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Biomedical subjects

E B Olson

Publications and source records attributed to E B Olson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Phrenic responses to isocapnic hypoxia in adult rats following perinatal hyperoxia.

The purpose of this study was to test the hypothesis that carotid body-mediated, phrenic nerve responses to hypoxia are attenuated in adult rats that had been previously exposed to perinatal hyperoxia (one month of 60% O2; perinatal treated rats.) Integrated phrenic nerve responses to strictly controlled isocapnic hypoxia were measured in urethane-anesthetized, vagotomized, paralyzed and ventilated adult rats 2-5 months after perinatal hyperoxia, before and after bilateral carotid denervation. In untreated control rats, phrenic burst frequency, peak amplitude of integrated phrenic activity and minute phrenic activity increased 21 +/- 3 bursts/min (mean +/- SE), 158 +/- 20% and 279 +/- 34%, respectively, during hypoxia (50 Torr PaO2). In contrast, phrenic nerve activity increased to a significantly lesser degree in perinatal treated rats (frequency, 12 +/- 2 bursts/min; amplitude, 87 +/- 13%; minute activity, 150 +/- 19%; all P < 0.05). Hypoxic phrenic responses were abolished by carotid degeneration in both rat groups. In rats exposed to hyperoxia as adults, hypoxic phrenic responses were not attenuated versus untreated control rats. The data indicate that carotid body-mediated, isocapnic hypoxic chemoreflexes are impaired in perinatal treated rats, an effect unique to development. These effects cannot be accounted for by differences in blood gases (O2 or CO2) or pulmonary mechanics.

Animals↗
PubMed1997

Developmental plasticity of the hypoxic ventilatory response.

This paper will describe recent studies concerning the existence of developmental plasticity in the hypoxic ventilatory control system and the locus of the functional impairment following perinatal sensory suppression. Suppression of peripheral arterial chemoreceptor activity was achieved by exposing rats to hyperoxia (60% O2) for the first month of life; all measurements were conducted 2-5 months after the exposure (perinatal treated rats). Hypoxic (but not hypercapnic) ventilatory responses were severely attenuated in awake perinatal treated rats, but not in rats exposed to hyperoxia as adults, indicating that the persistent effect is unique to development and is not the nonspecific result of O2 toxicity. Impairments of the hypoxic ventilatory response due to changes in pulmonary mechanics, gas exchange or central integration of carotid chemoafferent inputs were all ruled out as primary causal factors. However, a persistent impairment of carotid chemotransduction in perinatal treated rats was apparent. These studies suggest that the hypoxic ventilatory response is susceptible to developmental plasticity, and that a carotid chemoreceptor deficit is the primary cause. These findings may have important clinical implications for patients subjected to excessive O2 therapy during neonatal intensive care.

Animals↗
PubMed1996

Attenuation of the hypoxic ventilatory response in adult rats following one month of perinatal hyperoxia.

1. This study was designed to test the hypothesis that perinatal suppression of peripheral arterial chemoreceptor inputs attenuates the hypoxic ventilatory response in adult rats. Perinatal suppression of peripheral chemoreceptor activity was achieved by exposing rats to hyperoxia throughout the first month of life. 2. Late-gestation pregnant rats were housed in a 60% O2 environment, exposing the pups to hyperoxia from several days prior to birth until they were returned to normoxia on postnatal day 28. These perinatally treated rats were then reared to adulthood (3-5 months old) in normoxia. In addition to the mother rats, adult male rats were also exposed to hyperoxia, creating an adult-treated control group. Two to four months after the hyperoxic exposure, treated rats were compared with untreated male rats of similar age. 3. A whole-body, flow-through plethysmograph was used to measure hypoxic and hypercapnic ventilatory responses of the unanaesthetized adult rats. In moderate hypoxia (arterial oxygen partial pressure, Pa,O2 approximately 48 mmHg). VE (minute ventilation) and the ratio VE/VCO2 (ventilation relative to CO2 production) increased by 16.7 +/- 4.0 and 35.4 +/- 3.4%, respectively, in perinatal-treated rats (means +/- S.E.M.), but increased more in untreated control rats (51.4 +/- 2.8 and 83.1 +/- 4.3%; both P < 10(-6)). 4. In contrast to the impaired hypoxic ventilatory response, ventilatory responses to hypercapnia (5% CO2) were similar between untreated control and perinatal-treated rats. 5. Impaired hypoxic responsiveness was unique to the perinatal-treated rats since hypoxic ventilatory responses were not attenuated in adult-treated rats. 6. The results indicate that ventilatory responses to hypoxaemia are greatly attenuated in adult rats that had experienced hyperoxia during their first month of life, and suggest that normal hypoxic ventilatory control mechanisms are susceptible to developmental plasticity.

Animals↗
PubMed1994

Physiological dead space increases during initial hours of chronic hypoxemia with or without hypocapnia.

A whole body plethysmograph was used to determine the minute ventilation-to-CO2 production ratio (VE/VCO2) of intact unrestrained unanesthetized adult male Sprague-Dawley rats during 7 days of hypoxemia (arterial PO2 approximately 50 Torr). In one set of rats, normocapnia (arterial PCO2 approximately 40 Torr) was maintained. Arterial blood gases and acid-base status were determined, and arterial PCO2 was used to calculate alveolar ventilation-to-VCO2 ratio (VA/VCO2) in all situations when inhaled CO2 was not elevated. In normoxia VE/VCO2 = 25 +/- 1 (mean +/- 95% confidence limits); after 12 h of hypoxemia, VE/VCO2 was maximal, 61 +/- 5 in hypoxemic hypocapnia and 200 +/- 55 in hypoxemic normocapnia. Between 2 and 7 days of hypoxemia, VE/VCO2 had plateaued, 42 +/- 3 in hypoxemic hypocapnia and 95 +/- 19 in hypoxemic normocapnia. Dead space-to-tidal volume ratio (VD/VT) = (VE/VCO2 - VA/VCO2)/(VE/VCO2), and in normoxia VD/VT = 0.17 +/- 0.04. In hypoxemic hypocapnia, VD/VT measured between 1 and 5 h was 0.38 +/- 0.04. It remained elevated at 0.29 +/- 0.04 after 24 h, but after 4-7 days in hypoxemic hypocapnia, VD/VT had recovered to 0.15 +/- 0.03. It is postulated that the disproportionate increase in VE/VCO2 observed during the first 24 h of exposure to hypoxemic normocapnia (compared with elevated steady-state plateau levels maintained from 2 to 7 days sojourn) reflects an immediate transient increase of physiological dead space on exposure to hypoxemia.

Acclimatization↗
PubMed1989

Carotid body amine levels in goats exposed to hypoxia or hypercapnia.

The carotid body (CB) contains large amounts of several monoamines. There is considerable evidence that carotid body (CB) chemoreceptor function may be regulated by one or several of these monoamines. In order to test whether conditions stimulating the CB might change the CB content of these monoamines, we measured the norepinephrine, dopamine, 5-hydroxyindoleacetic acid, and 5-hydroxytryptamine content of carotid bodies collected from goats exposed to 4 h of either normoxic-normocapnic, hypoxic-normocapnic, or normoxic-hypercapnic gas mixtures. We found that there were no consistent changes in the levels of these amines associated with exposure to the test gases. These findings would not support the hypothesis that changes in these amine levels in the CB are responsible for the time-dependent changes in carotid chemoreceptor activity in goats exposed to 4 h of hypoxia.

Animals↗
PubMed1988

Separate effects of low carbon dioxide and low oxygen content on rat brain monoamine metabolism during hypoxemia.

Awake, adult male rats (some with chronically indwelling femoral artery catheters) were exposed for up to 7 days to one of three environments: a) normoxia (PIO2 = 155 Torr), b) hypoxic hypocapnia (PIO2 = 90 Torr), and c) hypoxic normocapnia (PIO2 = 73 Torr, PICO2 = 32 Torr), and arterial blood gas and acid-base status were documented. After 1 hour to 7 days, rats were sacrificed, and the time courses of the brain levels and turnovers of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine or 5HT) were determined in each condition. The transient decrease in monoamine levels seen on exposure to acute hypoxia was absent if normocapnia was maintained; 7 days hypoxia with or without hypocapnia resulted in increased monoamine levels. Normocapnia also prevented an immediate, sustained decrease in 5HT turnover and a delayed decrease in DA turnover which were observed in hypoxic hypocapnia. A delayed increase in 5HT turnover appeared to be due to hypoxia independent of PaCO2. Therefore, the initial, transient loss of mental acuity and some ventilatory adaptations observed during prolonged hypoxia may be a result of the decrease in PaCO2 rather than the decreased oxygen concentration.

Amines↗
PubMed1988

Carotid body excision significantly changes ventilatory control in awake rats.

We determined the effects of carotid body excision (CBX) on eupneic ventilation and the ventilatory responses to acute hypoxia, hyperoxia, and chronic hypoxia in unanesthetized rats. Arterial PCO2 (PaCO2) and calculated minute alveolar ventilation to minute metabolic CO2 production (VA/VCO2) ratio were used to determine the ventilatory responses. The effects of CBX and sham operation were compared with intact controls (PaCO2 = 40.0 +/- 0.1 Torr, mean +/- 95% confidence limits, and VA/VCO2 = 21.6 +/- 0.1). CBX rats showed 1) chronic hypoventilation with respiratory acidosis, which was maintained for at least 75 days after surgery (PaCO2 = 48.4 +/- 1.1 Torr and VA/VCO2 = 17.9 +/- 0.4), 2) hyperventilation in response to acute hyperoxia vs. hypoventilation in intact rats, 3) an attenuated increase in VA/VCO2 in acute hypoxemia (arterial PO2 approximately equal to 49 Torr), which was 31% of the 8.7 +/- 0.3 increase in VA/VCO2 observed in control rats, 4) no ventilatory acclimatization between 1 and 24 h hypoxia, whereas intact rats had a further 7.5 +/- 1.5 increase in VA/VCO2, 5) a decreased PaCO2 upon acute restoration of normoxia after 24 h hypoxia in contrast to an increased PaCO2 in controls. We conclude that in rats carotid body chemoreceptors are essential to maintain normal eupneic ventilation and to the process of ventilatory acclimatization to chronic hypoxia.

Acute Disease↗
PubMed1987

Naloxone accelerates the rate of ventilatory acclimatization to hypoxia in awake rats.

During ventilatory acclimatization to hypoxia in rats, PaCO2 progressively falls from about 40 torr in normoxia (PIO2 approximately equal to 150 torr) to a new steady-state at about 23 torr in chronic hypoxia (24 or more hours at PIO2 approximately equal to 90 torr). In acute (20 or 60 minutes) hypoxia naloxone treatment caused a hyperventilation greater than that caused by acute hypoxia alone. Following 20 minutes hypoxia, naloxone treated rats had a PaCO2 = 28.6 +/- 0.7 torr (mean +/- 95% confidence limits) which was significantly lower (P less than .001) than the saline treated PaCO2 = 31.0 +/- 0.6 torr. In contrast, in normoxia and at 24 hour hypoxia and at 20 minute return to normoxia following 24 hours hypoxia, naloxone treatment had no effect on PaCO2. We conclude that in the rat about one third of the ventilatory acclimatization to hypoxia is due to a progressively decreasing endogenous opioid-like inhibition of ventilation.

Adaptation, Physiological↗
PubMed1987

Immunological identification and effects of 3-methylcholanthrene and phenobarbital on rat pulmonary cytochrome P-450.

Rabbit antibodies to the phenobarbital (PB) inducible rat liver microsomal cytochrome P-450s b and e and to 3-methylcholanthrene (MC) inducible P-450c were used to examine the expression of these isozymes in rat lungs. Western blots of total lung microsomes demonstrated that about 40 pmol P-450b/mg protein (and no detectable P-450e) were present in lungs from control or MC treated rats and that pretreatment with PB caused a small but significant (P less than 0.05) increase in the expression of P-450b. Microsomes from control and PB treated lung contained minimal levels of P-450c, and MC induced this isozyme to 185 pmol/mg. Immunocytochemistry was used to demonstrate immunoreactivity to these isozymes in specific cell types. Neither P-450b nor P-450c was detectable in endothelial cells from control or PB treated lungs, but MC increased immunoreactivity to P-450c in pulmonary endothelial cells. Type II alveolar cells showed distinct immunoreactivity to P-450b and weak immunoreactivity to P-450c in control or PB treated rats. Individual Clara cells stained for either P-450c or P-450b in control, MC treated, and PB treated rats, and colocalization was observed in some cells. An increase in type II alveolar cell and Clara cell immunoreactivity to P-450c was observed after MC induction. Mast cells, identified by metachromatic Giemsa staining, appeared to react nonspecifically with both antisera. In conclusion, P-450c is highly inducible by MC in rat lung (detected in microsomes by Western blot), specifically in endothelial cells, Clara cells, and alveolar type II cells (as visualized by immunocytochemistry); and P-450b is present in rat lung microsomes, and immunoreactivity to this isozyme is localized in alveolar type II and Clara cells.

Animals↗
PubMed1987

Ventilatory adaptation to hypoxia occurs in serotonin-depleted rats.

To test the hypothesis that serotonin mediated respiratory activity is involved in ventilatory adaptation to hypoxia, rats were treated with parachlorophenylalanine (PCPA), a potent, long-acting inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin. In normoxia, a single, intraperitoneal injection of 300 mg PCPA/kg body weight decreased the Paco2 from a control level at 39.1 +/- 0.6 Torr (mean +/- 95% confidence limits) to 34.0 +/- 0.6 Torr measured during a period from 1 to 48 h following PCPA treatment. This PCPA-produced hyperventilation corresponds to an increase of 3.7 +/- 0.5 in the VA (BTPS)/Vco2 (STPD) ratio. Hyperventilation during ventilatory adaptation to hypoxia (PIO2 approximately equal to 90 Torr) was superimposed in an additive fashion on the underlying hyperventilation due to PCPA pretreatment. Specifically, PCPA pretreatment caused an average 3.5 +/- 1.2 increase in the VA/VCO2 ratio determined in acute (1 h) hypoxia, chronic (24 h) hypoxia and acute return to normoxia following chronic hypoxia. Since ventilatory adaptation to hypoxia occurred in rats treated with PCPA, the prolonged, serotonin mediated respiratory activity described by Millhorn et al. (1980b) is probably not important in ventilatory acclimatization to - or deacclimatization from - hypoxia.

Adaptation, Physiological↗
PubMed1987

The effects of post-exercise glucose and alanine ingestion on plasma carnitine and ketosis in humans.

1. Several studies have hypothesized that alanine decreases plasma ketone body levels by increasing availability of oxaloacetate, thus allowing acetyl groups to enter the tricarboxylic acid cycle and releasing co-enzyme A (CoA). 2. Four, fasted adult males exercised at 50% of their maximal oxygen consumption for 1.5 h, then ingested 100 g of either glucose or alanine 2 h into recovery. 3. Post-exercise ketosis had developed at 2 h into recovery, as shown by a significantly elevated concentration of beta-hydroxybutyrate in the plasma. At this time plasma free fatty acids were elevated above resting levels while plasma free carnitine concentrations had fallen below resting values. 4. After either alanine or glucose ingestion beta-hydroxybutyrate concentrations fell to the same extent. After the alanine load free carnitine increased above that seen in the glucose trial. Following either alanine or glucose ingestion free fatty acid levels fell; they remained at resting levels in the alanine trial but decreased below rest in the glucose trial. 5. We assume that plasma carnitine concentrations largely reflect the hepatic carnitine pools; therefore, elevations in the plasma free carnitine are probably the result of an increased utilization of acetyl CoA. The significant elevation in plasma free carnitine concentration found after alanine ingestion is consistent with the hypothesis that alanine increases the oxidation of acetyl CoA by providing oxaloacetate for the tricarboxylic acid cycle.

3-Hydroxybutyric Acid↗
PubMed1983

Uptake of metabolism of norepinephrine in isolated perfused fetal, newborn and adult rabbit lungs.

We compared the ability of isolated perfused lungs from previable, 26-day gestation, fetal rabbits; newborn rabbits (within 12 hours of birth) and 3 month old adult rabbits to metabolize a 20-second bolus of norepinephrine (NE). The concentration of NE infused was much below the Km for the NE uptake process to assure first order uptake kinetics. At these low concentrations no vasoactivity was observed. The retention time of a vascular marker dye was monitored as an index of pulmonary vascular surface area. In all three sizes of lungs perfusate flow was adjusted to produce an approximately 7 second dye retention time. At these flow adult and newborn lungs inactivate about 50 to 60 percent of the infused NE. In contrast, fetal rabbit lungs inactivate about 80 percent of the infused NE. We conclude that circulating NE is most avidly taken up and metabolized during fetal lung development. The physiologic significance of this fetal NE inactivation remains unknown.

Age Factors↗
PubMed1983

Monoamine neurotransmitter metabolism during acclimatization to hypoxia in rats.

The levels and turnovers of NE, DA and 5HT were determined in whole brain, brain stem, cervical and thoracic spinal cord and carotid bodies (CB) of rats exposed to from 1 h to 7 days of hypobaric hypoxia (PB = 450 torr). Monoamine levels decreased only transiently upon acute exposure to hypoxia. Monoamine turnover in the CNS was estimated from the average of (a) monoamine buildup following inhibition of catabolism, and (b) monoamine breakdown following inhibition of synthesis. Hypoxic effects on CNS monoamine turnover showed that: (a) NE was not affected; (b) DA was not affected in acute hypoxia, but was reduced to about 40% of normoxia control after 1-7 days hypoxia; (c) 5HT fell 50-60% during acute hypoxia but returned to and was maintained at control over 1-7 days of hypoxia; (d) acute restoration of normoxia following acute hypoxia restored 5HT and DA to control or above and in the acclimatized animal acute normoxia increased DA and 5HT turnover to about 1.4 and 1.8 X control. In the CB, DA levels gradually increased to 4 X control after 7 days of hypoxia and further increased to 6 X control upon acute restoration of normoxia. Changes in the metabolism of both central 5HT and CB DA may be related to the mechanisms mediating ventilatory acclimatization to chronic hypoxia.

Adaptation, Physiological↗
PubMed1983

Differences in the perinatal development of the isolated rabbit lungs' ability to inactivate vasoactive substances.

A 20-second bolus of serotonin (5-hydroxytryptamine, 5HT), prostaglandin E1 (PGE1) or norepinephrine (NE) was infused into the pulmonary arteries of lungs isolated from 26-day gestation fetal, newborn (within 12 h of birth), and young adult rabbits. In each case the concentration of the infused substrate was much less than the apparent Michaelis constant for the uptake process. At these low concentrations there was no observable vasoactivity. In order to assure a constant ratio of flow to capillary surface area (independent of lung size), perfusate flow was adjusted so that the retention time of a vascular dye was approximately 7 s. Under these conditions the isolated adult rabbit lungs inactivate a similar fraction (40-50%) of each of the substrates. In contrast, isolated newborn rabbit lungs inactivate about 20% of the infused PGE1, 90% of the 5HT, and 60% of the NE, and the nonventilated, previable fetal rabbit lungs inactivate about 20% of the infused PGE1, 60% of the 5HT, and 80% of the NE.

Alprostadil↗
PubMed1982

Rat brain monoamine levels related to behavioral assessment.

Randomly selected adult, male, Sprague-Dawley rats exhibit a range of behaviors in an open field. Exploration without defecation or urination is interpreted as stable behavior. On the basis of their open field behavior we selected the five most "emotional" and five most "stable" rats from two separate groups of thirty rats. Norepinephrine (NE), dopamine (DA), and serotonin (5HT) levels were determined in brains from these ten "emotional" and ten "stable" rats. The NE levels of "emotional" rats were elevated about 60 ng/g relative to the "stable" rats. There was no difference in DA levels, but there appeared to be a trend toward elevation of 5HT levels in the "emotional" rats. These findings directly support the hypothesis that elevated central nervous system norepinephrine levels may reflect a factor which contributes to emotionality in the rat, and suggest that brain norepinephrine levels may be a biochemical mechanism which influences performance as seen with the commonly used open field behavioral test of emotionality.

Animals↗