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Biomedical subjects

G Bowes

Publications and source records attributed to G Bowes.

At least 109 records · Page 6Linked to original sources

Impaired detection of added inspiratory resistance in patients with obstructive sleep apnea.

The ability to detect added inspiratory flow-resistive loads during wakefulness was examined in 5 men with laboratory-documented obstructive sleep apnea. The patients were eucapnic, and standard measurements of lung volumes and flow rates were within the normal range. The patients breathed through a circuit, to which each of 5 flow resistances of 0.12 to 5.5 cm H2O/L/s was added at 20- to 30-s intervals for 1 inspiration, following a cue. Each resistance was presented 10 times in random sequence, and the percentage of trials in which each load was detected by the patient was calculated. The threshold level of load detection, defined as the change in resistance that could be detected 50% of the time, was higher in the patients (2.37 +/- 0.41 cmH2O/L/s, mean +/- SE) than in 9 healthy subjects (0.65 +/- 0.08; p less than 0.001), and this difference persisted when the threshold load was corrected for background resistance (1.05 +/- 0.11 versus 0.45 +/- 0.07; p less than 0.001). In addition, the ventilatory response to hypercapnia was less in the patients (1.82 +/- 0.22 L/min/mm Hg) than in the normal subjects (3.87 +/- 0.40; p less than 0.005), and there was a significant negative correlation (r = 0.97; p less than 0.001) between the load detection threshold and the ventilatory response to CO2. The results add to the developing concept that subtle defects in respiratory control can be demonstrated even during wakefulness in eucapnic patients with obstructive sleep apnea.

Adult↗

Arousal responses to chemical stimuli during sleep.

Arousal from sleep is an important component of any co-ordinated response to an external stimulus. Respiratory stimuli imposed during sleep are capable of eliciting arousal responses as well as the classic ventilatory responses Considerable survival advantage may result as a consequence of intact arousal mechanisms. Developmental studies of arousal responses to respiratory stimuli are lacking. Arousal responses to chemoreceptor stimuli have been examined in adult tracheotomized dogs, both before and following bilateral surgical denervation of the carotid bodies. Prior to denervation of the carotid bodies arousal in response to isocapnic progressive hypoxia occurred at an arterial oxygen saturation (SaO2) of 83% during slow-wave sleep and 70% in rapid-eye-movement sleep. Airway occlusion induced arousal from Slow-wave-sleep at SaO2 of 88% and from rapid-eye-movement sleep at SaO2 of 84%. Following denervation of the carotid bodies, arousal failed to occur in response to either progressive hypoxia or airway occlusion despite desaturation to 60% in Slow-wave sleep and 50% in rapid-eye-movement-sleep, at which level experiments were arbitrarily terminated. The effect of sleep fragmentation on arousal responses of sleeping dogs to chemoreceptor stimuli has also been studied. A marked impairment of both hypoxic and hypercapnic arousal was produced by sleep fragmentation. The consequences of interfering with arousal mechanisms in experimental animals indicates the considerable potential for similar dysfunction in man to contribute to the pathophysiology of the clinical syndromes of obstructive sleep apnoea and sudden infant death.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗

Two photosynthetic mechanisms mediating the low photorespiratory state in submersed aquatic angiosperms.

The submersed angiosperms Myriophyllum spicatum L. and Hydrilla verticillata (L.f.) Royal exhibited different photosynthetic pulse-chase labeling patterns. In Hydrilla, over 50% of the (14)C was initially in malate and aspartate, but the fate of the malate depended upon the photorespiratory state of the plant. In low photorespiration Hydrilla, malate label decreased rapidly during an unlabeled chase, whereas labeling of sucrose and starch increased. In contrast, for high photorespiration Hydrilla, malate labeling continued to increase during a 2-hour chase. Thus, malate formation occurs in both photorespiratory states, but reduced photorespiration results when this malate is utilized in the light. Unlike Hydrilla, in low photorespiration Myriophyllum, (14)C incorporation was via the Calvin cycle, and less than 10% was in C(4) acids.Ethoxyzolamide, a carbonic anhydrase inhibitor and a repressor of the low photorespiratory state, increased the label in glycolate, glycine, and serine of Myriophyllum. Isonicotinic acid hydrazide increased glycine labeling of low photorespiration Myriophyllum from 14 to 25%, and from 12 to 48% with high photorespiration plants. Similar trends were observed with Hydrilla. Increasing O(2) increased the per cent [(14)C]glycine and the O(2) inhibition of photosynthesis in Myriophyllum. In low photorespiration Myriophyllum, glycine labeling and O(2) inhibition of photosynthesis were independent of the CO(2) level, but in high photorespiration plants the O(2) inhibition was competitively decreased by CO(2). Thus, in low but not high photorespiration plants, glycine labeling and O(2) inhibition appeared to be uncoupled from the external [O(2)]/[CO(2)] ratio.These data indicate that the low photorespiratory states of Hydrilla and Myriophyllum are mediated by different mechanisms, the former being C(4)-like, while the latter resembles that of low CO(2)-grown algae. Both may require carbonic anhydrase to enhance the use of inorganic carbon for reducing photorespiration.

Journal Article↗

Effects of Light and Elevated Atmospheric CO(2) on the Ribulose Bisphosphate Carboxylase Activity and Ribulose Bisphosphate Level of Soybean Leaves.

Soybean (Glycine max L. Merr. cv Bragg) was grown throughout its life cycle at 330, 450, and 800 microliters CO(2) per liter in outdoor controlled-environment chambers under solar irradiance. Leaf ribulose-1,5-bisphosphate carboxylase (RuBPCase) activities and ribulose-1,5-bisphosphate (RuBP) levels were measured at selected times after planting. Growth under the high CO(2) levels reduced the extractable RuBPCase activity by up to 22%, but increased the daytime RuBP levels by up to 20%.Diurnal measurements of RuBPCase (expressed in micromoles CO(2) per milligram chlorophyll per hour) showed that the enzyme values were low (230) when sampled before sunrise, even when activated in vitro with saturating HCO(3) (-) and Mg(2+), but increased to 590 during the day as the solar quantum irradiance (photosynthetically active radiation or PAR, in micromoles per square meter per second) rose to 600. The nonactivated RuBPCase values, which averaged 20% lower than the corresponding HCO(3) (-) and Mg(2+)-activated values, increased in a similar manner with increasing solar PAR. The per cent RuBPCase activation (the ratio of nonactivated to maximum-activated values) increased from 40% before dawn to 80% during the day. Leaf RuBP levels (expressed in nanomoles per milligram chlorophyll) were close to zero before sunrise but increased to a maximum of 220 as the solar PAR rose beyond 1200. In a chamber kept dark throughout the morning, leaf RuBPCase activities and RuBP levels remained at the predawn values. Upon removal of the cover at noon, the HCO(3) (-) and Mg(2+)-activated RuBPCase values and the RuBP levels rose to 465 and 122, respectively, after only 5 minutes of leaf exposure to solar PAR at 1500.These results indicate that, in soybean leaves, light may exert a regulatory effect on extractable RuBPCase in addition to the well-established activation by CO(2) and Mg(2+).

Journal Article↗

Carotid chemoreceptor regulation of expiratory duration.

We studied the effect of an experimentally augmented breath on the duration of expiration (TE) to test the hypothesis that within-breath reductions in alveolar partial pressure of CO2 (PACO2) delay the onset of the subsequent inspiration through a carotid chemoreceptor mechanism. Studies were performed in five carotid body intact (CBI) and three carotid body denervated (CBD) dogs during quiet wakefulness and nonrapid-eye-movement sleep. The vagus nerves were blocked in order to abolish vagal mechanisms capable of modulating TE. In CBI dogs, mechanically augmented breaths [mean tidal volume (VT), 149% of control] induced a mean decrease in PACO2 of 3.3 Torr and prolonged TE by 2.21 s to 127% of control (P less than 0.001). In contrast, in CBD dogs augmented breaths of comparable magnitude failed to change TE. Spontaneous sighs in fully intact dogs (mean VT, 369% of control) produced marked prolongation of TE (to 429% of control). In CBI dogs, there was a direct relationship between VT and the resulting TE across all experimental conditions (control, vagal blockade, augmented breaths, spontaneous sighs), whereas in CBD dogs, changes in VT failed to alter TE. The results indicate that the carotid bodies are able to induce within-breath alterations in TE and that such a mechanism can account for the prolongation of TE by vagal blockade and by spontaneous sighs.

Animals↗

Ventilatory responses to inspiratory flow-resistive loads in awake and sleeping dogs.

We studied ventilatory responses to inspiratory flow-resistive loads in six trained dogs, during quiet wakefulness and non-rapid-eye-movement (NREM) sleep. During studies dogs lay quietly in a lateral position and breathed through an endotracheal tube inserted via a chronic tracheostomy. Linear resistances of 6, 10, 19, and 31 cmH2O X l-1 X s were applied during inspiration for only a single breath to assess the immediate ventilatory response. The highest resistance was also applied for five successive breaths to assess the progressive ventilatory response. Ventilatory responses to hyperoxic progressive hypercapnia were also examined, with and without flow-resistive loading. During loading the maintenance of constant states of quiet wakefulness and NREM sleep was confirmed by electroencephalographic monitoring. Ventilation decreased on the first loaded breath and returned to control in a stepwise manner by the fifth loaded breath. No state-related differences were observed in either the immediate or progressive ventilatory responses. During CO2 rebreathing, the slope of the ventilatory response to CO2 was reduced by loading, with the reduction in slope (as percent of control) greater in the NREM state. We therefore conclude that in the dog immediate and progressive ventilatory responses to resistive loads are unaffected by NREM sleep, whereas the decrease in ventilatory response to CO2 resulting from loading tends to be greater in NREM sleep than in quiet wakefulness.

Animals↗

Increased arterial pressure variability after arterial baroreceptor denervation in fetal lambs.

Baroreceptor reflexes can be demonstrated during fetal life, but whether baroreceptors normally regulate fetal arterial pressure is unknown. This problem was addressed directly by measuring arterial pressure and analyzing its variation in eight unanesthetized fetal lambs throughout the last third of gestation, and comparing these data with similar measurements made in seven fetal lambs with denervated arterial baroreceptors. Measurements were made at 5-minute intervals over 24 hours in a total of thirty-three experiments. The coefficient of variation of mean arterial pressure (standard deviation of mean arterial pressure/mean value of mean arterial pressure) expressed as a percentage was used as an index of blood pressure variability. Coefficients averaged 7.0% in intact lambs and 12.1% in barodenervated lambs (P less than 0.001), signifying considerably increased variability of mean arterial pressure after barodenervation. Mean arterial pressure averaged over 24 hours was not different between the two groups prior to 120 days (0.8) of gestation. Between 120 days and term, mean pressure was significantly greater in the denervated fetuses (65 cm H2O) than in the sham-operated controls (60 cm H2O, P less than 0.025). These data demonstrate that a baroreceptor-blood pressure reflex functions during late gestational development in lambs and signify an important role of arterial baroreceptors in regulating fetal arterial pressure. Failure to regulate arterial pressure in the barodenervated fetus could result in significant alterations in placental perfusion and exchange, and in the regional delivery of oxygen and substrates to developing organs in these animals.

Animals↗

Gas Exchange Characteristics of the Submerged Aquatic Crassulacean Acid Metabolism Plant, Isoetes howellii.

The submerged aquatic plant Isoetes howellii Engelmann possesses Crassulacean acid metabolism (CAM) comparable to that known from terrestrial CAM plants. Infrared gas analysis of submerged leaves showed Isoetes was capable of net CO(2) uptake in both light and dark. CO(2) uptake rates were a function of CO(2) levels in the medium. At 2,500 microliters CO(2) per liter (gas phase, equivalent to 1.79 milligrams per liter aqueous phase), Isoetes leaves showed continuous uptake in both the light and dark. At this CO(2) level, photosynthetic rates were light saturated at about 10% full sunlight and were about 3-fold greater than dark CO(2) uptake rates. In the dark, CO(2) uptake rates were also a function of length of time in the night period. Measurements of dark CO(2) uptake showed that, at both 2,500 and 500 microliters CO(2) per liter, rates declined during the night period. At the higher CO(2) level, dark CO(2) uptake rates at 0600 h were 75% less than at 1800 h. At 500 microliters CO(2) per liter, net CO(2) uptake in the dark at 1800 h was replaced by net CO(2) evolution in the dark at 0600 h. At both CO(2) levels, the overnight decline in net CO(2) uptake was marked by periodic bursts of accelerated CO(2) uptake. CO(2) uptake in the light was similar at 1% and 21% O(2), and this held for leaves intact as well as leaves split longitudinally. Estimating the contribution of light versus dark CO(2) uptake to the total carbon gain is complicated by the diurnal flux in CO(2) availability under field conditions.

Journal Article↗

Role of the carotid chemoreceptors in regulation of inspiratory onset.

We studied the effect of intermittent tidal breaths of CO2-enriched air (3-9% CO2) on the duration of expiratory time (TE) in five trained dogs, before and after (3 dogs) bilateral surgical denervation of the carotid bodies (CBD). During studies the dogs lay quietly, either awake or in nonrapid-eye-movement sleep, and breathed through a cuffed endotracheal tube inserted via a chronic tracheostomy. Studies were conducted during bilateral blockade of the cervical vagus nerves (VB), achieved by circulating cold alcohol through radiators placed around exteriorized vagal skin loops. Prior to CBD, single breaths of CO2 significantly shortened TE and thus advanced the onset of the subsequent inspiration. Further, the decrease in TE induced by the CO2 stimulus was in direct proportion to the inspired CO2 concentration. Thus 3% CO2 shortened TE by 1.82 +/- 0.93 (SD) s, and 9% CO2 by 3.44 +/- 1.53 s. Changes in TE occurred in the absence of associated changes in either tidal volume or inspiratory time. After CBD, test breaths of CO2 failed to shorten TE during VB. We conclude that the carotid bodies have the ability to mediate changes in the timing of inspiratory onset in response to a transient CO2 stimulus.

Animals↗

Function of the future respiratory system in the growth retarded fetal sheep.

The development of the future air breathing respiratory system was investigated in eight carunclectomised fetal sheep and five control fetal animals over the last third of gestation (approximately day 100-day 145). Carunclectomy resulted in the test fetal animals being hypoxaemic, hypercapnic, hypoglycaemic and acidotic. All fetal animals were chronically instrumented with diaphragmatic electromyographic leads, fetal jugular vein and carotid artery catheters, an amniotic fluid catheter and small electrocardiographic leads placed on the chest wall. There was evidence of a significant, but small, reduced relative lung size in the carunclectomised animals by day 140 without corresponding relative changes in the weight of the brain, liver, or heart. Diaphragmatic electromyograph (EMG) was analysed in detail over the last third of gestation. In both groups of animals, the normal reduction in fetal 'breathing' rate, and the normal increase in fetal apnoea was noted with increasing periods of diaphragmatic silence as fetal apnoea was noted with increasing periods of diaphragmatic silence as gestation advanced. Linear regression analyses revealed that fetal breathing rate was significantly reduced over the last third of gestation, whilst fetal apnoea significantly increased in the carunclectomised animals. Average total integrated diaphragmatic activity was reduced prior to 120 days. This reduction was evident in the strength of each diaphragmatic contraction before 110 days. In three test and three control animals, histochemical analyses were undertaken to fibre type the muscles of the diaphragm. Fatigue resistant fibres were significantly reduced in the carunclectomised fetuses, and fibre diameters were diminished. Centroid analyses of the power spectrum of the diaphragmatic EMG did not however support the concept of increased muscle fatigue in the test animals.

Animals↗

Induction of reduced photorespiratory activity in submersed and amphibious aquatic macrophytes.

Incubation under water in a 30 C/14-hour or 12 C/10-hour photoperiod caused the CO(2) compensation points of 10 aquatic macrophytes to decrease below 25 or increase above 50 microliters CO(2) per liter, respectively. Submerged and aerial leaves of two amphibious angiosperms (Myriophyllum brasiliense and Proserpinaca palustris) maintained high compensation points when incubated in air but, when the submerged or aerial leaves of Proserpinaca were incubated under water, the compensation points dropped as low as 10. This suggests that, in addition to temperature and photoperiod, some factor associated with submergence regulates the compensation point of aquatic plants. In the high-compensation point plants, photorespiration, as a percentage of net photosynthesis, was equivalent to that in terrestrial C(3) plants. For Hydrilla verticillata, the decreasing CO(2) compensation points (110, 40, and 10) were associated with reduced photorespiration, as indicated by decreased O(2) inhibition, decreased rates of CO(2) evolution into CO(2)-free air, and increased net photosynthetic rates.The decrease in the CO(2) compensation points of Hydrilla, Egeria densa, and Cabomba caroliniana was accompanied by an increase in the activity of phosphoenolpyruvate, but not of ribulose bisphosphate, carboxylase. In Hydrilla, several C(4) enzymes also increased in activity to the following levels (micromoles per gram fresh weight per hour): pyruvate Pi dikinase (35), pyrophosphatase (716), adenylate kinase (525), NAD and NADP malate dehydrogenase (6565 and 30), NAD and NADP malic enzymes (239 and 44), and aspartate and alanine aminotransferases (357 and 85), whereas glycolate oxidase (6) and phosphoglycolate and phosphoglycerate phosphatases (76 and 32) showed no change. Glycolate dehydrogenase and phosphoenolpyruvate carboxykinase were undetectable. The reduced photorespiration in these plants may be due to increased CO(2) fixation via a C(4) acid pathway. However, for three Myriophyllum species, some other mechanism appears operative, as phosphoenolpyruvate carboxylase was not increased in the low compensation point state, and ribulose bisphosphate carboxylase remained the predominant carboxylation enzyme.

Journal Article↗

Development of patterns of respiratory activity in unanesthetized fetal sheep in utero.

Respiratory activity (diaphragmatic electromyogram) was recorded in six unanesthetized in utero fetal lambs, between 0.7 of gestation and term. Respiratory patterns generated by the fetus showed developmental changes that included 1) an emergence of a periodic modulation of respiratory rate producing alternating active and quite phases (mean cycle length of 37 min between 130 and 140 days' gestation; 2) an increase in percentage apnea (expiratory time greater than 10 s) from 20% at 110 days to 60% at 140 days; and 3) a linear decrease in the 2-h average respiratory rate, while mean rate during active phases showed no consistent gestational decline. Electrocortical and electroocular activity was monitored in three of six fetuses; however, discrete sleep state patterns could not be consistently identified. The results demonstrate a gestational change in the respiratory patterns of the developing fetus and suggest an orderly maturation of the mechanisms controlling respiratory neuronal output.

Anesthesia↗

Hypercapnic stimulation of respiratory activity in unanesthetized fetal sheep in utero.

Respiratory responses to hypercapnia were studied in seven chronic in utero fetal lambs between 105 and 138 days' gestation (16 expts). Fetal arterial CO2 tension was raised (mean increase 9.9 Torr) by altering maternal inspired gas concentrations. Diaphragmatic electromyogram (EMG) was recorded as the index of respiratory activity. Electrocortical and electroocular activity (3 fetuses) were monitored in an attempt to define sleep state. Average respiratory rate increased (90%) and fetal apnea decreased (60%) during hypercapnia. Mean respiratory rate during "on" periods (greater than 6 EMG bursts/min) increased significantly during hypercapnia throughout the gestational epoch studied. Mean duration of the inspiratory time (TI) showed no significant change. Variability in both rate and TI decreased in response to CO2 at all gestations. Integrated EMG activity per burst divided by TI increased significantly at all gestations; however, no gestational increase in responsiveness to CO2 was seen. Sleep states were not able to be consistently identified, and a quantifiable electrocortical response to CO2 was not observed. These results indicate a relatively early functional maturation of fetal respiratory responses to CO2.

Animals↗

Effect of carotid body denervation on arousal response to hypoxia in sleeping dogs.

We studied the arousal and ventilatory responses to hypoxia during sleep in three trained dogs, before and 1-4 wk after carotid body denervation (CBD). During the studies the dogs breathed through a cuffed endotracheal tube inserted via a chronic tracheostomy. Eucapnic progressive hypoxia was induced by a rebreathing technique, and arterial O2 saturation (Sao2) was measured with an ear oximeter. Sleep stage was determined by electroencephalographic and behavioral criteria. Following CBD, all dogs exhibited hypoventilation under resting conditions; hypoxic ventilatory responses during wakefulness, slow-wave sleep (SWS), and rapid-eye-movement (REM) sleep were less than 10% of control. Prior to CBD, hypoxic arousal occurred at Sao2 of 83.2 +/- 4.6% (mean +/- Se) during SWS and 70.6 +/-2.2% in REM sleep. Following CBD, arousal failed to occur during progressive desaturation to 60% in SWS and 50% in REM sleep, at which levels hypoxia was arbitrarily terminated. In a few studies following CBD where rebreathing was allowed to continue, the dogs occasionally failed to arouse at all and require active resuscitation. The results indicate a critical role for the carotid chemoreceptors in mediating the arousal response to hypoxia.

Animals↗

Carotid chemoreceptors in ventilatory responses to changes in venous CO2 load.

We examined the role of the carotid chemoreceptors in the ventilatory response to changes in venous CO2 load in 12 awake sheep using a venovenous extracorporeal perfusion circuit and two carbon dioxide membrane lungs (CDML). Three of the sheep had undergone surgical denervation of the carotid bodies (CBD). In the nine intact sheep, as CO2 was removed from or added to the peripheral venous blood through the CDML under normoxic conditions, there was a linear relationship between the rate of pulmonary CO2 excretion (VCO2) and the resulting rate of ventilation over a VCO2 range of 0--800% of control, so that arterial PCO2 remained close to isocapnic. In contrast, in the three CBD sheep, the ventilatory response to changes in VCO2 was significantly decreased under normoxic conditions, resulting in marked hypercapnia. The results indicate that the carotid chemoreceptors exert a major influence on the ventilatory response to changes in venous CO2 load.

Animals↗

Role of the carotid body and of afferent vagal stimuli in the arousal response to airway occlusion in sleeping dogs.

We studied the independent effects of bilateral carotid body denervation and bilateral cold blockade of the vagus nerves on the arousal response to airway occlusion during sleep. Dogs breathed through a cuffed endotracheal tube inserted via a chronic tracheostomy, and airway occlusion was imposed at end-expiration and maintained until the moment of arousal. Arterial O2 saturation (SaO2) was measured with an ear oximeter, and sleep stage was determined by electroencephalographic and behavioral criteria. Mean +/- SE SaO2 values at arousal were 88.7 +/- 2.7% during slow-wave sleep, and 84.9 +/- 3.5% during rapid-eye-movement sleep (0.05 less than p less than 0.1). After carotid body denervation (2 dogs), arousal SaO2 values were less than 60% during slow-wave sleep and less than 50% during rapid-eye-movement sleep, at which time airway occlusion was arbitrarily terminated. In a few studies after denervation, when airway occlusion was maintained beyond these values, the dogs occasionally failed to arouse at all, and resuscitation was required. Bilateral cold blockade of the vagus nerves (2 dogs) resulted in no significant change in SaO2 at arousal. We concluded that the arousal response to airway occlusion is mediated primarily by the carotid bodies.

Afferent Pathways↗