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Biomedical subjects

C A Gleason

Publications and source records attributed to C A Gleason.

At least 55 records · Page 3Linked to original sources
PubMed1989

Cerebral and peripheral circulatory responses to intracranial hypertension in fetal sheep.

Fetal head compression during normal labor can increase intracranial pressure (ICP). We studied the cerebral and peripheral blood flow responses to ICP elevation in utero in chronically catheterized fetal sheep using the radiolabeled microsphere technique. ICP was elevated, stepwise, in increments of 6 +/- 1 mm Hg by infusion of artificial cerebrospinal fluid into a lateral ventricle. When ICP was raised to within 28 mm Hg of baseline mean arterial blood pressure (i.e., ICP above 22 mm Hg), arterial pressure began to increase. Above this ICP level, up to 41 mm Hg, mean cerebral perfusion pressure was maintained by equivalent increases in arterial pressure. Cerebral blood flow and O2 uptake at the highest ICP levels were not different from baseline values. Changes in peripheral organ blood flow were graded according to the level of ICP. At the highest level (ICP = 41 mm Hg), renal, gastrointestinal, and skin blood flow decreased by 68%, 69%, and 65%, respectively. Myocardial and adrenal blood flow doubled, whereas heart rate and cardiac output were unchanged. Placental blood flow increased in proportion to arterial pressure. Arterial plasma epinephrine, norepinephrine and arginine vasopressin increased by nearly two orders of magnitude. Therefore, as ICP approaches baseline mean arterial pressure, fetal lambs are capable of sustaining cerebral perfusion by initiating profound visceral vasoconstriction without curtailing placental blood flow. Since cerebral O2 uptake was maintained, there is no evidence that stimulation of the peripheral response requires pronounced cerebral ischemia. This highly developed Cushing response may be important for ensuring cerebral viability when the fetal head is compressed during parturition.

Animals↗
PubMed1988

Fetal cerebral responses to ventilation and oxygenation in utero.

Previous studies have shown that cerebral oxygen consumption (CMRO2) increases by nearly 50% at birth. The perinatal factors responsible for this increase are unknown; however, one possibility is that fetal CMRO2 is constrained by the normal intrauterine arterial PO2 (PaO2) of approximately 20 mmHg. We investigated this possibility in seven near-term chronically instrumented fetal sheep (131-138 days gestation) in which we inserted vascular catheters and an endotracheal tube. After 1-3 days recovery, we measured cerebral blood flow (CBF) with radiolabeled microspheres and calculated CMRO2. Measurements were made in utero under three conditions for each fetus: 1) nonventilated control; 2) ventilation with 3% O2-5% CO2-92% N2; and 3) ventilation with an inspired oxygen concentration sufficient to raise fetal PaO2 to normal newborn levels (mean 73 mmHg). A calf lung surfactant extract (CLSE) was instilled into the endotracheal tube of the fetus before ventilation to ensure adequate levels of alveolar surfactant and to maintain stable pH and arterial PCO2. The results showed that increasing fetal arterial PO2 to postnatal levels did not consistently increase CMRO2. CBF decreased as arterial O2 content (CaO2) rose, with an inverse hyperbolic response similar to that previously found to relate CBF to CaO2 during fetal hypoxic hypoxia. This indicates that the normally low intrauterine PaO2 does not intrinsically limit CMRO2 and implies that the rapid increase in CMRO2 at birth reflects the activation of specific cellular and physiological processes at (or near) this unique developmental event.

Animals↗
PubMed1988

Indomethacin and patent ductus arteriosus: effects on renal function in preterm lambs.

To examine the independent effects of a patent ductus arteriosus and of indomethacin therapy on the renal function of the preterm newborn, we created a preterm lamb model in which ductus diameter could be regulated. We studied 24 preterm newborn lambs. Eight lambs (group 1) had their ductus closed at delivery and received no indomethacin. Eight lambs (group 2) had their ductus closed and then received indomethacin (0.3 mg/kg) at 5.5 h; eight lambs (group 3) had their ductus kept open and then received indomethacin at 5.5 h. Hemodynamic and renal function measurements were made at 5 h (pretreatment) and at 12.5 h. In group 2 lambs there was a significant reduction in inulin clearance (GFR) and osmolal clearance after indomethacin. In contrast, lambs with an open ductus (group 3), when compared with lambs with a closed ductus (groups 1 and 2) at 5 h, already had significantly decreased blood pressure, GFR, urine volume, and osmolal clearance. Following indomethacin treatment, group 3 lambs showed no further decrease in renal function. We suggest that in preterm lambs with patent ductus, the apparent lack of renal dysfunction following indomethacin treatment reflects underlying diminished renal function.

Animals↗
PubMed1987

Prostaglandins and the developing kidney.

Prostaglandins PGE2, PGD2, PGI2, and PGF2 alpha, as well as thromboxanes and leukotrienes, are synthesized by the fetal and neonatal kidney. The major prostaglandin, PGE2, PGD2, and PGI2, increase RBF, free water clearance, urine flow, and natriuresis. Alterations in the synthetic and catabolic activity of renal prostaglandins with advancing gestational and postnatal age occur along with concomitant alterations in RBF, GFR, and water and electrolyte excretion, suggesting that the prostaglandins play an important role in renal functional development. Indomethacin treatment may affect both fetal and neonatal renal function. Long-term maternal indomethacin treatment may decrease fetal urine output enough to alter amniotic fluid volume. Neonatal indomethacin therapy may cause transient dose-related renal dysfunction characterized by a decrease in urine output, but this renal dysfunction also depends in part on dosage, timing of therapy, and the cardiovascular and renal status of the infant prior to treatment. New areas of research interest include urinary prostaglandins as a marker for development of essential hypertension, and the possible interaction between antenatal steroids and renal function in the newborn.

Animals↗
PubMed1986

Oxygenation does not stimulate hepatic gluconeogenesis in fetal lambs.

We have previously shown that the healthy fetal lamb liver does not release glucose and does not demonstrate gluconeogenesis. Shortly after birth, however, the liver releases glucose both by glycogenolysis and by gluconeogenesis. Previously it has been suggested that increased oxygen availability stimulates hepatic gluconeogenesis at birth. To test this hypothesis, we increased fetal arterial blood pO2 by ventilating the fetus with high oxygen gas mixtures in utero. We placed intravascular catheters in the right or left hepatic vein, umbilical vein, inferior vena cava, and descending aorta and inserted a large polyvinyl tube into the trachea of seven fetal lambs at 134 +/- 2.2 days gestation. Studies were done several days after surgery. 14C-lactate was infused intravenously and 14C-glucose concentrations were measured in hepatic venous and umbilical venous blood during a control period, during ventilation with 5% CO2, 3% O2, 92% N2, and then during ventilation with 5% CO2 and 95% O2. The difference between these two measurements represented hepatic gluconeogenesis. Arterial blood glucose concentrations and blood gases were also measured during each study period. Ventilation with 3% O2 did not significantly change arterial PO2 but ventilation with 95% oxygen increased mean arterial pO2 from a control of 16.7 to 156.3 torr. Mean arterial blood glucose concentration increased significantly from a control of 11.9 to 17.6 mg/dl during ventilation with 3% O2 and to 19.1 mg/dl during ventilation with 95% O2. However, the hepatic-umbilical venous 14C-glucose concentration difference was not significant when control values were compared with each ventilation period. We conclude that an acute increase in fetal oxygenation does not stimulate hepatic gluconeogenesis in near-term fetal lambs.

Animals↗
PubMed1985

Hepatic oxygen consumption, lactate uptake, and glucose production in neonatal lambs.

Previous studies have evaluated neonatal hepatic metabolism in vitro, and neonatal hepatic oxygen consumption has been measured in vivo, but direct measurements of neonatal hepatic metabolism have not been reported. We studied seven neonatal lambs at age 7-10 days after placing catheters chronically in the hepatic vein, portal vein, descending aorta, left ventricle, and inferior vena cava. Hepatic blood flow was measured by the radioactive microsphere technique. Oxygen consumption and glucose and lactate fluxes were measured using the Fick principle. 14C-lactate was infused intravenously and lactate and glucose specific activities were measured and used to calculate hepatic gluconeogenesis from lactate. Neonatal hepatic blood flow was 254.5 +/- 50.3 ml/min/100 g (mean +/- SD) with 5.4 +/- 4.6% from the hepatic artery and 94.6 +/- 4.6% from the portal vein. Hepatic oxygen consumption was 7.2 +/- 2.4 ml/min/100 g and oxygen extraction was 44.9 +/- 15.4%. Oxygen extraction correlated inversely with oxygen delivery. In the seven lambs, there was net hepatic lactate uptake of 10.2 +/- 5.0 mg/min/100 g (1.13 +/- 0.56 mM) and hepatic glucose production of 30.8 +/- 11.3 mg/min/100 g (1.71 +/- 0.62 mM). In the five lambs in which hepatic gluconeogenesis was measured, 12.4 +/- 5 mg (1.37 +/- 0.56 mM) of lactate was converted to glucose per 100 g liver, accounting for 38.4% of the hepatic glucose production in these lambs. Blood flow and oxygen and substrate delivery to the neonatal liver are lower than those to the fetal liver but the neonatal liver extracts more oxygen and substrates and is able to produce glucose by gluconeogenesis from lactate.

Animals↗
PubMed1985

Lactate uptake by the fetal sheep liver.

Lactate is produced by the sheep placenta and is an important metabolic substrate for fetal sheep. However, lactate uptake and release by the fetal liver have not been assessed directly. We measured lactate flux across the liver in 16 fetal sheep at 129 (120-138) days gestation that had catheters chronically maintained in the fetal descending aorta, inferior vena cava, right or left hepatic vein, and umbilical vein. Lactate and hemoglobin concentrations and oxygen saturation were measured in blood drawn from all vessels. Umbilical venous, portal venous, and hepatic blood flow were measured by injecting radionuclide-labeled microspheres into the umbilical vein while obtaining a reference sample from the descending aorta. We found net hepatic uptake of lactate (5.0 +/- 4.4 mg/min per 100 g liver). A large quantity of lactate was delivered to the liver (94.2 +/- 78.1 mg/min per 100 g), so that the hepatic extraction of lactate was only 7.7 +/- 6.5%. Hepatic oxygen consumption was 3.18 +/- 3.3 ml/min per 100 g, and the hepatic lactate/oxygen quotient was 2.07 +/- 1.54. There was no significant correlation between hepatic lactate uptake and hepatic lactate or glucose delivery, hepatic oxygen consumption, hepatic blood flow, hepatic glucose flux, total body oxygen consumption, arterial pH, oxygen content, or oxygen saturation. There was, however, a significant correlation between hepatic lactate uptake and umbilical lactate uptake (r = 0.74, P less than 0.005) such that net hepatic lactate uptake was nearly equivalent to that produced across the umbilical-placental circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Gluconeogenesis by the fetal sheep liver in vivo.

Hepatic gluconeogenesis is an important source of glucose postnatally. Whether hepatic gluconeogenesis contributes to fetal glucose supply has not been studied directly in vivo. Previous studies of gluconeogenesis in fetal sheep have assessed total fetal glucose production, and the results have been controversial. To assess the specific role of the liver in gluconeogenesis in fetal sheep, we placed catheters in the right or left hepatic vein, umbilical vein and the inferior vena cava of six fetal sheep (mean gestational age 134 days) and infused a radioactive gluconeogenic substrate (14C-lactate or 14C-alanine) into the fetal inferior vena cava. We measured 14C-glucose radioactivity (dpm/ml) in the right or left hepatic vein and calculated the arteriovenous difference in 14C-glucose radioactivity (dpm/ml) across the right or left liver lobe. We found that only 0.35% of the 14C substrates perfusing either the right or the left hepatic lobe of the fetal liver were converted to 14C-glucose. Even when considerable glucose was released by the liver, the percentage of substrates converted to glucose remained very low (maximum 1.7%), indicating that gluconeogenesis did not contribute significantly to the glucose released. We conclude that gluconeogenesis by the fetal liver contributes negligibly to the glucose supply in fetal sheep.

Alanine↗
PubMed1984

Rapid electroenzymatic measurement of lactate in microsamples of spinal fluid.

A lactate sensor, which makes possible rapid direct measurement of L-lactate in small samples of spinal fluid, has been developed. This enzyme electrode gives a linear current output as a function of hydrogen peroxide generated by a lactate oxygen oxidoreductase sandwiched between two membranes. The membranes serve to support the oxidase, prevent the diffusion of soluble electroactive species such as urate, ascorbate, and phenolic drugs such as acetaminophen, and to form a diffusion-limited path for the lactate. A 10 or 25 microL sample of spinal fluid is injected into a 350 microL thermostated chamber containing a suitable buffer and the electrode's sensing surface. The method has been tested by analysis of spinal fluid, with amounts of lactate up to 15 mmol/L, by comparison with a photoenzymatic method. A correlation coefficient of 0.999 was found. With a new cellulose ester membrane, acetaminophen levels up to 10 mmol/L did not interfere. A YSI glucose analyzer can be converted to a lactate analyzer by changing the O-ring mounted enzyme transducer membrane.

Electrodes↗
PubMed1983

Preparation- or intention-to-act, in relation to pre-event potentials recorded at the vertex.

Pre-event potentials were compared in the same subject, for 3 types of forewarned events, in which the foreperiod for orienting or attention began several seconds before the event. All of these trials involved similar non-motor components (expectancy, attentiveness, general orienting to a salient stimulus) but differed in whether motor or non-motor responses were required. A prominent and consistent slow negative shift preceded the pre-set time for a motor response, even when the subject 'vetoed' his intention to act shortly before the pre-set time. Pre-event potentials were absent, or small and brief, when the event was a task-related skin stimulus not involving preparation to move. The findings selectively support the view that mental preparation/intention to act is a necessary and perhaps dominant process associated with the vertex-recorded pre-event, slow negative potential. They also show that such a pre-event potential can appear even when the subject knows he is going to veto his developing intention to act and does not actually move.

Adult↗
PubMed1983

Time of conscious intention to act in relation to onset of cerebral activity (readiness-potential). The unconscious initiation of a freely voluntary act.

The recordable cerebral activity (readiness-potential, RP) that precedes a freely voluntary, fully endogenous motor act was directly compared with the reportable time (W) for appearance of the subjective experience of 'wanting' or intending to act. The onset of cerebral activity clearly preceded by at least several hundred milliseconds the reported time of conscious intention to act. This relationship held even for those series (with 'type II' RPs) in which subjects reported that all of the 40 self-initiated movements in the series appeared 'spontaneously' and capriciously. Data were obtained in at least 6 different experimental sessions with each of 5 subjects. In series with type II RPs, onset of the main negative shift in each RP preceded the corresponding mean W value by an average of about 350 ms, and by a minimum of about 150 ms. In series with type I RPs, in which an experience of preplanning occurred in some of the 40 self-initiated acts, onset of RP preceded W by an average of about 800 ms (or by 500 ms, taking onset of RP at 90 per cent of its area). Reports of W time depended upon the subject's recall of the spatial 'clock-position' of a revolving spot at the time of his initial awareness of wanting or intending to move. Two different modes of recall produced similar values. Subjects distinguished awareness of wanting to move (W) from awareness of actually moving (M). W times were consistently and substantially negative to, in advance of, mean times reported for M and also those for S, the sensation elicited by a task-related skin stimulus delivered at irregular times that were unknown to the subject. It is concluded that cerebral initiation of a spontaneous, freely voluntary act can begin unconsciously, that is, before there is any (at least recallable) subjective awareness that a 'decision' to act has already been initiated cerebrally. This introduces certain constraints on the potentiality for conscious initiation and control of voluntary acts.

Adult↗
PubMed1983

Optimal position for a spinal tap in preterm infants.

Inasmuch as spinal taps in preterm infants are frequently accompanied by clinical deterioration, the optimal position for this procedure was investigated. Three positions were each randomly assigned for five minutes to 17 healthy preterm infants without a spinal tap actually being performed: (1) lateral recumbent with full flexion (flexed position), (2) lateral recumbent with partial neck extension (extended position), and (3) sitting with head support and spine flexion (upright position). Transcutaneous PO2 and PCO2 were monitored in all infants, minute ventilation (VI) in seven, and heart rate and blood pressure in ten infants. Mean transcutaneous PO2 decreased in each of the three positions. This decrease was significantly greater in the flexed (28 +/- 8 mm Hg) as compared with the extended (18 +/- 8 mm Hg, P less than .001) and upright (15 +/- 11 mm Hg, P less than .001) positions. Mean transcutaneous PCO2 increased only in the flexed position (3 +/- 4 mm Hg, P less than .005) and levels were still elevated five minutes after that position had been discontinued. The consistent decrease in transcutaneous PO2 was accompanied by a variable effect of positioning on VI and there were no episodes of airway obstruction or apnea greater than 10 seconds. Heart rate increased in each position whereas blood pressure remained unchanged. These data suggest that although hypoventilation may contribute to the observed decrease in transcutaneous PO2, ventilation/perfusion imbalance appears to be the major mechanism. As spinal taps performed in the widely accepted flexed position carry the greatest risk of potential morbidity, it is recommended that this position be modified with neck extension or that spinal taps be performed in the upright position.

Carbon Dioxide↗
PubMed1982

Readiness-potentials preceding unrestricted 'spontaneous' vs. pre-planned voluntary acts.

The nature of readiness-potentials (RPs) that may be associated with fully endogenous, 'freely' voluntary acts was investigated. Restriction on when to act were eliminated and instructions fostered 'spontaneity.' The 'self-initiated' RPs exhibited in these conditions were categorizable into two (possibly three) types, all of which could be exhibited by the same subject. Type I had an early onset at about -1050 +/- 175 msec and a long ramp-like form, resembling self-paced RPs. In type II the main negative shift began at about -575 +/- 150 msec, and at about -240 +/- 50 msec in type III. Type II partially resembled the similarly timed NS' component in self-paced RPs. For acts produced at known, preset times, in which freedom of choice was eliminated but planning to act was required, RPs resembled self-initiated type I RPs and self-paced RPs. All RPs were maximal at the vertex, especially type II even though it was also bilaterally asymmetrical. These distributions suggest that cortical areas other than area 4 and 6 contribute importantly, especially to type II. All RPs, whether in self-initiated or pre-planned acts, appear related specifically to preparation for a motor action. When task-related skin stimuli replaced self-initiated movements, under similar conditions of attentiveness (and expectancy), there were either no or relatively small event-preceding-slow potential shifts. All post-stimulus P300 waves were very large. Two volitional processes are postulated: process I is associated with development of pre-planning or preparation to act in the near future (seconds), whether voluntary choice is present (type I RPs) or absent (pre-set RPs); process II, with an onset at roughly 0.5 sec before the act, is associated more uniquely with voluntary choice and with the more specific as well as endogenous urge or intention to act; it can be present in the comparative absence of or in sequence and overlapping with process I.

Brain↗
PubMed1977

Suppression of an eplieptiform type of electrocortical activity in the rat by stimulation in the vicinity of locus coeruleus.

Stimulation of the locus coeruleus, or in the vicinity of this nucleus or of its ascending tracts, could markedly suppress the appearance of epileptiform-like ECoG bursts. The latter were induced in rats by a subconvulsive dose of pentylenetetrazol. Electrode sites were identified histologically. A unilateral stimulus suppressed bursts bilaterally. An individual burst already in progress could be aborted, stopping within less than 0.5-1 sec after onset of a stimulus train. The antiepileptiform actions occurred with no evidence of any desynchronizing effect of the stimulus on the resting ECoG; they appear to be different in sites of origin and nature from those reported for stimulation of the reticular activating system. It is proposed that stimulation of the ascending noradrenergic system in the brain stem may limit the development and spread of hyperexcitatory, epileptiform states.

Animals↗