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Biomedical subjects

F L Powell

Publications and source records attributed to F L Powell.

At least 37 records · Page 2Linked to original sources
PubMed2000

Physiological effects of intermittent hypoxia.

Intermittent hypoxia (IH), or periodic exposure to hypoxia interrupted by return to normoxia or less hypoxic conditions, occurs in many circumstances. In high altitude mountaineering, IH is used to optimize acclimatization although laboratory studies have not generally revealed physiologically significant benefits. IH enhances athletic performance at sea level if blood oxygen capacity increases and the usual level of training is not decreased significantly. IH for high altitude workers who commute from low altitude homes is of considerable practical interest and the ideal commuting schedule for physical and mental performance is being studied. The effect of oxygen enrichment at altitude (i.e., intermittent normoxia on a background of chronic hypoxia) on human performance is under study also. Physiological mechanisms of IH, and specifically the differences between effects of IH and acute or chronic continuous hypoxia remains to be determined. Biomedical researchers are defining the molecular and cellular mechanisms for effects of hypoxia on the body in health and disease. A comparative approach may provide additional insight about the biological significance of these effects.

Acclimatization↗
PubMed2000

Nocturnal O2 enrichment of room air at high altitude increases daytime O2 saturation without changing control of ventilation.

In a randomized, double-blind study, 24 sea-level residents drove to 3,800-m altitude in 1 day, and then slept the first night in either ambient air or 24% oxygen, and the second night in the treatment that they did not receive on the first night. Oxygen enrichment, compared with ambient air, resulted in significantly fewer apneas, and significantly less time spent in periodic breathing during the night. The increase in SaO2 between evening and morning was significantly higher after sleeping in the oxygen-enriched atmosphere, compared with ambient air. However, this significant improvement in SaO2 did not persist into mid-day. The overnight treatment did not alter the ventilatory response to hypoxia or to carbon dioxide as measured the following morning. The results suggest that the elevation in SaO2 following overnight oxygen enrichment is probably not due to a change in the control of ventilation, but possibly to differences in subclinical lung pathology.

Adult↗
PubMed2000

Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine D(2) receptors.

We used genetically engineered D(2) receptor-deficient [D(2)-(-/-)] and wild-type [D(2)-(+/+)] mice to test the hypothesis that dopamine D(2) receptors modulate the ventilatory response to acute hypoxia [hypoxic ventilatory response (HVR)] and hypercapnia [hypercapnic ventilatory response (HCVR)] and time-dependent changes in ventilation during chronic hypoxia. HVR was independent of gender in D(2)-(+/+) mice and significantly greater in D(2)-(-/-) than in D(2)-(+/+) female mice. HCVR was significantly greater in female D(2)-(+/+) mice than in male D(2)-(+/+) and was greater in D(2)-(-/-) male mice than in D(2)-(+/+) male mice. Exposure to hypoxia for 2-8 days was studied in male mice only. D(2)-(+/+) mice showed time-dependent increases in "baseline" ventilation (inspired PO(2) = 214 Torr) and hypoxic stimulated ventilation (inspired PO(2) = 70 Torr) after 8 days of acclimatization to hypoxia, but D(2)-(-/-) mice did not. Hence, dopamine D(2) receptors modulate the acute HVR and HCVR in mice in a gender-specific manner and contribute to time-dependent changes in ventilation and the acute HVR during acclimatization to hypoxia.

Acclimatization↗
PubMed2000

Intermittent vs continuous hypoxia: effects on ventilation and erythropoiesis in humans.

OBJECTIVE: Recently, we showed that 5 days of normobaric intermittent hypoxia at rest (IH; 2 hours daily at 3,800 m simulated altitude; partial pressure of inspired oxygen 90 torr) can induce an increase in the isocapnic hypoxic ventilatory response (HVR) and blood reticulocyte count. The purpose of the present study was to compare these data with continuous exposure to the same hypoxic level. METHODS: Four of the same subjects were exposed, a year later, to 2 days of continuous hypoxia (CH), and 4 different subjects were exposed to 8 weeks of CH, both at the White Mountain Research Station (3,800 m altitude, barometric pressure approximately 489 torr). Inspired minute ventilation (VI), end-tidal partial pressure of carbon dioxide, arterial oxygen saturation (SaO2[sat]), hematocrit, and hemoglobin concentration were measured at different times during the continuous exposures. The HVR was expressed as the increase in V1 per 1% decrease in SaO2. RESULTS: The HVR showed no significant difference in the control values 1 year apart (IH, 0.06 +/- 0.03; CH2d (2 days' continuous hypoxia), 0.19 +/- 0.07 L x min(-1) x %sat(-1); means +/- SE), and the HVR values were similar after 2 days of IH compared to CH (0.42 +/- 0.26 and 0.51 +/- 0.22 L x min(-1) x %sat(-1), respectively). On the new subjects after 2 weeks of CH, the HVR showed a maximum increase, similar to the increase observed after only 5 days of IH, hemoglobin concentrations and hematocrit were significantly increased (45.0 +/- 2.7% vs 51.5 +/- 3.0% and 14.5 +/- 0.7 vs 17.2 +/- 1.0 g x dL(-1), respectively). The HVR did not change significantly from week 2 to 8 of CH, whereas hematological data were still increasing at the end of the 8 weeks. CONCLUSION: Changes in ventilatory oxygen sensitivity induced by IH and CH are similar in magnitude but occur with different time courses. The effects of IH on erythropoiesis are significant but fewer than on CH.

Acclimatization↗
PubMed1999

Chronic hypoxia enhances the phrenic nerve response to arterial chemoreceptor stimulation in anesthetized rats.

Chronic exposure to hypoxia results in a time-dependent increase in ventilation called ventilatory acclimatization to hypoxia. Increased O(2) sensitivity of arterial chemoreceptors contributes to ventilatory acclimatization to hypoxia, but other mechanisms have also been hypothesized. We designed this experiment to determine whether central nervous system processing of peripheral chemoreceptor input is affected by chronic hypoxic exposure. The carotid sinus nerve was stimulated supramaximally at different frequencies (0.5-20 Hz, 0.2-ms duration) during recording of phrenic nerve activity in two groups of anesthetized, ventilated, vagotomized rats. In the chronically hypoxic group (7 days at 80 Torr inspired PO(2)), phrenic burst frequency (f(R), bursts/min) was significantly higher than in the normoxic control group with carotid sinus nerve stimulation frequencies >5 Hz. In the chronically hypoxic group, peak amplitude of integrated phrenic nerve activity ( integral Phr, percent baseline) or change in integral Phr was significantly greater at stimulation frequencies between 5 and 17 Hz, and minute phrenic activity ( integral Phr x f(R)) was significantly greater at stimulation frequencies >5 Hz. These experiments show that chronic hypoxia facilitates the translation of arterial chemoreceptor afferent input to ventilatory efferent output through a mechanism in the central nervous system.

Acclimatization↗
PubMed1998

Hypoxic adaptation of the peptidergic innervation in the rat carotid body.

The abundance of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, and neuropeptide Y (NPY)-immunoreactive nerve fibers in the carotid body was compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). The immunoreactive fibers appeared as thin processes with many varicosities, and were distributed mainly around the vasculatures. In the normoxic control carotid body, NPY fibers were more numerous than VIP, CGRP, and SP fibers. In the chronically hypoxic rats, the carotid body was enlarged several fold, and the mean absolute number of VIP and NPY fibers was 3.88 and 2.22 times higher than in the normoxic carotid body, respectively, although that of SP and CGRP fibers was not changed. When expressed as density per unit area of the parenchyma, the density of SP and CGRP fibers in the chronically hypoxic carotid body decreased significantly to under 50%, the density of VIP fibers increased significantly 1.80 times, and the density of NPY fibers were unchanged. Immunoreactivity for four neuropeptides was not found in the glomus cells of normoxic or chronically hypoxic carotid bodies. These results suggest that altered peptidergic innervation of the chronically hypoxic carotid body is one feature of hypoxic adaptation. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia.

Adaptation, Physiological↗
PubMed1998

Time domains of the hypoxic ventilatory response.

The ventilatory response to hypoxia depends on the pattern and intensity of hypoxic exposure and involves several physiological mechanisms. These mechanisms differ in their effect (facilitation or depression) on different components of ventilation (tidal volume and frequency) and in their time course (seconds to years). Some mechanisms last long enough to affect future ventilatory responses to hypoxia, indicating 'memory' or functional plasticity in the ventilatory control system. A standard terminology is proposed to describe the different time domains of the hypoxic ventilatory response (HVR) and to promote integration of results from different experimental preparations and laboratories. In general, the neurophysiological and neurochemical basis for short time domains of the HVR (seconds and minutes) are understood better than longer time domains (days to years), primarily because short time domains are studied in the laboratory more easily. Understanding the mechanisms for different time domains of the HVR has important implications for both basic and clinical science.

Acclimatization↗
PubMed1998

Room oxygen enrichment improves sleep and subsequent day-time performance at high altitude.

We carried out a randomized, double-blind trial at 3800 m altitude to test whether a small degree of room oxygen enrichment at night improves sleep quality, and performance and well-being the following day. Eighteen sea-level residents drove from sea level to 3800 m in one day, and then slept one night in ambient air, and another night in 24% oxygen, the order being randomized. With oxygen enrichment the subjects had fewer apneas (P < 0.01) and spent less time in periodic breathing with apneas (P < 0.01) than when they slept in ambient air. Subjective assessments of sleep quality were also significantly improved. There was a lower acute mountain sickness score during the morning after oxygen-enriched sleep (P < 0.01) and a greater increase in arterial oxygen saturation from evening to morning (P < 0.05). The larger increases in arterial oxygen saturation from evening to morning suggest that the control of breathing may have been altered. Installing an oxygen-enriched room at high altitude is relatively simple and inexpensive, and shows promise for improving well-being of both commuters and residents.

Adult↗
PubMed1998

The respiratory effects of the cytokine regulating agent HP 228 alone and in combination with morphine in human volunteers.

HP 228 is a synthetic heptapeptide analog of alpha-MSH that attenuates the production and release of inflammatory cytokines. The purpose of this study was to define HP 228's effects, alone and in combination with morphine, on resting ventilation and the ventilatory response to hypoxia and hypercarbia. Six healthy nonsmoking young adult males completed the four-session experiment. Subjects first underwent an initial training session. During subsequent sessions, each subject was tested for the respiratory effects of intravenous HP 228 (30 microg/kg), morphine (0.15 mg/kg), or HP 228 (30 microg/kg) plus morphine (0.15 mg/kg) in a double-blind placebo-controlled randomized balanced within-subjects experimental design. Sessions began with baseline measurement of resting ventilation, oxygen consumption, the isocapnic hypoxic ventilatory response (HVR), and normoxic hypercapnic ventilatory response (HCVR). A second set of respiratory measurements were obtained 10 min after completion of HP 228 or placebo infusion. Morphine or placebo was then administered and ventilatory responses were determined 15 and 40 min postinfusion. HP 228 produced cutaneous flushing, but had no significant effect on respiration or hemodynamics. Morphine significantly decreased metabolism, resting ventilation, and hypoxic and hypercarbic ventilatory responsiveness, independent of prior HP 228 administration. A seventh subject experienced a significant cardiac arrhythmia upon exposure to hypoxia after receiving both HP 228 and morphine and was withdrawn from further study. In conclusion, in this early Phase I clinical trial, HP 228 was found to neither depress ventilation nor augment morphine-induced respiratory depression in healthy young males.

Adult↗
PubMed1996

Tst-1/Oct-6/SCIP regulates a unique step in peripheral myelination and is required for normal respiration.

The terminal differentiation of myelinating glia involves complex interactions that culminate in the formation of myelin. The POU domain transcription factor Tst-1/Oct-6/SCIP is expressed transiently during myelination, and we report here that it has a critical role in this developmental process. Deletion of the Tst-1/Oct-6/SCIP gene produces a severe defect in peripheral myelination by arresting Schwann cell maturation before axonal wrapping. Unexpectedly, the activation of major myelin-specific genes appears to be unaffected by the Tst-1/Oct-6/SCIP mutation, demonstrating that multiple, independently regulated events are required for terminal differentiation of Schwann cells. In addition, aberrant differentiation and migration of specific neurons in Tst-1/Oct-6/SCIP mutant homozygotes is associated with a fatal breathing defect, providing a model for investigating the regulation of pulmonary homeostasis.

Animals↗
PubMed1996

Distribution of substance P and calcitonin gene-related peptide immunoreactive nerve fibers in the trachea of chronically hypoxic rats.

The distribution of substance P and calcitonin gene-related peptide immunoreactive nerve fibers in the trachea was compared between normoxic and chronically hypoxic rats (at 380 mm Hg for 10 weeks). In the normoxic trachea, the immunoreactivity to either peptide was seen in the nerve fibers in four principal locations: a) within and b) under the ciliated epithelium, c) within the smooth muscle bundles in the posterior wall, and d) in the connective tissue and around blood vessels in the lamina propria and submucosa. These immunoreactive fibers within the epithelium and smooth muscle bundles, in the connective tissue, and around blood vessels were thin and displayed some varicosities, and those under the epithelium appeared as thick nerve bundles. When the distribution and density of immunoreactive fibers were compared between normoxic and chronically hypoxic tracheas, there was a difference in number of substance P and calcitonin gene-related peptide immunoreactive fibers penetrating into the epithelium, although there was no difference in the other three locations. The mean number of substance P and calcitonin gene-related peptide immunoreactive intraepithelial fibers per section of the chronically hypoxic trachea was significantly increased. Because substance P and calcitonin gene-related peptide are predominant signal peptides of primary sensory neurons, the increase of substance P and calcitonin gene-related peptide immunoreactive fibers suggests that altered airway reflexes may be a feature of hypoxic adaptation.

Animals↗
PubMed1995

Ventilation and pulmonary gas exchange during exercise in the savannah monitor lizard (Varanus exanthematicus).

During exercise, pulmonary gas exchange in reptiles was predicted to differ from that in mammals because of their less complex lung structure, which might reduce ventilation-perfusion heterogeneity (V/QL) at the expense of pulmonary diffusion limitation. To investigate this, the multiple inert gas elimination technique was used in six Varanus exanthematicus at rest and during maximal exercise. Trace amounts of six inert gases were infused into the external jugular vein and blood samples were collected from the pulmonary artery and the left atrium. Mixed expired gas samples and ventilatory and metabolic data were acquired. Indices of V/QL heterogeneity, calculated using a 50-compartment model, were low at rest (log standard deviation of perfusion distribution, logSDQ = 0.39) and increased significantly with exercise (logSDQ = 0.78). Oxygen diffusion limitation was apparent during exercise and was comparable to reported mammalian values. A molecular-mass-dependent limitation, suggesting limited intrapulmonary gas mixing, was evident only at rest. An increase in left atrial PO2 from 82mmHg at rest to 96 mmHg during exercise was associated with a corresponding decrease in PCO2. These data indicate adequacy of pulmonary ventilation and gas exchange for metabolic demands in exercising varanid lizards and suggest that less complex lung structures are not necessarily linked to increased pulmonary diffusion limitation.

Animals↗
PubMed1994

Susceptibility of human LDL to oxidative modification. Effects of variations in beta-carotene concentration and oxygen tension.

Epidemiological studies suggest that beta-carotene supplementation may decrease atherosclerotic events. Because beta-carotene is transported in low-density lipoprotein (LDL), one mechanism by which this protective effect may occur is through direct inhibition of LDL oxidation. Addition of beta-carotene to LDL in vitro inhibits the susceptibility of LDL to oxidation. In contrast, we have shown that feeding large doses of beta-carotene results in beta-carotene-enriched plasma LDL (16- to 35-fold), but such LDL does not show increased resistance to oxidation. Potential criticisms of our initial study relate to the unique antioxidant properties of beta-carotene. Beta-Carotene provides better quenching of some free radicals, such as singlet oxygen, than others. Additionally, since beta-carotene can easily autooxidize, forming metabolites that can also generate free radicals, it has been argued that at sufficient concentrations in vivo the antioxidant effect of beta-carotene may be diminished. It has thus been suggested that in our initial study we may have failed to properly assess the unique antioxidant effects of beta-carotene by our selection of oxidizing conditions and/or failed to achieve antioxidant activity because of excessive enrichment of LDL with beta-carotene. We now report the effects of feeding lower doses of beta-carotene on the susceptibility of LDL to oxidation and test whether any antioxidant activity of beta-carotene can be detected when different modes of initiating oxidation are used. Because the antioxidant activity of beta-carotene is reputedly most pronounced in low-oxygen environments, we also investigated its effect on LDL oxidation under conditions of reduced oxygen tension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Ultrastructure of the glomus cells in the carotid body of chronically hypoxic rats: with special reference to the similarity of amphibian glomus cells.

The ultrastructural characteristics of the glomus cells in the rat carotid body exposed to extremely long-term hypoxia (10-12 weeks) were investigated. The glomus cells could be classified into four distinct types according to the shape of dense-cored vesicles in the glomus cell cytoplasm: 1) small vesicle cells (SVCs, 50 nm in mean diameter), 2) large vesicle cells (LVCs, 80 nm in mean diameter), 3) dilated eccentric vesicle cells (EVCs, 400-800 nm in diameter), and 4) mixed vesicle cells (MVCs, large and eccentric vesicles). Many clusters of glomus cells were found to contain all four categories of cell types. The appearance of EVCs was a unique and common characteristic of glomus cells in this long-term hypoxia model. We also noted other ultrastructural features with chronic hypoxia which are characteristic of the amphibian carotid labyrinth glomus cells: 1) incomplete covering of glomus cells with the supporting cell missing over a wide area, 2) long thin cytoplasmic projections in the intervascular stroma, and 3) intimate apposition of the glomus cells and pericytes (g-p connection), endothelial cells (g-e connection), plasma cells, and fibrocytes. Because arterial PO2 is generally low in amphibia, these may be general features of hypoxic adaptation and facilitate both uptake of oxygen from blood and release of catecholamine into the blood. The g-p and g-e connections may take part in the regulation of the microcirculation in the enlarged carotid body.

Amphibians↗
PubMed1993

Diffusion limitation in comparative models of gas exchange.

Piiper and Scheid (Resp. Physiol. 23: 209-221, 1975) compared different models of external gas exchange with performance indices defined as functions of ventilatory/perfusive and diffusive/perfusive conductance ratios (Gvent/Gperf and Gdiff/Gperf, where Gdiff is diffusing capacity). We expanded their analysis to include: (1) delta pD, the average partial pressure gradient driving diffusion across the exchange barrier, normalized to the maximum gradient available (Pi-Pv), and (2) Jdiff, the sensitivity of total conductance to changes in Gdiff, where total conductance is the ratio of gas flux to the maximum gradient [GTOT = M/(Pi-Pv)]. Although the counter-current model is most efficient, it is more sensitive than cross-current or ventilated pool models to changes in Gdiff. For given Gvent, Gperf and Pi-Pv, maximum GTOT may not be achieved in the counter-current model until Gdiff is over ten-fold greater than that necessary for maximum GTOT in the other models. Experimental data also shows greater Jdiff and diffusion limitation in fish than in birds or mammals. We conclude that counter-current O2 exchange cannot approach ideal levels as closely as the ventilated pool or cross-current models in nature.

Animals↗
PubMed1993

Effect of chronic hypoxia on hypoxic ventilatory response in awake rats.

We compared the hypoxic ventilatory response (HVR) of two groups of unrestrained awake male rats (300-550 g): those acclimatized to hypoxia > 7 wk at simulated altitude (380 Torr, n = 12) and sea level controls (n = 8). Chronic catheters were placed in the iliac artery and vein 3-7 days before study. An "on-line" system was used to measure arterial PO2 and PCO2. Arterial blood was drawn via a roller pump past O2 and CO2 electrodes and returned to the vein. Batch samples were taken before and after HVR measurements for calibrating and determining arterial pH and hematocrit. Inspired ventilation, tidal volume, and respiratory frequency were measured with barometric pressure plethysmography at several levels of inspired O2 fraction (0.08-0.30) maintained for 15 min. For isocapnic HVR, inspired CO2 fraction was increased as necessary to maintain arterial PCO2 at the hyperoxic level. In both groups, poikilocapnic HVRs (inspired CO2 fraction = 0) were significantly less than isocapnic HVRs. Isocapnic HVRs were significantly greater in hypoxia-acclimatized (2,783 +/- 233 ml.min-1.kg-1) than in sea level control rats (1,826 +/- 106 ml.min-1.kg-1), mainly due to a significant increase in tidal volume (P < 0.05). In conclusion, relieving hypocapnia in hypoxia, by maintaining isocapnia, reveals a significant increase in the ventilatory response to arterial PO2 in awake rats with chronic hypoxia.

Acclimatization↗