-day survival period in rats. METHODS: After 1 hour and 50 minutes of middle cerebral artery occlusion by the intraluminal suture method, fructose-1,6-bisphosphate, 500 mg/kg in group 1 and 350 mg/kg in group 2 (or an equivalent volume of 1.8% saline as placebo in each group), was given intravenously for a period of 15 minutes to fasted adult Sprague-Dawley rats. After 2 hours of ischemia, the suture was withdrawn and the rats allowed to survive for 3 days. The areas of infarction in 10 hematoxylin-eosin-stained coronal sections of the brain were measured and used to calculate infarct volume. RESULTS: In group 1, fructose-1,6-bisphosphate decreased total cerebral hemispheric infarct volume by 43% (from 199.6 +/- 11.2 to 114.2 +/- 35.8 mm3, P < .04; mean +/- SEM). Cerebral cortical and subcortical infarct volumes were decreased by 46% (from 137.3 +/- 7.5 to 74.1 +/- 28.6 mm3, P < .04) and 36% (from 62.3 +/- 5.1 to 40.0 +/- 8.3 mm3, P < .04), respectively. In group 2, fructose-1,6-bisphosphate had no effect on infarct volume in rats that developed mild intraischemic hyperthermia, but in rats kept normothermic during ischemia, fructose-1,6-bisphosphate reduced subcortical infarct volume from 53.7 +/- 8.1 to 18.4 +/- 8.0 mm3 (P < .03). CONCLUSIONS: Fructose-1,6-bisphosphate improves functional neurological outcome and reduces infarct volume after reversible middle cerebral artery occlusion in rats.

Animals↗
PubMed1993

Modification of hypoxia-induced injury in cultured rat astrocytes by high levels of glucose.

BACKGROUND AND PURPOSE: Preexisting hyperglycemia exacerbates central nervous system injury after transient global and focal cerebral ischemia. Increased anaerobic metabolism with resultant lactic acidosis has been shown to cause the hyperglycemic, neuronal injury. The contribution of astrocytes in producing lactic acidosis under hyperglycemic/ischemic conditions is unclear, whereas the protective role of astrocytes in ischemic-induced neuronal injury has been documented. The ability of astrocytes to maintain energy status and ion homeostasis under hyperglycemic conditions could ultimately reduce neuronal injury. Therefore, we determined the effects of increased glucose concentrations on glucose utilization, lactate production, extracellular pH, and adenosine triphosphate concentrations in hypoxia-treated astrocyte cultures. METHODS: Primary astrocytes were prepared from neonatal rat cerebral cortices. After 35 days in vitro, cultures were incubated with 0-60 mmol/L glucose and subjected to hypoxic conditions at 95% N2/5% CO2 for 24 hours. In addition, under high-glucose conditions (30 mmol/L), astrocytes were exposed to up to 72 hours of hypoxia. Determination of lactate dehydrogenase efflux, adenosine triphosphate concentrations, and extracellular lactate concentrations defined astrocyte status. Equiosmolar levels of mannitol were added in place of high glucose concentrations to distinguish hyperosmotic effect. RESULTS: When physiological concentrations of glucose (7.5 mmol/L) or lower concentrations were used, significant cell damage occurred with 24 hours of hypoxia, as determined by increased efflux of lactate dehydrogenase and loss of cell protein. When higher glucose concentrations (15-60 mmol/L) were used, efflux of lactate dehydrogenase was similar to that observed in normoxic cultures, despite an increased utilization of glucose. Lactate concentrations in the media at low or normal glucose concentrations exceeded normoxic levels, but higher glucose concentrations (15-30 mmol/L) failed to increase lactate levels further. Values of adenosine triphosphate for hypoxic astrocytes treated with high glucose concentrations were significantly higher than those of astrocytes with zero or low glucose levels. In cultures exposed to hypoxia and high glucose levels (30 mmol/L), no cellular injury was observed before 48 hours of hypoxia. Lactate concentrations in the media increased during the first 24 hours of hypoxia and reached steady state. The pH of the media decreased to 6.4 after 24 hours and 5.5 at 48 hours. The latter pH was concomitant with a marked increase in extracellular lactate dehydrogenase activity. Hyperosmotic mannitol failed to protect cultured astrocytes against hypoxia. CONCLUSIONS: Hypoxic injury to mature astrocytes was reduced by the presence of 15-60 mmol/L glucose in the medium during 24-30 hours of hypoxia. Injury occurred when the pH of the medium was < 5.5. This protection was not afforded by the hyperosmotic effect of high glucose concentrations, nor was the hypoxic injury at later time periods with 30 mmol/L glucose mediated solely by lactate accumulation.

Adenosine Triphosphate↗
PubMed1992

Oral ketamine preanesthetic medication in children.

The authors sought to define a dose of oral ketamine that would facilitate induction of anesthesia without causing significant side effects. Forty-five children (ASA Physical Status 1 and 2; aged 1-7 yr) were assigned randomly in a prospective, double-blind fashion to three separate groups that received either 3 mg/kg, 6 mg/kg, or no ketamine mixed in 0.2 ml/kg cola-flavored soft drink. They also were evaluated preoperatively and postoperatively for acceptance of oral ketamine as a premedicant, reaction to separation from parents, emotional state, and emergence phenomena. The authors detected no episodes of respiratory depression, tachycardia, or arterial hemoglobin desaturation before, during, or after surgery. The 6 mg/kg dose was well accepted; provided uniform, predictable sedation within 20-25 min; and allowed calm separation from parents and good induction conditions. The 3 mg/kg dose did not always cause sedation and calm separation from parents. Neither dose of ketamine increased the incidence of laryngospasm, prolonged recovery times, or caused emergence phenomena. The authors conclude that an oral dose of 6 mg/kg ketamine is easily administered and well accepted in young children and provides predictable, satisfactory premedication without significant side effects.

Administration, Oral↗
PubMed1992

Selective brain cooling during and after prolonged global ischemia reduces cortical damage in rats.

BACKGROUND AND PURPOSE: Studies of the cerebroprotective effects of selective brain cooling have failed to show amelioration of ischemic injury in the cerebral cortex. This study was designed to test the hypothesis that mild-to-moderate selective brain cooling initiated after the onset of global brain ischemia in rats protects the cerebral cortex and improves neurological outcome. METHODS: Global forebrain ischemia for 30 minutes in 27 fasted adult male Wistar rats was achieved by bilateral carotid occlusion and hypotension. In group 1, brain temperature, measured in the temporalis muscle, was maintained at 37-38 degrees C throughout the experiment. In group 2, brain temperature fell spontaneously during ischemia to 34.7 +/- 0.1 degrees C and rose spontaneously to 36-37 degrees C after 10 minutes of recirculation. In group 3, brain temperature was lowered with ice packs placed around the head after 15 minutes of ischemia to 24.1 +/- 0.9 degrees C by the end of ischemia, maintained at 30.0 +/- 1.0 degrees C for the first hour of recirculation, then allowed to rise to 36-37 degrees C. RESULTS: Seven-day survival was 0% (0 of 6) in group 1, 73% (8 of 11) in group 2, and 100% (6 of 6) in group 3. Severity of neuronal damage was less in group 2 than in group 1 in the cortex (p < 0.05) and hippocampal CA1 (p < 0.05) and CA3 regions (p < 0.05). Group 3 had less neuronal damage than group 2 in both cortex (p < 0.02) and striatum (p < 0.02). Furthermore, postischemic weight loss was less and neurobehavioral scores were significantly higher in group 3. CONCLUSIONS: This study shows that selective brain cooling increases survival from prolonged global ischemia and reduces neuronal injury in the cerebral cortex as well as the striatum and hippocampus.

Animals↗
PubMed1991

Intracranial pressure and brain redox balance in rabbits.

The effects of elevated intracranial pressure (ICP) on intracellular oxygenation and cerebrocortical blood volume (CBV) were studied in rabbits. Intracellular oxygen (O2) concentration was assessed as the level of pyridine nucleotide concentration ([NADH]) oxidation/reduction balance and relative cerebrocortical blood volume (CBV) were measured with a fibreoptic fluororeflectometer probe placed on the cerebrocortical surface. Experiments were conducted in six urethane anaesthetized, normocarbic animals at different fractions of inspired O2 (FIO2). During gradual increases in ICP, [NADH] began to increase (representing decreased intracellular mitochondrial PO2) for all values of FIO2 as ICP exceeded a threshold of 18 +/- 2.2 cmH2O (P less than 0.05). The decline in intracellular oxygenation with elevated ICP was inversely related to FIO2 (P less than 0.05). With ICP greater than 18 +/- 2.2 cmH2O, intracellular mitochondrial oxygenation showed an improvement between an FIO2 of 0.21 and 0.5 (P less than 0.05) but increasing FIO2 from 0.5 to 1.0 resulted in no statistically significant improvement in tissue redox balance. The CBV, largely representing tissue capillary blood, increased when ICP reached greater 18 +/- 1.2 cmH2O probably reflecting local autoregulation or venous distension (P less than 0.05). However, above 30 +/- 1.1 cmH2O, CBV decreased (P less than 0.05). The results demonstrate the interdependence of inspired oxygen concentration, elevated ICP, and brain intracellular oxygenation, and suggest that brain oxygen utilization deteriorates above an ICP of about 18 cmH2O.

Animals↗
PubMed1990

Fructose-1,6-bisphosphate reduces ATP loss from hypoxic astrocytes.

Hypoxia caused injury and metabolic dysfunction of astrocytes, as indicated by a time-dependent loss of lactate dehydrogenase (LDH) activity and ATP content. The combination of 3.5 mM fructose-1,6-bisphosphate (FBP) and 7.5 mM glucose (GLC) reduced the decrease of ATP and prevented the loss of LDH. These data indicate that the combination of GLC + FBP protects astrocytes from hypoxia. The results also suggest that the maintainance of ATP concentration is the mechanism by which FBP prevents hypoxic injury.

Adenosine Triphosphate↗
PubMed1989

Hypoxia-induced dysfunctions and injury of astrocytes in primary cell cultures.

The effects of severe hypoxia were studied in a primary culture of astrocytes prepared from newborn rat cerebral cortex. Hypoxia was created by placing cultures in an airtight chamber that was flushed with 95% N2/5% CO2 for 15 min before being sealed. The hypoxic environment was maintained constant for up to 24 h. During the first 12 h of hypoxia, astrocytes showed no morphological changes by phase-contrast microscopy. After 18 h of hypoxia, some astrocytes in culture became swollen and started to detach from the culture dish. All cells in the culture were destroyed after 24 h of hypoxia. The lactate dehydrogenase level in the culture medium increased more than tenfold between 12 and 24 h of hypoxia. Glutamate uptake was inhibited 80% by similar hypoxic conditions. The cell volume of astrocytes, as measured by 3-O-methyl-[14C]-D-glucose uptake, was increased. These observations suggested cell membrane dysfunction. The malondialdehyde level of hypoxic cultures increased two-fold after 24 h of hypoxia. Verapamil (0.5 mM), furosemide (1 mM), indomethacin (1 mM), MgCl2 (10 mM), and mannitol (10 mM) reduced but never completely abolished the release of lactate dehydrogenase from hypoxic astrocytes. These data suggest multifactorial causes for severe injury in hypoxic astrocytes.

Animals↗
PubMed1989

Fructose-1,6-bisphosphate protects astrocytes from hypoxic damage.

To determine the effects of glucose and fructose-1,6-bisphosphate (FDP) on hypoxic cell damage, primary cultures of astrocytes were incubated for 18 h in an air-tight chamber that had been flushed with 95% N2/5% CO2 for 15 min before it was sealed. Cultures containing 7.5 mM glucose without FDP or FDP without glucose showed evidence of significant cell injury after 18 h of hypoxia (increased lactate dehydrogenase content in the culture medium; cell edema and disruption by phase-contrast microscopy). Cultures exposed to glucose + FDP had normal lactate dehydrogenase concentrations and appeared normal microscopically. Maximal protection of hypoxic cells occurred at 6.0 mM FDP. Lactate concentrations of the culture medium of hypoxic cells increased 2.5 times above normoxic control values when glucose was present, but neither FDP alone nor glucose + FDP caused the lactate concentrations to increase further. This implies that anaerobic glycolysis was not increased by adding FDP to the medium. Cell volumes (water space) measured with [14C]-3-0-methyl-D-glucose were normal with glucose + FDP in the culture medium of hypoxic cells but were significantly larger than normal when glucose alone was present. Increases in cell volume paralleled changes in lactate dehydrogenase in the culture medium. Uptake of [14C]FDP occurred rapidly in normoxic cells and was maximal after 5 min of incubation. The data indicate that the presence of glucose + FDP in the culture medium protects primary cultures of hypoxic astrocytes from cell damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

Effects of anaesthesia and surgery on the solubility of volatile anaesthetics in blood.

To determine the effects of anaesthesia and surgery on the solubility of volatile anaesthetics in blood, we measured the blood/gas partition coefficients of enflurane, halothane, isoflurane, and methoxyflurane in vitro in blood obtained from six healthy unpremedicated adults at three different times during isoflurane anaesthesia: awake; 20 minutes after induction of anaesthesia, but before surgical incision; and, 90 minutes after surgical incision. The blood/gas partition coefficients of the four volatile anaesthetics decreased significantly after induction of anaesthesia and after surgical incision (p less than 0.05). Values for haematocrit and the serum concentrations of albumin, globulin, and cholesterol decreased parallel to the decrease in blood/gas partition coefficients.

Adult↗
PubMed1986

Effects of fructose-1,6-diphosphate, glucose, and saline on cardiac resuscitation.

Severe hypoxemia causes respiratory and cardiac arrest, in part, because severe hypoxemia decreases glycolysis and adenosine triphosphate (ATP) production by a lactic acid-induced decrease in the activity of phosphofructokinase and glyceraldehyde-3-P dehydrogenase. Fructose-1,6-diphosphate (FDP) administration increases the ATP concentration of blood. The authors hypothesized that FDP might increase the number of rabbits that could be resuscitated from hypoxemic cardiac arrest. To test this hypothesis, heart rate, arterial pressure, left ventricular end-diastolic pressure, and blood gases and pH were measured during normoxemia (FIO2 = 0.21) and again during hypoxemia (FIO2 = 0.04) in 28 adult, white, New Zealand rabbits anesthetized with pentobarbital. With the onset of hypoxemia, we gave either 40 mg/kg of 5% FDP (n = 10), 5% glucose (n = 11), or an equal volume (2.5 ml) of normal saline (n = 7) intravenously and began a continuous infusion of 2.0 mg X kg-1 X min-1 of the same sugar or 0.12 ml/min of saline. FDP-treated rabbits breathed for 20.9 +/- 4.9 (mean +/- SEM) min after initiation of hypoxemia; glucose-treated rabbits breathed for 1.4 +/- 0.2 min, and saline-treated rabbits breathed 10.3 +/- 4 min. Cardiac arrest occurred 2.5 +/- 0.5 min after the onset of respiratory arrest in FDP-treated rabbits, 4.1 +/- 0.2 min in glucose-treated rabbits, and 2.9 +/- 0.4 min in saline-treated rabbits. We could resuscitate all ten FDP-treated rabbits; two of 11 glucose-treated (FDP vs. glucose, P less than 0.001); and one of seven saline-treated rabbits (FDP vs. saline, P less than 0.001) from cardiac arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Dynamics of expiration and gas trapping in rabbits during mechanical ventilation at rapid rates.

Mechanical ventilation at rapid rates may cause gas trapping by decreasing the time available for expiration. The volume of gas trapped within the lungs depends not only on the expiratory time, but also on the rate of emptying of the lungs. Because newborn infants are frequently ventilated at rapid rates, we examined the factors determining the rate of lung emptying, and thereby the development of gas trapping, at ventilatory rates of 40 to 120 breath/min in anesthetized and paralyzed rabbits. We found that flow and volume were related nonlinearly during the first segment of expiration, and linearly during the second segment. Only the second segment could therefore be described with a single time constant. The expiratory resistance of the respiratory system and endotracheal tube was up to 4.5 times greater than the inspiratory resistance, a finding explained by the higher transmural airway pressures during inspiration and by the dynamic effects of the increase in cross-sectional airway area at the junction of endotracheal tube and trachea. This high expiratory resistance lengthened the time constant of the second segment of expiration which, combined with the delay caused by the slow opening of the exhalation valve during the first segment, promoted gas trapping when the expiratory time was shortened.

Animals↗
PubMed1986

Effect of high-dose dopamine on urine output in newborn infants.

To achieve adequate arterial BP, adequate capillary filling time, and adequate peripheral pulses, hypotensive newborn infants often require higher doses of dopamine that reportedly reduce urine output in adults. Whether these larger doses of dopamine also reduce urine output in newborns is not known. Therefore, we determined the effects of administering high-dose dopamine (more than 20 micrograms/kg X min) on the urine output of 15 newborn infants. Five infants were studied prospectively and ten retrospectively. In the prospective study, urine output was determined as the dose of dopamine was increased; in the retrospective study, urine output was determined as the infants were being weaned from high doses of dopamine. Both data sets demonstrate that administering high-dosage dopamine does not reduce the urine output of sick newborn infants. Therefore, we conclude that doses of dopamine previously reported to decrease urine output in adults do not do so in sick newborn infants. Consequently, when necessary, high doses of dopamine may be used in sick newborn infants to achieve cardiovascular stability without reducing urine output.

Birth Weight↗
PubMed1986

Mean airway pressure and mean alveolar pressure during high-frequency jet ventilation in rabbits.

Mean airway pressure underestimates mean alveolar pressure during high-frequency oscillatory ventilation. We hypothesized that high inspiratory flows characteristic of high-frequency jet ventilation may generate greater inspiratory than expiratory pressure losses in the airways, thereby causing mean airway pressure to overestimate, rather than underestimate, mean alveolar pressure. To test this hypothesis, we ventilated anesthetized paralyzed rabbits with a jet ventilator at frequencies of 5, 10, and 15 Hz, constant inspiratory-to-expiratory time ratio of 0.5 and mean airway pressures of 5 and 10 cmH2O. We measured mean total airway pressure in the trachea with a modified Pitot probe, and we estimated mean alveolar pressure as the mean pressure corresponding in the static pressure-volume relationship to the mean volume of the respiratory system measured with a jacket plethysmograph. We found that mean airway pressure was similar to mean alveolar pressure at frequencies of 5 and 10 Hz but overestimated it by 1.1 and 1.4 cmH2O at mean airway pressures of 5 and 10 cmH2O, respectively, when frequency was increased to 15 Hz. We attribute this finding primarily to the combined effect of nonlinear pressure frictional losses in the airways and higher inspiratory than expiratory flows. Despite the nonlinearity of the pressure-flow relationship, inspiratory and expiratory net pressure losses decreased with respect to mean inspiratory and expiratory flows at the higher rates, suggesting rate dependence of flow distribution. Redistribution of tidal volume to a shunt airway compliance is thought to occur at high frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Pulmonary mechanics during rapid mechanical ventilation in rabbits with saline-lavaged lungs.

Infants with respiratory failure are frequently mechanically ventilated at rates exceeding 60 breaths/min. We analyzed the effect of ventilatory rates of 30, 60, and 90 breaths/min (inspiratory times of 0.6, 0.3, and 0.2 s, respectively) on the pressure-flow relationships of the lungs of anesthetized paralyzed rabbits after saline lavage. Tidal volume and functional residual capacity were maintained constant. We computed effective inspiratory and expiratory resistance and compliance of the lungs by dividing changes in transpulmonary pressure into resistive and elastic components with a multiple linear regression. We found that mean pulmonary resistance was lower at higher ventilatory rates, while pulmonary compliance was independent of ventilatory rate. The transpulmonary pressure developed by the ventilator during inspiration approximated a linear ramp. Gas flow became constant and the pressure-volume relationship linear during the last portion of inspiration. Even at a ventilatory rate of 90 breaths/min, 28-56% of the tidal volume was delivered with a constant inspiratory flow. Our findings are consistent with the model of Bates et al. (J. Appl. Physiol. 58: 1840-1848, 1985), wherein the distribution of gas flow within the lungs depends predominantly on resistive factors while inspiratory flow is increasing, and on elastic factors while inspiratory flow is constant. This dynamic behavior of the surfactant-depleted lungs suggests that, even with very short inspiratory times, distribution of gas flow within the lungs is in large part determined by elastic factors. Unless the inspiratory time is further shortened, gas flow may be directed to areas of increased resistance, resulting in hyperinflation and barotrauma.

Animals↗
PubMed1986

Cardiovascular effects of d-tubocurarine and pancuronium in newborn lambs during normoxia and hypoxia.

Nondepolarizing muscle relaxants are administered to hypoxic neonates (including those with severe cyanotic congenital heart disease) to reduce oxygen consumption. However, it is unknown whether paralysis actually reduces oxygen consumption or whether the drugs used affect the cardiovascular system of neonates. Therefore, we studied the effects of d-tubocurarine and pancuronium induced muscle paralysis on oxygen consumption, cardiac output, and tissue oxygen delivery in healthy normoxic and hypoxic 1- to 3-day-old lambs. We measured intravascular pressures, cardiac output and its distribution (microspheres), and blood gases and pH during: 1) spontaneous respiration with room air (control); 2) spontaneous respiration with a Pao2 of 27-33 mm Hg (hypoxia); 3) mechanical ventilation with room air; 4) mechanical ventilation with room air and paralysis with d-tubocurarine (0.3 mg/kg) or pancuronium (0.1 mg/kg); and 5) mechanical ventilation with hypoxia and paralysis. Mechanical ventilation, with or without muscle paralysis, had no effect on the oxygen delivery or oxygen consumption of normoxic animals. Hypoxia and spontaneous ventilation had no effect on oxygen consumption, but hypoxia, paralysis, and mechanical ventilation reduced it 35% (p less than 0.002 d-tubocurarine) and 50% (p less than 0.001 pancuronium). Cardiac output was unaffected by oxygenation, mechanical ventilation, or muscle paralysis. However, blood flow to the brain and heart increased during hypoxia, which maintained normal oxygen delivery to these organs. During hypoxia and spontaneous ventilation, mean pulmonary arterial pressures increased 34% (d-tubocurarine) and 54% (pancuronium) above control; during hypoxia, muscle paralysis, and mechanical ventilation, it increased 81%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗