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Biomedical subjects

F L Powell

Publications and source records attributed to F L Powell.

At least 19 recordsLinked to original sources
PubMed2005

Spike firing allometry in avian intrapulmonary chemoreceptors: matching neural code to body size.

Biological rates in small animals are usually higher than those in large animals, yet the maximal rate of action potential (spike) generation in sensory neurons encoding rate functions is similar in all animals, due to the conserved genetics of voltage-gated ion channels. Therefore, sensory signals that vary at rates approaching maximal spike generation rate, as might occur in animals of diminished body size, may require specialized spike coding to convey this information. To test whether spike coding scales allometrically in sensory neurons monitoring signals that change frequency with body size, we recorded action potentials from 70 avian intrapulmonary chemoreceptors (IPC), respiratory neurons that detect lung CO2 changes during breathing, in five different avian species ranging in size from body mass Mb=0.045 kg (lovebirds) to 5.23 kg (geese). Since breathing frequency scales approximately to Mb-1/4 (higher in small birds, lower in large birds), we reasoned that IPC discharge frequencies may also scale to maintain spike information transmission within each breath. We found that phasic action potential discharge pattern, as quantified by the peak discharge rate and the magnitude of spike frequency adaptation, scaled between Mb-0.22 and Mb-0.26, like breathing rate (P<0.05). Previously published values of peak discharge rate in IPC also fit this allometric relationship. We suggest that mass-dependent scaling of neural coding may be necessary for preserving information transmission with decreasing body size.

Action Potentials↗
PubMed2003

Dopaminergic mechanisms of neural plasticity in respiratory control: transgenic approaches.

Data supporting the hypothesis that dopamine-2 receptors (D(2)-R) contribute to time-dependent changes in the hypoxic ventilatory response (HVR) during acclimatization to hypoxia are briefly reviewed. Previous experiments with transgenic animals (D(2)-R 'knockout' mice) support this hypothesis (J. Appl. Physiol. 89 (2000) 1142). However, those experiments could not determine (1) if D(2)-R in the carotid body, the CNS, or both were involved, or (2) if D(2)-R were necessary during the acclimatization to hypoxia versus some time prior to chronic hypoxia, e.g. during a critical period of development. Additional experiments on C57BL/6J mice support the idea that D(2)-R are critical during the period of exposure to hypoxia for normal ventilatory acclimatization. D(2)-R in carotid body chemoreceptors predominate under control conditions to inhibit normoxic ventilation, but excitatory effects of D(2)-R, presumably in the CNS, predominate after acclimatization to hypoxia. The inhibitory effects of D(2)-R in the carotid body are reset to operate primarily under hypoxic conditions in acclimatized rats, thereby optimizing O(2)-sensitivity.

Acclimatization↗
PubMed2003

Open-flow plethysmography with pressure-decay compensation.

Whole-body plethysmography is widely used to measure ventilation in awake, unrestrained animals. However, the explicit solution for volumetric analysis of the plethysmograph signal depends upon a closed system, which limits experimental design. Although often used, open-flow plethysmography is complicated by the time-decay of pressure signals generated in the open chamber (e.g. equivalent volume displacements will yield different pressure pulse magnitudes depending upon the rate of application, dP/dt). This problem may be alleviated by first characterizing the time rate of pressure-decay, dP(k)/dt, as a function of pressure magnitude, P, in the plethysmograph, dP(k(P))/dt. Then for each point P(t) in the original signal, subtract the corresponding dP(k(P))(t)/dt from each dP(t)/dt of the original signal to determine the decay-compensated derivative for that point, dP*(t)/dt, and then numerically integrate dP*(t)/dt to generate a pressure-decay compensated signal. The result is a 'virtual closed plethysmograph' trace that enables confident quantitative determination of ventilatory events and volumes with the full advantage of an open-flow plethysmograph.

Animals↗
PubMed2002

Ventilation-perfusion inequality during normoxic and hypoxic exercise in the emu.

Many avian species exhibit an extraordinary ability to exercise under hypoxic condition compared with mammals, and more efficient pulmonary O(2) transport has been hypothesized to contribute to this avian advantage. We studied six emus (Dromaius novaehollandaie, 4-6 mo old, 25-40 kg) at rest and during treadmill exercise in normoxia and hypoxia (inspired O(2) fraction approximately 0.13). The multiple inert gas elimination technique was used to measure ventilation-perfusion (V/Q) distribution of the lung and calculate cardiac output and parabronchial ventilation. In both normoxia and hypoxia, exercise increased arterial Po(2) and decreased arterial Pco(2), reflecting hyperventilation, whereas pH remained unchanged. The V/Q distribution was unimodal, with a log standard deviation of perfusion distribution = 0.60 +/- 0.06 at rest; this did not change significantly with either exercise or hypoxia. Intrapulmonary shunt was <1% of the cardiac output in all conditions. CO(2) elimination was enhanced by hypoxia and exercise, but O(2) exchange was not affected by exercise in normoxia or hypoxia. The stability of V/Q matching under conditions of hypoxia and exercise may be advantageous for birds flying at altitude.

Altitude↗
PubMed2001

Common themes of adaptation to hypoxia. Insights from comparative physiology.

Many vertebrate animals have superior tolerance to environmental hypoxia compared to humans. For example, turtles tolerate an environment of 100% N2 for several hours, without apparent ill effect. This hypoxia tolerance is not limited to heterotherms, as some species of marine mammals, such as the northern elephant seal, may voluntarily dive for periods of up to 2 hours. Torpid bats exhibit prolonged periods of apnea and passive diffusion of oxygen down their trachea through an open glottis supplies a significant amount of the oxygen uptake. The Ruppell's griffon holds the known avian record of flight at 11,278 m, and other birds regularly migrate at altitudes over 8000m. These animals exhibit diverse adaptations for tolerating their hypoxic environment, many of which are poorly understood. Some of theses strategies include 1) the ability to lower metabolic rate when exposed to hypoxia 2) the ability to recruit alternate biochemical pathways for energy production 3) a left shifted oxy-hemoglobin dissociation curve 4) more efficient pulmonary gas exchange 5) the ability to alter blood flow distribution under hypoxic stress. Although there are common themes of animal adaptation to hypoxic stress, many animal solutions are unique.

Acclimatization↗
PubMed2001

Ventilatory response to 2-h sustained hypoxia in humans.

We used two protocols to determine if hypoxic ventilatory decline (HVD) involves changes in slope and/or intercept of the isocapnic HVR (hypoxic ventilatory response, expressed as the increase in VI per percentage decrease in SaO2). Isocapnia was defined as 1.5 mmHg above hyperoxic PET(CO2). HVD was recorded in protocol I during two sequential 25 min exposures to isocapnic hypoxia (85 and 75% SaO2, n=7) and in protocol II during 14 min of isocapnic hypoxia (90% SaO2, FIO2=0.13, n=15), extended to 2 h of hypoxia with CO2-uncontrolled in eight subjects. HVR was measured by the step reduction to sequentially lower levels of SaO2 in protocol I and by 3 min steps to 80% SaO2 at 8, 14 and 120 min in protocol II. The intercept of the HVR (VI predicted at SaO2=100%) decreased after 14 and 25 min in both protocols (P<0.05). Changes in slope were observed only in protocol I at SaO2=75%, suggesting that the slope of the HVR is more sensitive to depth than duration of hypoxic exposure. After 2 h of hypoxia the HVR intercept returned toward control value (P<0.05) with still no significant changes in the HVR slope. We conclude that HVD in humans involves a decrease in hyperoxic ventilatory drive that can occur without significant change in slope of the HVR. The partial reversal of the HVD after 2 h of hypoxia may reflect some components of ventilatory acclimatization to hypoxia.

Adult↗
PubMed2001

Time domains of the hypoxic ventilatory response in awake ducks: episodic and continuous hypoxia.

Time-dependent ventilatory responses to episodic and continuous isocapnic hypoxia were measured in unidirectionally ventilated, awake ducks. Three protocols were used: (1) ten 3-min episodes of moderate hypoxia (10% O(2)) with 5-min normoxic intervals; (2) three 3-min episodes of severe hypoxia (8% O(2)) with 5-min normoxic intervals; and (3) 30-min of continuous moderate hypoxia. Ventilation (V(I)) increased immediately within a hypoxic episode (acute response), followed by a further slow rise in V(I) (short-term potentiation). The peak V(T) response increased from the first to second moderate hypoxic episode (progressive augmentation), but was unchanged thereafter. During normoxic intervals, V(I) increased progressively (56% following the tenth episode; long term facilitation). Time-dependent changes were not observed during or following 30-min of continuous hypoxia. Although several time-dependent ventilatory responses to episodic hypoxia are observed in awake ducks, they are relatively small and biased towards facilitation versus inhibitory mechanisms.

Animals↗
PubMed2001

Nocturnal oxygen enrichment of room air at 3800 meter altitude improves sleep architecture.

Sleep is known to be impaired at high altitude, and this may be a factor contributing to reduced work efficiency, general malaise, and the development of acute mountain sickness (AMS). Nocturnal room oxygen enrichment at 3800 m has been shown to reduce the time spent in periodic breathing and the number of apneas, to improve subjective quality of sleep, and to reduce the AMS score. The present study was designed to evaluate the effect of oxygen enrichment to 24% at 3800 m (lowering the equivalent altitude to 2800 m) on sleep architecture. Full polysomnography and actigraphy were performed on 12 subjects who ascended in 1 day to 3800 m and slept in a specially constructed room that allowed oxygen enrichment or ambient air conditions in a randomized, crossover, double-blind study. The results showed that subjects spent a significantly greater percentage of time in deep sleep (stages III and IV combined, or slow wave sleep) with oxygen enrichment versus ambient air (17.2 +/- 10.0% and 13.9 +/- 6.7%, respectively; p < 0.05 in paired analysis). No differences between treatments were seen with subjective assessments of sleep quality or with subject's assessment of the extent to which they suffered from AMS. This study provides further objective evidence of improved sleep as a result of oxygen enrichment at 3800 m and suggests that alleviating hypoxia may improve sleep quality.

Adult↗
PubMed2001

Ventilatory long-term facilitation in unanesthetized rats.

We tested the hypothesis that unanesthetized rats exhibit ventilatory long-term facilitation (LTF) after intermittent, but not continuous, hypoxia. Minute ventilation (VE) and carbon dioxide production (VCO(2)) were measured in unanesthetized, unrestrained male Sprague-Dawley rats via barometric plethysmography before, during, and after exposure to continuous or intermittent hypoxia. Hypoxia was either isocapnic [inspired O(2) fraction (FI(O(2))) = 0.08--0.09 and inspired CO(2) fraction (FI(CO(2))) = 0.04] or poikilocapnic (FI(O(2)) = 0.11 and FI(CO(2)) = 0.00). Sixty minutes after intermittent hypoxia, VE or VE/VCO(2) was significantly greater than baseline in both isocapnic and poikilocapnic conditions. In contrast, 60 min after continuous hypoxia, VE and VE/VCO(2) were not significantly different from baseline values. These data demonstrate ventilatory LTF after intermittent hypoxia in unanesthetized rats. Ventilatory LTF appeared similar in its magnitude (after accounting for CO(2) feedback), time course, and dependence on intermittent hypoxia to phrenic LTF previously observed in anesthetized, vagotomized, paralyzed rats.

Animals↗
PubMed2000

Time-dependent changes in dopamine D(2)-receptor mRNA in the arterial chemoreflex pathway with chronic hypoxia.

The hypoxic ventilatory response (HVR) can be modulated by dopamine D(2)-receptors (D(2)-R) in both the carotid body arterial chemoreceptors and the nucleus tractus solitarius (NTS), the primary synapse site of carotid body afferents. We hypothesized that chronic hypoxia alters D(2)-R gene expression to initiate changes in D(2)-R modulation of the HVR and enhance ventilatory acclimatization to hypoxia. Thus, we used a competitive reverse transcription-polymerase chain reaction (RT-PCR) method to quantify changes in D(2)-R mRNA levels in the rat carotid body and NTS after 0, 6, 12, 24, 48, or 168 h of hypobaric hypoxia (P(IO(2))=80 Torr). In the rostral NTS, hypoxia significantly increased D(2)-R mRNA at all time points. In the caudal NTS, D(2)-R mRNA levels initially increased in response to hypoxia and then significantly decreased to 71+/-5% and 71+/-6% of control after 48 and 168 h of hypoxia, respectively. In the carotid body, D(2)-R mRNA levels significantly decreased to 59+/-2% of control after 48 h of hypoxia; however, they significantly increased to 274+/-22% of control after 168 h. These results suggest that changes in D(2)-R mRNA in the arterial chemoreflex pathway and corresponding changes at the protein and signaling levels may contribute to the time-dependent changes in ventilation observed with chronic hypoxia. Specifically, decreased carotid body inhibition by D(2)-R could increase the HVR after 2 days of hypoxia.

Animals↗
PubMed2000

Chronic hypoxia induces changes in the central nervous system processing of arterial chemoreceptor input.

Chronic hypoxia increases the hypoxic ventilatory response (HVR) in awake rats and the phrenic nerve response to carotid sinus nerve stimulation in anesthetized rats. An increased O2 sensitivity of the arterial chemoreceptors contributes to the increase in the HVR, but changes in the CNS processing of afferent information from arterial chemoreceptors are also involved. Adult male Sprague-Dawley rats were exposed to 0-7 days of hypobaric hypoxia (PIO2 = 80 Torr). Ventilation was measured in rats exposed to 0, 2 and 7 days of hypoxia using whole-body plethysmography. Ventilation increased after 2 days and remained elevated after 7 days of hypoxia. Following dopamine D2 receptor (D2-R) blockade in the CNS, frequency significantly decreased after 0 and 7 days of hypoxia, but did not change significantly after 2 days of hypoxia. In anesthetized rats, the phrenic nerve response to carotid sinus nerve stimulation was reduced following systemic D2-R blockade in control rats and those exposed to 7 days of hypoxia. After 2 days of hypoxia, there was no effect of blocking systemic D2-R. To determine whether changes in D2-R mRNA precede physiological changes, competitive RT-PCR was used to quantify D2-R mRNA in micropunches from the nucleus tractus solitarius (NTS) in normoxic and chronically hypoxic rats. In hypoxia, D2-R mRNA in the caudal NTS initially increased (6-12 hours) and then decreased below control levels (24 hours-7 days). These results show that chronic hypoxia causes time-dependent changes in D2-R that could result in changes in the ventilatory response to hypoxia.

Acclimatization↗
PubMed2000

Central nervous system mechanisms of ventilatory acclimatization to hypoxia.

Ventilatory acclimatization to hypoxia is the time-dependent increase in ventilation that occurs with chronic exposure to hypoxia. Despite decades of research, the physiological mechanisms that increase the hypoxic ventilatory response during chronic hypoxia are not well understood. This review focuses on adaptations within the central nervous system (CNS) that increase the hypoxic ventilatory response. Although an increase in CNS responsiveness had been proposed many years ago, only recently has strong experimental evidence been provided for an increase in the CNS gain in the rat, which has proved to be a good model of VAH in humans. Within the CNS, several neuroanatomical sites could be involved as well as changes in various neurotransmitters, neuromodulators or signalling mechanisms within any of those sites. Lastly, adaptations within the CNS could involve both direct effects of decreased P(O(2)) and indirect effects of increased afferent nerve activity due to chronic stimulation of the peripheral arterial chemoreceptors.

Acclimatization↗
PubMed2000

Effects of intermittent hypoxia on the isocapnic hypoxic ventilatory response and erythropoiesis in humans.

Isocapnic hypoxic ventilatory response (HVR) and hematological variables were measured in nine adult males (age: 29.3+/-3.4) exposed to normobaric intermittent hypoxia (IH, 2 h daily at FI(O(2))=0.13, equivalent to 3800 m altitude) for 12 days. Mean HVR significantly increased during IH, however, after reaching a peak on Day 5 (0.79+/-0.12 vs. 0.27+/-0.11 L.min(-1).%(-1) on Day 1, P<0.05), it progressively decreased toward a lower value (0.46+/-0.16 L min(-1) x %(-1) on Day 12). In contrast, the subjects showed no changes in the ventilatory data and arterial O(2)-saturation in normoxia or poikilocapnic hypoxia (PET(CO(2)) uncontrolled). Hematocrit and hemoglobin concentration did not change, but the reticulocyte count increased by Day 5 (P<0.01). Our results suggest that moderate intermittent hypoxia induces changes in ventilatory O(2)-sensitivity and triggers the hematological acclimatization by increasing the percentage of reticulocytes in the blood. Normal ventilatory acclimatization to hypoxia was, however, not observed and the mechanisms involved in the biphasic changes in HVR we observed remain to be determined.

Adult↗
PubMed2000

Measuring ventilatory acclimatization to hypoxia: comparative aspects.

Acclimatization to hypoxia increases the hypoxic ventilatory response (HVR) in mammals. The literature on humans shows that several protocols can quantify this increase in HVR if isocapnia is maintained, regardless of the exact level of Pa(CO(2)). In rats, the isocapnic HVR also increases with chronic hypoxia and this cannot be explained by a non-specific effect of increased ventilatory drive on the HVR. Changes in arterial pH are predicted to increase the HVR during chronic hypoxia in rats but this has not been quantified. Limitations in determining mechanisms of change in the HVR from reflex experiments are discussed. Chronic hypoxia changes some, but not all, indices of ventilatory motor output that are useful for normalization between experiments on anesthetized rats. Finally, ducks also show time-dependent increases in ventilation during chronic hypoxia and birds provide a good experimental model to study reflex interactions. However, reflexes from intrapulmonary CO(2) chemoreceptors can complicate the measurement of changes in the isocapnic HVR during chronic hypoxia in birds.

Animals↗
PubMed2000

Changes in dopamine D(2)-receptor modulation of the hypoxic ventilatory response with chronic hypoxia.

Modulation of the hypoxic ventilatory response (HVR) by dopamine D(2)-receptors (D(2)-R) in the carotid body (CB) and central nervous system (CNS) are hypothesized to contribute to ventilatory acclimatization to hypoxia. We tested this with blockade of D(2)-R in the CB or CNS in conscious rats after 0, 2 and 8 days of hypoxia. On day 0, CB D(2)-R blockade significantly increased VI and frequency (fR) in hyperoxia (FI(O(2))=0.30), but not hypoxia (FI(O(2))=0.10). CNS D(2)-R blockade significantly decreased fR in hypoxia only. On day 2, neither CB nor CNS D(2)-R blockade affected VI or fR. On day 8, CB D(2)-R blockade significantly increased hypoxic VI and fR. CNS D(2)-R blockade significantly decreased hypoxic VI and fR. CB and CNS D(2)-R modulation of the HVR decreased after 2 days of hypoxia, but reappeared after 8 days. Changes in the opposing effects of CB and CNS D(2)-R on the HVR during chronic hypoxia cannot completely explain ventilatory acclimatization in rats.

Animals↗
PubMed2000

Six percent oxygen enrichment of room air at simulated 5,000 m altitude improves neuropsychological function.

Cognitive and motor function are known to deteriorate with the hypoxia accompanying high altitude, posing a substantial challenge to the efficient operation of high altitude industrial and scientific projects. To evaluate the effectiveness of enriching room air oxygen by 6% at 5,000 m altitude in ameliorating such deficits, 24 unacclimatized subjects (16 males, 8 females; mean age 37.8, range 20 to 47) underwent neuropsychological testing in a specially designed facility at 3,800 m that can simulate an ambient 5,000 m atmosphere and 6% enrichment at 5,000 m. Each subject was tested in both conditions in a randomized, double-blinded fashion. The 2-h test battery of 16 tasks assessed various aspects of motor and cognitive performance. Compared with simulated breathing air at 5,000 m, oxygen enrichment resulted in higher arterial oxygen saturations (93.0 vs. 81.6%), quicker reaction times, improved hand-eye coordination, and more positive sense of well-being (on 6 of 16 scales), each significant at the p < 0.05 level. Other aspects of neuropsychological function were not significantly improved by 6% additional oxygen.

Adult↗