Inspiratory Minute Ventilation Research Articles

Three levels of enhanced inspired CO2 or fasted-state on stress response activation in behaviorally inhibited humans and rats

Behavioral inhibition (BI) is believed to be a genetically determined trait that affects roughly 33% of the human population. These individuals tend to respond to stressful situations differently than their non-behaviorally inhibited (NBI) counterparts. In the rodent population, a similar behavioral/stress model exists. The Sprague-Dawley (SD) strain often acts as a “control” among rat strains and can be considered to be the rat equivalent to NBI individuals, and the Wistar-Kyoto (WKY) strain is the rodent equivalent to BI individuals. The differences in the activation of the sympathetic nervous system between chronically stressed and non-stressed populations remain unknown. Our current study tested the hypothesis BI individuals and WKY rats will have increased stress responses. In humans, we tested physiological responses to increasing levels of carbon dioxide (CO2) through analyses of breathing, heart rate, and blood pressure. The Adult Measure of Behavioral Inhibition (AMBI) survey was used to determine the presence of BI. A 15-minute control period baseline was completed followed by an acquisition period of five minutes of each 3%, 5%, and 7% CO2, respectively. Preliminary results were analyzed through a CO2 sensitivity slope (inspired minute ventilation ((L/min) / end-tidal CO2) and show that BI individuals had increased, exaggerated responses to the respiratory stressors across the three levels of enhanced CO2. In the rodent model, signaled lever-press avoidance was used to examine the activation of stress responses. Rats were trained to avoid mild foot shock using a tone warning signal. As demonstrated previously, WKY rats acquired a higher level of avoidance responses. Rats were then food-deprived overnight and subsequently retested on signal lever-press avoidance. Food deprivation did not affect the high rate of avoidance seen in WKY rats; however, food deprivation increased the SD rate of avoidance to nearly the level of WKY rats. Our data suggest that WKY rats do not respond to food deprivation when paired with lever-press avoidance; however, SD rats do. Simply, the addition of a stressor causes SD rats to behave more similarly to their WKY counterparts. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Randomized Clinical Trial Comparing the Effects of Antitussive Agents on Respiratory Center Output in Patients With Chronic Cough

Cough is produced by the same neuronal pool implicated in respiratory rhythm generation, and antitussive drugs acting at the central level, such as opioids, may depress ventilation. Levodropropizine is classified as a nonopioid peripherally acting antitussive drug that acts at the level of airway sensory nerves. However, the lack of a central action by levodropropizine remains to be fully established. We set out to compare the effects of levodropropizine and the opioid antitussive agent dihydrocodeine on the respiratory responses to a conventional CO2 rebreathing test in patients with chronic cough of any origin. Twenty-four outpatients (aged 39-70 years) with chronic cough were studied. On separate runs, each patient was randomly administered 60mg levodropropizine, 15mg dihydrocodeine, or a matching placebo. Subsequently, patients breathed a mixture of 93%oxygen and 7%CO2 for 5 min. Fractional end-tidal CO2 (Fetco2) and inspiratory minute ventilation (V˙i) were continuously monitored. Changes in breathing pattern variables were also assessed. At variance with dihydrocodeine, levodropropizine and placebo did not affect respiratory responses to hypercapnia (P< .01). The ventilatory increases by hypercapnia were mainly accounted for by a rise in the volume components of the breathing pattern. The results are consistent with a peripheral action by levodropropizine; the assessment of ventilatory responses to CO2 may represent a useful tool to investigate the central respiratory effects of antitussive agents. European Union Clinical Trials Register (EudraCT No.: 2013-004735-68); URL: https://www.clinicaltrialsregister.eu/.

From rest to stressed: endothelin-1 levels in young healthy smokers and non-smokers

IntroductionEndothelin-1 (ET-1) is a potent vasoconstrictor produced by vascular endothelial cells, and a known marker of endothelial dysfunction. However, the acute and chronic effects of smoking and nicotine gum on the ET-1 response to acute physical stress in young healthy smokers have not been investigated. MethodsHealthy smokers (n=35) and non-smokers (n=35) underwent an exercise test to exhaustion (maximal oxygen consumption) on a treadmill. Smokers were assessed a) after 12h smoking abstinence (termed chronic smoking), b) immediately after smoking one cigarette (termed acute smoking), and c) immediately after chewing nicotine gum. Blood was drawn immediately pre-exercise, and 3minutes post-exercise. During exercise, cardiorespiratory parameters were obtained breath-by-breath using an automated metabolic cart. Plasma ET-1 levels were quantified using enzyme-linked immunosorbent-assay. The above protocol was designed to incorporate exercise as a vascular stressor to reveal changes that would not be detected at rest. ResultsMean age was 28.6±7.2years and body mass index (BMI) was 23.6±3.2kg/m2. Post-exercise ET-1 levels were significantly lower than pre-exercise levels in non-smokers (P<0.001) and smokers under all three conditions (P=0.005, P<0.001, P=0.001, respectively). There were no differences in post-exercise ET-1 levels between non-smokers and smokers under all three conditions, however the absolute and relative decrease in ET-1 levels was significantly smaller in chronic smokers compared with non-smokers (P=0.007 and P=0.004). Chronic smokers had a significantly lower exercise-induced change in tidal volume (P=0.050), fraction of expired CO2 (P=0.021), oxygen consumption (P=0.005), carbon dioxide elimination (P=0.004) and peak expiratory flow (P=0.003) compared with non-smokers. Furthermore, the decrease in ET-1 observed in non-smokers in response to exercise was significantly associated with exercise induced-changes in inspiratory time, time for a tidal volume cycle, respiratory frequency, inspired minute ventilation and peak inspiratory flow. ConclusionsAn acute decrease of circulating ET-1 in response to acute maximal exercise in young healthy individuals was noted. Chronic smokers had a significantly diminished decrease in ET-1 compared with non-smokers, however there were no significant differences in the ET-1 response between smokers under the three smoking conditions. Smokers were not able to achieve the same exercise-induced changes in cardiorespiratory parameters as non-smokers. By incorporating exercise as a vascular stressor in our study, we have taken a novel approach to provide evidence of an altered ET-1 and cardiorespiratory response that would not otherwise be observed at rest in young active healthy smokers.

Leptin and the control of pharyngeal patency during sleep in severe obesity

Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep. An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m(2), age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m(2), age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions. Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax (r(2) = 0.44, P < 0.001), ΔVI (r(2) = 0.40, P < 0.001), and ΔPCRIT (r(2) = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth. Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility.

Update in Sleep Medicine 2011

Although it is unclear why all respiratory events in obstructive sleep apnea (OSA) are not terminated with a recognizable cortical arousal, it has been hypothesized that events terminated without arousal may lead to more stable breathing. Jordan and colleagues attempted to define the physiologic parameters immediately related to stable breathing, including airflow, genioglossus and tensor palatini muscle activity, and airway resistance, after respiratory events terminated with or without cortical arousal (1). They hypothesized that respiratory events terminated without cortical arousal would produce less hyperventilation and less secondary events due to higher pharyngeal dilator activity compared with events with arousal. Sixteen patients with mild to severeOSA already treated with continuous positive airway pressure (CPAP) were studied. Using a sudden drop in CPAP pressure to subtherapeutic levels, they found that respiratory events terminated without arousal led to less hyperventilation and less secondary events (primarily hypopneas) compared with events terminated with arousal. This reduction in inspiredminute ventilation and subsequent events was not accounted for by differences in residual pharyngeal dilator activity. Specifically, secondary events were marked by less flow limitation and greater pharyngeal dilator activity relative to the initial event whether cortical arousal was present or not. These findings question the notion of arousal predisposing patients to further obstructive events.

Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration

We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2-3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT(1) receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t)SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla-spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e.g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EH rats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration.

μ-Opioid receptor agonist injections into the presumed pre-Bötzinger complex and the surrounding region of awake goats do not alter eupneic breathing

Opioids are clinically important in the alleviation of pain. An undesirable side effect of opioids is depression of breathing. Data from isolated preparations suggest this effect is due to attenuation of discharge activity of neurons in the pre-Bötzinger complex (preBötzC), a medullary area with respiratory rhythmogenic properties. The purpose of this study was to examine how [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), a mu-opioid receptor agonist, affected breathing after injection into the presumed preBötzC of the adult awake goat. We hypothesized that DAMGO would cause breathing to decrease and become irregular when injected into the presumed preBötzC and the surrounding region of the conscious animal. We further hypothesized that ventilatory sensitivity to CO(2) and hypoxia would be blunted after the injection of DAMGO. Microtubules were bilaterally implanted into the presumed preBötzC of 10 adult female goats. After recovery from the surgery, DAMGO (0.5-10 mul, 1 nM-10 muM) was injected into the presumed preBötzC during the awake state. DAMGO had no effect on pulmonary ventilation [inspiratory minute ventilation (Vi)], respiratory rhythm and pattern, the activation pattern of inspiratory and expiratory muscles, or arterial blood gases during eupneic breathing conditions (P > 0.10). However, DAMGO attenuated (P < 0.05) the evoked increase in breathing frequency when inspired CO(2) was increased, and DAMGO attenuated the Vi response to reduction of inspired O(2) to 10.8% (P < 0.05). We conclude that our data do not provide support for the concept that in awake mammals opioid depression of breathing is due to a directed action of opioids on preBötzC neurons.

Adaptation of ventilation to ‘buffeting’ in vehicles

Short exposures to buffeting in a vehicle driving over rough terrain induce an increase in the frequency of respiration resulting in hyperpnoea and hypocapnia. The present study investigates the adaptation to buffeting-induced hyperpnoea. We monitored ventilation and cardiovascular function in nine healthy young adults prior to, throughout and post a 30 minute simulation of buffeting. All subjects had a consistent elevation of respiratory frequency throughout motion. End-tidal CO(2) decreased during the first 5 minutes of buffeting due to a transient increase in minute ventilation. Elevation of respiratory frequency was facilitated by shortening of inspiration without change in expiratory time. Tidal volume was maintained which resulted in an increase in mean inspiratory flow during buffeting. At later stages of motion there was a partial return to normal for mean inspiratory flow, minute ventilation and end-tidal CO(2)because of a slight reduction in tidal volume whilst inspiratory time remained shortened. Salivary cortisol levels were unaffected by motion, suggesting that the hyperpnoea was not secondary to non-specific stress. The cause of elevated respiratory frequency during buffeting could be due to mechanical action on the torso, vestibular-respiratory drive or a protective reinforcement of the torso.

Respiratory effects of chronic in utero methadone or morphine exposure in the neonatal guinea pig

This study uses a neonatal guinea pig model to compare the effects of in utero methadone or morphine exposure upon breathing control. We hypothesize that in utero methadone exposure will result in similar respiratory disturbances to those seen in morphine exposed neonates, but that the onset will be slower and the duration longer, due to methadone's longer elimination half-life. Pregnant Dunkin–Hartley guinea pigs received once-daily injections of methadone, morphine, or vehicle (saline) during the last half of gestation and pups were studied 3, 7, or 14 days after birth. In utero methadone or morphine exposure resulted in decreased birth weight compared to vehicle, and pups experienced a withdrawal syndrome which included increased locomotor activity and respiratory disturbances but no change in rectal temperature. Both opioid exposures increased inspiratory minute ventilation during CO 2 challenge at 3 days after birth, but only in morphine exposed pups was this withdrawal effect still present on day 7. Surprisingly, only morphine exposure increased inspiratory minute ventilation during room air breathing. We conclude that in utero methadone exposure is not equivalent to in utero morphine exposure. With respect to neonatal respiratory control, methadone-induced changes in respiration are only apparent during hypercapnia.

Inspiratory Flow Rates During Hard Work When Breathing Through Different Respirator Inhalation and Exhalation Resistances

There has been a long-standing debate regarding the adequacy of airflow rates used in respirator certification testing and whether these test flow rates underestimate actual values. This study investigated breath by breath inspiratory peak flow rate, minute ventilation, and instantaneous flow rates of eight young, healthy volunteers walking on a treadmill at 80–85% of maximal aerobic capacity until exhaustion while wearing an air-purifying respirator with one of eight combinations of inhalation and exhalation resistance. An analysis of variance was performed to identify differences among the eight conditions. Scheffe's post hoc analysis indicated which means differed. The group of conditions with the highest average value for each parameter was identified and considered to represent a worst-case scenario. Data was reported for these conditions. A Gaussian distribution was fit to the data and the 99.9% probability levels determined. The 99.9% probability level for the peak and instantaneous flow rates were 374 L/min and 336 L/min, respectively. The minute ventilation distribution was not Gaussian. Less than 1% of the recorded minute ventilations exceeded 135 L/min. Instantaneous flow rates exceeded the National Institute for Occupational Safety and Health's respirator test standards of 64, 85, and 100 L/min constant flow 91%, 87%, and 82% of the time, respectively. The recorded minute ventilations exceeded the 40 L/min minute ventilation test standard (for tests with a sinusoidal flow pattern) 100% of the time. This study showed that young, healthy respirator wearers generated peak flow rates, minute ventilations, and instantaneous flow rates that consistently exceeded current test standards. Their flow rates should be higher than those of a respirator wearer performing occupational work and could be considered upper limits. Testing respirators and respirator cartridges using a sinusoidal breathing pattern with a minute ventilation of 135 L/min (peak flow rate approximately 424 L/min) would encompass 99% of the recorded minute ventilations and 99.9% of the predicted peak and instantaneous flow rates from this study and would more accurately reflect human respiration during strenuous exercise.

Comparison of ventilation during exercise in horses wearing half- and full-face masks

AbstractSeveral studies have shown that the placement of a face mask on a horse can have effects on ventilation, gas exchange and the cardiovascular system during exercise. The aim of the present study was to determine if airflow and ventilation measured with the same ultrasonic flowmeters were different during exercise between horses wearing half- (HM) and full-face (FM) masks. Five clinically healthy Thoroughbred horses with no history of respiratory disease were studied in an unbalanced crossover design. They were exercised on a treadmill at speeds between 1.7 and 11ms−1on a 3° incline wearing both masks. The following variables were recorded: peak inspired (PIF) and peak expired flow rates (PEF), inspiratory tidal volume (VT), respiratory rate (fR), inspiratory minute ventilation (VE), inspiratory time, (TI), expiratory time (TE), total breath time (TT), end tidal oxygen (ETO2), end tidal carbon dioxide (ETCO2) and heart rate (HR). A mask by speed of exercise interaction term was not significant for any of the models. The PEF (mean difference 12.91s−1; lower and upper 95% CI 7.6 and 18.21s−1, respectively;P&lt;0.0001) and ETO2(mean difference 0.77%; lower and upper 95% CI 0.48 and 1.00%, respectively;P&lt;0.0001) were significantly greater and ETCO2was significantly lower (mean difference −1.3%; lower and upper 95% CI −2.0 and 0.7%, respectively;P&lt;0.0001) with the FM compared with the HM. There was also a trend for inspiredVEto be higher with the FM compared with the HM (mean difference 1021min−1; lower and upper 95% CI 26 and 1781 min−1, respectively; non-significant). We conclude that the HM may impair ventilation in the horse during exercise compared with the FM, despite the latter having a greater deadspace.

Variability of the Initial Phase of the Ventilatory Response to Hypoxia in Sleeping Infants

Most of the available data on the hypoxic ventilatory response (HVR) in infants has been obtained in quiet sleep (QS), and only one study has made repeated tests in the same infant. We aimed to gain a more complete knowledge of the maturation and consistency of the initial phase of the HVR by performing multiple tests in both QS and active sleep (AS) over the first 6 mo of life in term infants. Fifteen healthy term infants were studied with daytime polysomnography longitudinally at 2-5 wk, 2-3 mo, and 5-6 mo after birth. Each infant received multiple hypoxic (15% O2, balance N2) challenges (three or more) in both AS and QS. In AS, infants consistently aroused to hypoxia; however, in QS, infants both aroused and failed to arouse. The initial phase of the HVR varied considerably between infants with the changes in ventilation/kg [SD of inspired minute ventilation per kilogram of body weight (V(I)/kg)] being more variable during AS than QS at all three ages and overall decreasing with postnatal age in both sleep states. The variability between replicate V(I)/kg measurements was also significantly greater in AS compared with QS at 2-5 wk postnatal age. There was no evidence of habituation to repeated hypoxic tests in either sleep state. Our study has demonstrated that the initial phase of the HVR is variable both between and within term infants in both AS and QS, with responses being markedly more variable during AS, and becoming more consistent with increasing postnatal age. By performing only one test or by failing to account for arousal responses, previous studies may not have detected the natural variation of the infant HVR.

Buprenorphine induces ceiling in respiratory depression but not in analgesia

We measured the effect of two weight adjusted i.v. doses (0.2 mg per 70 kg and 0.4 mg per 70 kg) of the potent opioid buprenorphine on analgesia and respiratory depression in healthy volunteers. The aim of the study was to compare buprenorphine's behaviour with respect to the occurrence of ceiling (or apparent maximum) in these typical micro-opioid protein-(MOP) receptor effects. Ten subjects (5 males) received 0.2 mg per 70 kg, 10 others (5 males) 0.4 mg per 70 kg i.v. buprenorphine. Steady-state inspired minute ventilation at a fixed end-tidal Pco(2) of 7 kPa was measured before drug infusion and at regular intervals after drug infusion. Experimental pain was induced using transcutaneous electrical stimulation and a gradually increasing current. Pain tolerance was measured at regular intervals before and after drug infusion. The studies lasted 8 h. After infusion of the drug ventilation showed a rapid decline and reached peak depression between 150 and 180 min after drug administration. This effect was dose-independent with respect to timing and magnitude. At peak respiratory depression minute ventilation was 13.1 (sd 1.8) litre min(-1) in the 0.2 mg group vs 12.0 (sd 1.3) litre min(-1) in the 0.4 mg group (n.s.). At buprenorphine 0.2 mg a small short-lived analgesic effect was observed with a maximum increase in pain tolerance current of 6.7 (sd 2.8) mA occurring at 75 min after drug administration. Peak analgesic effect was 29% above baseline current. In contrast, buprenorphine 0.4 mg caused a large and long-lived analgesic effect with a maximum increase in pain tolerance current of 23.8 (sd 7.4) mA occurring at 130 min after drug administration. Peak analgesic effect was 160% above baseline current (0.4 vs 0.2 mg, P<0.01). While buprenorphine's analgesic effect increased significantly, respiratory depression was similar in magnitude and timing for the two doses tested. We conclude that over the dose range tested buprenorphine displays ceiling in respiratory effect but none in analgesic effect.

Effect of a Repeated Series of Intermittent Hypoxic Exposures on Ventilatory Response in Humans

The purpose of this study was to elucidate the magnitude and the time course of ventilatory changes resulting from a repeated series of hypoxic exposures. Eight healthy males participated in the present study. The subjects spent 1 h/day in normobaric hypoxia (12% inspired oxygen). Inspired minute ventilation (V(I)), end-tidal partial pressure of carbon dioxide (P(ET(CO2))), and arterial oxygen saturation (SaO2) were measured in a hypoxic tent. These measurements were taken for 10 consecutive days (series 1), and were taken again after the subjects had been away from hypoxic exposure for 1 month (series 2). P(ET(CO2)) decreased and SaO2 increased progressively in the hypoxic tent during the 10 days of intermittent hypoxia in series 1. At the onset of series 2 (days 1 to 3), P(ET(CO2)) was significantly lower and SaO2 was significantly higher than those on day 1 during series 1. These results suggest that humans who have had previous hypoxic exposure adapt sooner to hypoxic condition due to an increase in the magnitude of hyperventilation in the first few days of a series of reexposures to hypoxia.

Vestibulo-Cardiorespiratory Responses at the Onset of Chair Rotation in Endurance Runners

Stimulation of the vestibular system has been reported to elicit ventilatory and circulatory changes in humans. The purpose of this study was to clarify the characteristics of vestibular-mediated ventilatory and circulatory responses in male endurance runners at the onset of passive chair rotation, which selectively stimulates the semicircular canals. Fourteen runners and 14 male untrained subjects participated. The vestibular stimulus test, which consists of 180 degrees chair rotations (left or right half-turns on an earth-vertical axis) for a duration of 2 s, was carried out on each subject. Inspiratory minute ventilation, tidal volume, respiratory frequency, heart rate, and blood pressure were measured by breath-by-breath and beat-to-beat techniques before, during, and after the chair rotation for a total of 60 s. It was found in this study that (i) the relative change of minute ventilation response in the endurance runners was significantly (P < 0.05) greater than in the untrained subjects during and after the rotation, and that (ii) no significant group differences were observed in heart rate and mean blood pressure responses during and after the rotation. In conclusion, vestibular-mediated ventilatory response, but not circulatory response, at the onset of the chair rotation in the endurance runners was significantly greater than that in the untrained subjects. The results from the present study suggest that an increase in vestibulo-ventilatory response would be attributed to an adaptation to long-term endurance training.

Associative conditioning with leg cycling and inspiratory resistance enhances the early exercise ventilatory response in humans.

Repeated trials of hypercapnic exercise [deltaPET CO2 = 7 (1) mmHg] augment the increase in inspired minute ventilation and tidal volume (V(T)) in the early phase of subsequent trials of unencumbered exercise alone. The increase in V(T) in the first 20 s of exercise was correlated to the increase in V(T) evoked during hypercapnic exercise trials, suggesting that the evoked increase in V(T) during conditioning may be a factor in mediating associative conditioning. To test this hypothesis, inspiratory resistive loading (IRL) was employed to evoke an increase in V(T) [deltaV(T) = 0.4 (0.1) I(BTPS)] during conditioning exercise trials [IRL + EX; deltaP(ET)CO2 = 2 (l) mmHg]. IRL + EX associative conditioning elicited a significant augmentation of the early minute ventilation (+46%) and V(T) (+100%) responses to subsequent unencumbered exercise. The latter was correlated to the evoked increase in V(T) during associative conditioning with IRL + EX. The results support the hypothesis that an evoked increase in V(T) during associative conditioning could be a factor in eliciting long-term modulation of minute ventilation in subsequent unencumbered exercise. The results further indicated that the modulation of ventilation early in exercise is not due to sensitisation to repeated trials of either IRL or exercise alone. Associative conditioning may shape the ventilatory response to exercise through a process of motor learning. Data are presented as mean (SEM) unless otherwise stated.

Changes of Respiratory Mechanics in Pregnant Woman under General Anesthesia for Cesarean Section

Background: In pregnant woman, the respiratory system is influenced by the hormonal environment and an enlarged gravid uterus. After delivery of the fetus, and contraction of the uterus, changes in the respiratory system produced by the mechanical effect of the gravid uterus may decrease or be reversed. We designed this study to observe changes in the respiratory mechanics in pregnant woman under general anesthesia for cesarean section. Methods: 15 pregnant women at term, ASA 1 were studied. Induction was performed with thiopental/succinylcholine and maintained with , and enflurane until delivery. Just before delivery, enflurane was discontinued. Vecuronium was given at 0.1 mg/kg iv 4 min after induction, and after delivery, 1 mg was given as needed. Inspired tidal volume, expired tidal volume, inspired minute ventilation, expired minute ventilation, airway peak pressure, plateau pressure, expired volume during the first 1 second/expired tidal volume (V1.0), dynamic compliance and end-tidal were continuously measured just after induction, at delivery and 5, 10, 15, 20, 25, 30, 40 and 50 min after delivery. Blood pressure, heart rate and oxygen saturation were also measured. Results: Compared to the value after induction, values after delivery showed no significant changes in inspired tidal volume or minute volume, but significantly increased in expired tidal volume and minute volume and dynamic compliance, and a significant decrease in airway peak pressure, plateau pressure, V1.0 and end-tidal . Blood pressure and heart rate increased significantly after induction, compared to before induction. Oxygen saturation was maintained at 99-100%. Conclusions: After delivery, the effects of the gravid uterus on the respiratory system rapidly disappeared, in particular changes of pressure in the airway preceded the respiratory volume changes.

Significant Pulmonary Response to a Brief High-Level, Nose-Only Nitrogen Dioxide Exposure: An Interspecies Dosimetry Perspective

Brief, high-level nitrogen dioxide (NO 2) exposures are major hazards during fires and heat-generating explosions. To characterize the lung response to a brief high-level NO 2 exposure, we exposed two groups ( n = 5) of 325–375 g, male, Sprague–Dawley rats to either 200 ± 5 ppm (376 ± 9 mg/m 3) NO 2 or room air for 15 min. The rats were nose-only exposed in a multiport exposure chamber fitted with pressure transducers to monitor their respiration during exposure. One hour after exposure, we euthanized the rats, collected blood samples, lavaged the lungs with warm saline, and then excised them. One lung lobe was cooled to −196°C and used for low-temperature electron paramagentic resonance (EPR) analysis. The remainder was homogenized and used for biochemical analyses. Inspired minute ventilation ( V i) during exposure decreased 59% ( p < 0.05). Calculated total inspired dose was 0.880 mg NO 2. In lung lavage, both total and alveolar macrophage cell counts declined (∼75%, p < 0.05), but epithelial cell count increased 8.5-fold. Lung weight increased 40% ( p < 0.05) after exposure. In the blood, potassium and methemoglobin increased 45 and 18% ( p < 0.05), respectively; glucose, lactate, and total hemoglobin were not altered significantly. EPR analysis of lung tissue revealed hemoglobin oxidation and carbon-centered radical formation. Vitamins E and C and uric acid were depleted, and lipid peroxidation measured by three different methods (TBARS, conjugated dienes, and fluorescent peroxidation end products) was elevated, but total protein, DNA, and lipid contents were unchanged. These observations combined demonstrate that a brief (15 min) high-level (200 ppm) NO 2 exposure of rats was sufficient to cause significant damage. However, comparison of the exposure dose normalized to rat body weight with previously reported sheep and estimated human values revealed significant differences. This raises a question about interspecies dosimetry and species-specific responses when animal data are extrapolated to humans and used for safety standard setting, particularly with high-level brief exposures.

Significant Pulmonary Response to a Brief High-Level, Nose-Only Nitrogen Dioxide Exposure: An Interspecies Dosimetry Perspective

Brief, high-level nitrogen dioxide (NO 2 ) exposures are major hazards during fires and heat-generating explosions. To characterize the lung response to a brief high-level NO 2 exposure, we exposed two groups ( n = 5) of 325–375 g, male, Sprague–Dawley rats to either 200 ± 5 ppm (376 ± 9 mg/m 3 ) NO 2 or room air for 15 min. The rats were nose-only exposed in a multiport exposure chamber fitted with pressure transducers to monitor their respiration during exposure. One hour after exposure, we euthanized the rats, collected blood samples, lavaged the lungs with warm saline, and then excised them. One lung lobe was cooled to −196°C and used for low-temperature electron paramagentic resonance (EPR) analysis. The remainder was homogenized and used for biochemical analyses. Inspired minute ventilation ( V i ) during exposure decreased 59% ( p < 0.05). Calculated total inspired dose was 0.880 mg NO 2 . In lung lavage, both total and alveolar macrophage cell counts declined (∼75%, p < 0.05), but epithelial cell count increased 8.5-fold. Lung weight increased 40% ( p < 0.05) after exposure. In the blood, potassium and methemoglobin increased 45 and 18% ( p < 0.05), respectively; glucose, lactate, and total hemoglobin were not altered significantly. EPR analysis of lung tissue revealed hemoglobin oxidation and carbon-centered radical formation. Vitamins E and C and uric acid were depleted, and lipid peroxidation measured by three different methods (TBARS, conjugated dienes, and fluorescent peroxidation end products) was elevated, but total protein, DNA, and lipid contents were unchanged. These observations combined demonstrate that a brief (15 min) high-level (200 ppm) NO 2 exposure of rats was sufficient to cause significant damage. However, comparison of the exposure dose normalized to rat body weight with previously reported sheep and estimated human values revealed significant differences. This raises a question about interspecies dosimetry and species-specific responses when animal data are extrapolated to humans and used for safety standard setting, particularly with high-level brief exposures.

Determinants of long-term facilitation in humans during NREM sleep.

Long-term facilitation (LTF) is a prolonged increase in ventilatory motor output after episodic peripheral chemoreceptor stimulation. We have previously shown that LTF is activated during sleep following repetitive hypoxia in snorers (Babcock MA and Badr MS. Sleep 21: 709-716, 1998). The purpose of this study was 1) to ascertain the relative contribution of inspiratory flow limitation to the development of LTF and 2) to determine the effect of eliminating inspiratory flow limitation by nasal CPAP on LTF. We studied 25 normal subjects during stable non-rapid eye movement sleep. We induced 10 episodes of brief repetitive isocapnic hypoxia (inspired O(2) fraction = 8%; 3 min) followed by 5 min of room air. Measurements were obtained during control and at 20 min of recovery (R(20)). During the episodic hypoxia study, inspiratory minute ventilation (Vi) increased from 6.7 +/- 1.9 l/min during the control period to 8.2 +/- 2.7 l/min at R(20) (122% of control; P < 0.05). Linear regression analysis confirmed that inspiratory flow limitation during control was the only independent determinant of the presence of LTF (P = 0.005). Six subjects were restudied by using nasal continuous positive airway pressure to ascertain the effect of eliminating inspiratory flow limitation on LTF. Vi during the recovery period was 97 +/- 10% (P > 0.05). In conclusion, 1) repetitive hypoxia in sleeping humans is followed by increased Vi in the recovery period, indicative of development of LTF; 2) inspiratory flow limitation is the only independent determinant of posthypoxic LTF in sleeping human; 3) elimination of inspiratory flow limitation abolished the ventilatory manifestations of LTF; and 4) we propose that increased Vi in the recovery period was a result of preferential recruitment of upper airway dilators by repetitive hypoxia.