Effects of CO2 breathing on ventilatory response to sustained hypoxia in normal adults

The relationship between CO2 and ventilatory response to sustained hypoxia was examined in nine normal young adults. At three different levels of end-tidal partial pressure of CO2 (PETCO2, approximately 35, 41.8, and 44.3 Torr), isocapnic hypoxia was induced for 25 min and after 7 min of breathing 21% O2, isocapnic hypoxia was reinduced for 5 min. Regardless of PETCO2 levels, the ventilatory response to sustained hypoxia was biphasic, characterized by an initial increase (acute hypoxic response, AHR), followed by a decline (hypoxic depression). The biphasic response pattern was due to alteration in tidal volume, which at all CO2 levels decreased significantly (P less than 0.05), without a significant change in breathing frequency. The magnitude of the hypoxic depression, independent of CO2, correlated significantly (r = 0.78, P less than 0.001) with the AHR, but not with the ventilatory response to CO2. The decline of minute ventilation was not significantly affected by PETCO2 [averaged 2.3 +/- 0.6, 3.8 +/- 1.3, and 4.5 +/- 2.2 (SE) 1/min for PETCO2 35, 41.8, and 44.3 Torr, respectively]. This decay was significant for PETCO2 35 and 41.8 Torr but not for 44.3 Torr. The second exposure to hypoxia failed to elicit the same AHR as the first exposure; at all CO2 levels the AHR was significantly greater (P less than 0.05) during the first hypoxic exposure than during the second. We conclude that hypoxia exhibits a long-lasting inhibitory effect on ventilation that is independent of CO2, at least in the range of PETCO2 studied, but is related to hypoxic ventilatory sensitivity.     

Ventilatory and gas exchange responses under spontaneous and fixed breathing modes during arm exercise

To evaluate the difference of ventilatory and gas exchange response differences between arm and leg exercise, six healthy young men underwent ramp exercise testing at a rate of 15 W.min-1 on a cycle ergometer separately under either spontaneous (SPNT) or fixed (FIX) breathing modes, respectively. Controlled breathing was defined as a breathing frequency (fb; 30 breaths.min-1) which was neither equal to, nor a multiple of, cranking frequency (50 rev.min-1) to prevent coupling of locomotion and respiratory movement, i.e., so-called locomotor-respiratory coupling (LRC). Breath-by-breath oxygen uptake (VO2), ventilation (VE), CO2 output (VCO2), tidal volume (VT), fb and end-tidal PCO2 (PETCO2) were determined using a computerized metabolic cart. Arm exercise engendered a higher level of VO2 at each work rate than leg exercise under both FIX and SPNT conditions. However, FIX did not notably affect the VO2 response during either arm or leg exercise at each work rate compared to SPNT. During SPNT a significantly higher fb and lower PETCO2 during arm exercise was found compared with leg exercise up to a fb of 30 breaths.min-1 while VE and VT were nearly the same. During fixed breathing when fb was fixed at a higher rate than during SPNT, a significantly lower PETCO2 was observed during both exercise modes. These results suggest that: 1) FIX breathing does not affect the VO2 response during either arm or leg exercise even when non-synchronization between limb locomotion movement and breathing rate was adopted; 2) at a fb of 30 breaths.min-1 FIX breathing induced a hyperventilation resulting in a lower PETCO2 which was not associated with the metabolic rate during either arm or leg exercise, showing that VE during only leg exercise under the FIX condition was significantly higher than under the SPNT condition.     

Effect of a single breath of 100% oxygen on respiration in neonates during sleep

To determine the effect of a single breath of 100% O2 on ventilation, 10 full-term [body wt 3,360 +/- 110 (SE) g, gestational age 39 +/- 0.4 wk, postnatal age 3 +/- 0.6 days] and 10 preterm neonates (body wt 2,020 +/- 60 g, gestational age 34 +/- 2 wk, postnatal age 9 +/- 2 days) were studied during active and quiet sleep states. The single-breath method was used to measure peripheral chemoreceptor response. To enhance response and standardize the control period for all infants, fractional inspired O2 concentration was adjusted to 16 +/- 0.6% for a control O2 saturation of 83 +/- 1%. After 1 min of control in each sleep state, each infant was given a single breath of O2 followed by 21% O2. Minute ventilation (VE), tidal volume (VT), breathing frequency (f), alveolar O2 and CO2 tension, O2 saturation (ear oximeter), and transcutaneous O2 tension were measured. VE always decreased with inhalation of O2 (P less than 0.01). In quiet sleep, the decrease in VE was less in full-term (14%) than in preterm (40%) infants (P less than 0.001). Decrease in VE was due primarily to a drop in VT in full-term infants as opposed to a fall in f and VT in preterm infants (P less than 0.05). Apnea, as part of the response, was more prevalent in preterm than in full-term infants. In active sleep the decrease in VE was similar both among full-term (19%) and preterm (21%) infants (P greater than 0.5). These results suggest greater peripheral chemoreceptor response in preterm than in full-term infants, reflected by a more pronounced decrease in VE with O2. The results are compatible with a more powerful peripheral chemoreceptor contribution to breathing in preterm than in full-term infants.     

Relaxation with biofeedback-assisted guided imagery: The importance of breathing rate as an index of hypoarousal

Fifteen men and 35 women, suffering from a number of psychological and somatic disorders, were taught to relax by biofeedback-assisted deep-diaphragmatic breathing together with guided mental imagery. No instructions were given about rate. Breathing rate and pattern, PETCO2, and EEG were monitored before training and after the first three 2-minute training trials (session 1). In 27 subjects (54%), breathing patterns and rate were noted to resemble those reported by meditation practitioners (3 to 5 b/min). The PETCO2 and EEG changes support a hypothesis of metabolic hypoarousal. Four subjects spontaneously reported experiencing altered awareness. A centrally mediated hypoarousal response is tentatively implicated.     

Relaxation with biofeedback-assisted guided imagery: the importance of breathing rate as an index of hypoarousal

Fifteen men and 35 women, suffering from a number of psychological and somatic disorders, were taught to relax by biofeedback-assisted deep-diaphragmatic breathing together with guided mental imagery. No instructions were given about rate. Breathing rate and pattern, PETCO2, and EEG were monitored before training and after the first three 2-minute training trials (session 1). In 27 subjects (54%), breathing patterns and rate were noted to resemble those reported by meditation practitioners (3 to 5 b/min). The PETCO2 and EEG changes support a hypothesis of metabolic hypoarousal. Four subjects spontaneously reported experiencing altered awareness. A centrally mediated hypoarousal response is tentatively implicated.     

Effect of acute hypercapnia on limb muscle contractility in humans

The effect of acute hypercapnia on skeletal muscle contractility and relaxation rate was investigated. The contractile force of fresh and fatigued quadriceps femoris (QF) and adductor pollicis (AP) was studied in normal humans by use of electrical stimulation. Maximum relaxation rate from stimulated contractions was measured for both muscles. Acute hypercapnia led to a rapid substantial reduction of contraction force. The respiratory acidosis after 9% CO2 was breathed for 20 min [mean venous blood pH 7.26 and end-tidal PCO2 (PETCO2) 65.1 Torr] reduced 20- and 100-Hz stimulated contractions of QF to 72.8 +/- 4.4 and 80.0 +/- 5.1% of control values, respectively. After 8 and 9% CO2 were breathed for 12 min, AP forces at 20- and 50-Hz stimulation were also reduced. Twitch tension of AP was reduced by a mean of 25.5% when subjects breathed 9% CO2 for 12 min [mean arterialized venous blood pH (pHav) 7.25 and PETCO2 66 Torr]. Over the range of 5% (pHav 7.38 and PETCO2 47 Torr) to 9% CO2, there was a linear relationship between twitch tension loss and pHav, arterialized venous blood PCO2, and PETCO2. Acute respiratory acidosis (mean PETCO2 61 Torr) increased the severity of low-frequency fatigue after intermittent voluntary contractions of AP. At 20 min of recovery, twitch tension was 63.2 +/- 13.4 and 46.8 +/- 16.4% of control value after exercise breathing air and 8% CO2, respectively. Acute hypercapnia (mean PETCO2 65.1 and 60.5 Torr) did not alter the maximum relaxation rate from tetanic contractions of fresh QF and from twitch tensions of AP.     

Incoherent oscillations of respiratory sinus arrhythmia during acute mental stress in humans

Respiratory sinus arrhythmia (RSA) has been widely used as a measure of the cardiac vagal control in response to stress. However, RSA seems not to be a generalized indicator because of its dependency on respiratory parameter and individual variations of RSA amplitude (A(RSA)). We hypothesized that phase-lag variations between RSA and respiration may serve as a normalized index of the degree of mental stress. Twenty healthy volunteers performed mental arithmetic task (ART) after 5 min of resting control followed by 5 min of recovery. Breathing pattern, beat-to-beat R-R intervals, and blood pressure (BP) were determined using inductance plethysmography, electrocardiography, and a Finapres device, respectively. The analytic signals of breathing and RSA were obtained by Hilbert transform and the degree of phase synchronization (λ) was quantified. With the use of spectral analysis, heart rate variability (HRV) was estimated for the low-frequency (LF) and high-frequency (HF) bands. A steady-state 3-min resting period (REST), the first 3 min (ART1), and the last 3 min (ART2) of the ART period (ranged from 6- to 19 min) and the last 3 min of the recovery period (RCV) were analyzed separately. Heart rate, systolic BP, and breathing frequency (f(R)) increased and λ, A(RSA), and HF power decreased from REST to ART (P < 0.01). The λ was correlated with normalized A(RSA) and the HF power. The decrease in λ could not be explained solely by the increase in f(R). We conclude that mental stress exerts an influence on RSA oscillations, inducing incoherent phase lag with respect to breathing, in addition to a decrease in RSA.     

The effect of 10% O2 on the continuous breathing induced by O2 or O2 plus cord occlusion in the fetal sheep.

Although the administration of 100% O2 alone or combined with umbilical cord occlusion induces continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990a), the individual contribution of O2 and cord occlusion to the response have not been determined. We hypothesized that if O2 is an important factor in the induction of continuous breathing, administration of O2 low enough (10%) to bring fetal arterial PO2 to about 20 torr while the fetus is breathing continuously should reverse these changes. Thus we subjected 12 chronically instrumented fetal sheep to 10% O2 for 10 minutes after the establishment of continuous breathing by O2 (4 fetuses; 137 +/- 1 days) or by O2 plus umbilical cord occlusion (8 fetuses; 134 +/- 1 days). Arterial PO2 decreased from about 250 torr to 20 torr during 10% O2. This induced a significant decrease in breathing output (EMGdi x f) related primarily to a decrease in frequency (f). In 3/5 experiments in 4 fetuses, with O2 alone, apnoea developed within 4 +/- 0.6 min; in 12/13 experiments in 8 fetuses, with added cord occlusion it developed at 5 +/- 0.6 min. With the decrease in PaO2, electrocortical activity (ECoG) switched from low to high-voltage within 6 minutes in 5/5 experiments (O2 alone) and in 11/13 (O2 plus cord occlusion). The findings suggest that umbilical cord occlusion alone is not sufficient to maintain breathing continuously and an increased PaO2 is needed. We speculate that in the fetus there is a vital link between PaO2, breathing and ECoG with low PaO2 inhibiting and high PaO2 favouring breathing and arousal.     

The effects of naloxone on the changes in breathing and behaviour induced by morphine in the foetal sheep

In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal.     

Role of carotid chemoreceptors and pulmonary vagal afferents during helium-oxygen breathing in ponies

Our purpose was to assess compensatory breathing responses to airway resistance unloading in ponies. We hypothesized that the carotid bodies and hilar nerve afferents, respectively, sense chemical and mechanical changes caused by unloading, hence carotid body-denervated (CBD) and hilar nerve-denervated ponies (HND) might demonstrate greater ventilatory responses when decreasing resistance. At rest and during treadmill exercise, resistance was transiently reduced approximately 40% in five normal, seven CBD, and five HND ponies by breathing gas of 79% He-21% O2 (He-O2). In all groups at rest, He-O2 breathing did not consistently change ventilation (VE), breathing frequency (f), tidal volume (VT), or arterial PCO2 (PaCO2) from room air-breathing levels. During treadmill exercise at 1.8 mph-5% grade in normal and HND ponies, He-O2 breathing did not change PaCO2 but at moderate (6 mph-5% grade), and heavy (8 mph-8% grade) work loads, absolute PaCO2 tended to decrease by 1 min of resistance unloading. delta PaCO2 calculated as room air minus He-O2 breathing levels at 1 min demonstrated significant changes in PaCO2 during exercise resistance unloading (P less than 0.05). No difference between normal and HND ponies was found in exercise delta PaCO2 responses (P greater than 0.10); however, in CBD ponies, the delta PaCO2 during unloading was greater at any given work load (P less than 0.05), suggesting finer regulation of PaCO2 in ponies with intact carotid bodies. During heavy exercise VE and f increased during He-O2 breathing in all three groups of ponies (P less than 0.05), although there were no significant differences between groups (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

顺式阿曲库铵在小儿全身麻醉中对气道功能的影响

目的:比较顺式阿曲库铵和阿曲库铵在小儿全麻中对气道功能的影响。方法:选取72名3-9岁患儿,男42例,女30例,采用随机表法将其分为观察组和对照组,每组36例。两组麻醉诱导都采用异丙酚,芬太尼,咪达唑仑。观察组使用顺式阿曲库铵0.15mg/kg,对照组组阿曲库铵0.5 mg/kg,比较两组小儿在插管后5 min、10 min、15 min、20 min患儿P_(ET)CO_2、P-PEAK、听诊呼吸音(粗、细湿啰音)、SPO_2变化四项指标来研究顺式阿曲库铵和阿曲库铵对呼吸系统的影响。结果:观察组注药后5 min、10 min、15 min、20 min时间点P_(ET)CO_2,P-PEAK变化趋势不明显,听诊呼吸音、SPO_2无明显变化(P0.05)。对照组在注药后的4个时间段P_(ET)CO_2、P-PEAK、听诊呼吸音、SPO_2有显著变化,随时间延长,P_(ET)CO_2,P-PEAK有明显增高,SPO_2逐渐下降情况(P0.05)。观察组和对照组相比,5 min、10 min、15 min、20 min各时间点观察组SPO_2高于对照组,PETCO_2、P-PEAK明显低于对照组,啰音发生的概率低于对照组,各时间点各项指标比较差异有统计学意义(P0.05)。结论:顺式阿曲库铵术中对小儿气道功能影响较小,肌松作用理想,可广泛应用于小儿临床麻醉。     

Changes in breathing when switching from nares to tracheostomy breathing in awake ponies

We assessed the consequences of respiratory unloading associated with tracheostomy breathing (TBr). Three normal and three carotid body-denervated (CBD) ponies were prepared with chronic tracheostomies that at rest reduced physiological dead space (VD) from 483 +/- 60 to 255 +/- 30 ml and lung resistance from 1.5 +/- 0.14 to 0.5 +/- 0.07 cmH2O . l-1 . s. At rest and during steady-state mild-to-heavy exercise arterial PCO2 (PaCO2) was approximately 1 Torr higher during nares breathing (NBr) than during TBr. Pulmonary ventilation and tidal volume (VT) were greater and alveolar ventilation was less during NBr than TBr. Breathing frequency (f) did not differ between NBr and TBr at rest, but f during exercise was greater during TBr than during NBr. These responses did not differ between normal and CBD ponies. We also assessed the consequences of increasing external VD (300 ml) and resistance (R, 0.3 cmH2O . l-1 . s) by breathing through a tube. At rest and during mild exercise tube breathing caused PaCO2 to transiently increase 2-3 Torr, but 3-5 min later PaCO2 usually was within 1 Torr of control. Tube breathing did not cause f to change. When external R was increased 1 cmH2O . l-1 . s by breathing through a conventional air collection system, f did not change at rest, but during exercise f was lower than during unencumbered breathing. These responses did not differ between normal, CBD, and hilar nerve-denervated ponies, and they did not differ when external VD or R were added at either the nares or tracheostomy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of verapamil on ventilation and chemical control of breathing in anesthetized rats

The calcium channel blocker, verapamil (0.1-1.0 mg/kg, i.v.) was administered to anesthetized rats to determine its effects on ventilation and on ventilatory responses to hypoxia and CO2. Verapamil produced a dose-dependent increase in tidal volume (VT) and a decrease in respiration rate (f). The bradypnea due to verapamil was characterized by an increase in expiratory duration (TE) and no change of inspiratory duration (TI). Verapamil produced similar changes in VT and f in vagotomized rats. The increase in respiration rate and minute volume due to hypoxia were inhibited by verapamil (0.5 and 1.0 mg/kg) but the increase in tidal volume due to hypoxia was depressed only with the 1.0 mg/kg dose. On the other hand, the increase in VT due to breathing CO2 was not changed by verapamil (0.1-1.0 mg/kg), but depression of the respiratory frequency response to CO2 occurred with 1.0 mg/kg of verapamil. These results indicate that verapamil produced slow, deep breathing and these responses were not mediated by vagal mechanisms. Ventilatory responses to hypoxia were depressed by verapamil. However, since the calcium blocker demonstrated no effect on the VT-CO2 relationship, verapamil did not change ventilatory chemosensitivity to CO2. The data also suggest that mechanisms governing the control of respiratory frequency are more sensitive to verapamil than tidal volume responses.     

Respiratory chemosensitivity during wake and sleep in harbour seal pups (Phoca vitulina richardsii)

In this study, we examined the cardiorespiratory patterns of harbour seal pups under normoxic/normocarbic (air), hypoxic/normocarbic (15%, 12%, and 9% O2 in air), and normoxic/hypercarbic (2%, 4%, and 6% CO2 in air) conditions while awake and sleeping on land. Animals were chronically instrumented to record electroencephalogram (EEG), electromyogram (EMG), and electrocardiogram (EKG) signals, which, along with respiration (whole-body plethysmography) and oxygen consumption (VO2), were recorded from animals breathing each gas mixture for 2-4 h on separate days. Our results show that for animals breathing air, VO2 was not significantly lower during slow-wave sleep (SWS; 7.71 +/- 0.39 mL O2 min(-1) kg(-1); all measurements are mean +/- SEM) than during wakefulness (WAKE; 8.80 +/- 0.25 mL O2 min(-1) kg(-1)) and was unaffected by changes in respiratory drive. Although there was no significant fall in VO2 associated with a decrease in arousal state, breathing frequency (f(R)) did decrease (from 18.80 +/- 1.50 breaths min(-1) in WAKE to 10.40 +/- 0.49 breaths min(-1) in SWS), while the incidence of long apneas (>20 s) increased (12.76 +/- 4.06 apneas h(-1) in WAKE and 31.95 +/- 2.37 apneas h(-1) in SWS). Breathing was rarely seen during rapid eye movement (REM) sleep. Tachypnea was present at all levels of increased respiratory drive; however, hypoxia induced a dramatic bradycardia regardless of arousal state, while hypercarbia produced a tachycardia in SWS only. The hypoxic and hypercarbic chemosensitivities of harbour seal pups were similar to those of terrestrial mammals; however, unlike terrestrial mammals, where hypoxic and hypercarbic sensitivities are often reduced during SWS, the sensitivity of harbour seal pups to hypoxia and hypercarbia remained unchanged during the decrease in arousal state from WAKE to SWS.     

Respiratory adaptations to dead space loading during maximal incremental exercise

We examined the effects of dead space (VD) loading on breathing pattern during maximal incremental exercise in eight normal subjects. Addition of external VD was associated with a significant increase in tidal volume (VT) and decrease in respiratory frequency (f) at moderate and high levels of ventilation (VI); at a VI of 120 l/min, VT and f with added VD were 3.31 +/- 0.33 liters and 36.7 +/- 6.7 breaths/min, respectively, compared with 2.90 +/- 0.29 liters and 41.8 +/- 7.3 breaths/min without added VD. Because breathing pattern does not change with CO2 inhalation during heavy exercise (Gallagher et al. J. Appl. Physiol. 63: 238-244, 1987), the breathing pattern response to added VD is probably a consequence of alteration in the PCO2 time profile, possibly sensed by the carotid body and/or airway-pulmonary chemoreceptors. The increase in VT during heavy exercise with VD loading indicates that the tachypneic breathing pattern of heavy exercise is not due to mechanical limitation of maximum ventilatory capacity at high levels of VT.     

Effects of naloxone on breathing movements during hypercapnia in the fetal lamb

To determine whether endogenous opioids influence the fetal breathing response to CO2 we have investigated the effect of the opiate antagonist, naloxone on the incidence, rate, and amplitude of breathing movements during hypercapnia in fetal lambs in utero. In 20 experiments in six pregnant sheep (130-145 days gestation) hypercapnia was induced by giving the ewe 4-6% CO2-18% O2 in N2 to breathe for 60 min. After 30 min of hypercapnia either naloxone (13 experiments) or saline (7 experiments) was infused intravenously for the remaining 30 min. During hypercapnia breath amplitude increased from 5.8 +/- 0.5 to 9.1 +/- 1.2 mmHg (P less than 0.001), and infusion of naloxone was associated with a further significant increase to 15.7 +/- 1.2 mmHg (P less than 0.001). Naloxone had no effect on the incidence or rate of breathing movements during hypercapnia. After hypercapnia there was a significant decrease in the incidence of fetal breathing movements in the naloxone group (14.7 +/- 3.2%). Infusion of saline during hypercapnia had no effect on incidence, rate, or amplitude of fetal breathing movements. These results suggest that endogenous opioids act to suppress or limit breath amplitude during hypercapnia but do not affect rate or incidence of breathing movements.     

GABA(A) and GABA(B) receptors differentially modulate volume and frequency in ventilatory compensation in obese Zucker rats.

The aim of this study was to investigate whether GABA(A) and/or GABA(B) receptor-mediated mechanisms contribute to the impaired ventilatory response and reduced maximal aerobic exercise capacity in obese Zucker rats. Ten lean and 10 obese Zucker rats were studied at 12 wk of age. Minute ventilation (Ve), tidal volume (Vt), and breathing frequency (f) during room air breathing and in response to 10 min of hypercapnia (8% CO(2)) and 30 min of hypoxia (10% O(2)) were measured by the barometric method, and peak oxygen consumption (Vo(2 peak)) was measured by an enclosed metabolic treadmill following the randomized blinded subcutaneous administration of equal volumes of DMSO (vehicle), bicuculline (selective GABA(A) receptor antagonist, 1 mg/kg), and phaclofen (selective GABA(B) receptor antagonist, 1 mg/kg). Administration of bicuculline and phaclofen to lean animals had no effect on Ve and Vo(2 peak). Similarly, phaclofen failed to alter Ve and Vo(2 peak) in obese rats, although it did significantly increase f after 5-20 min of hypoxia. In contrast, bicuculline increased Ve and Vt relative to DMSO during room air breathing and after 10-30 min of hypoxic exposure in obese rats, but it did not increase Ve at 5 min of hypoxemia. Bicuculline increased Vo(2 peak) relative to DMSO in obese Zucker rats. We conclude that endogenous GABA acting on GABA(A) receptors can modulate Ve and Vo(2 peak) in obese but not in lean Zucker rats, whereas endogenous GABA acting on GABA(B) receptors modulates f during hypoxia (5-20 min) in obese rats in a very different manner from that when acting on GABA(A) receptors.     

Pressure-time product, work rate, and endurance during resistive breathing in humans

We examined the effect of increasing work rate, without a corresponding increase in the pressure-time product, on energy cost and inspiratory muscle endurance (Tlim) in five normal subjects during inspiratory resistive breathing. Tidal volume, mean inspiratory mouth pressure, duty cycle, and hence the pressure-time product were kept constant, whereas work rate was varied by changing the frequency of breathing. There was a linear decrease in Tlim of -2.1 +/- 0.5 s.J-1.min-1 (r = 0.87 +/- 0.06) with increasing work rate. The data satisfied a model of energy balance during fatiguing runs (Monod and Scherrer. Ergonomics 8: 329-337, 1965) and were consistent with the hypothesis that the rate of energy supply, or respiratory muscle blood flow, is fixed when the pressure-time product is constant. Our results indicate that during inspiratory resistive breathing against fatiguing loads, work rate determines endurance independently of the pressure-time product. On the basis of the model, our results lead to estimates of respiratory muscle blood flow and available energy stores under the conditions of our experiment.     

Frequency dependence of respiratory system mechanics during induced constriction in a murine model of asthma.

Airway dysfunction in asthma is characterized by hyperresponsiveness, heterogeneously narrowed airways, and closure of airways. To test the hypothesis that airway constriction in ovalbumin (OVA)-sensitized OVA-intranasally challenged (OVA/OVA) mice produces mechanical responses that are similar to those reported in asthmatic subjects, respiratory system resistance (Rrs) and elastance (Edyn,rs) spectra were obtained in OVA/OVA and control mice during intravenous methacholine (MCh) infusions. In control mice, MCh at 1,700 microg x kg(-1) x min(-1) produced 1) a 495 and 928% increase of Rrs at 0.5 Hz and 19.75 Hz, respectively, 2) a 33% rise in Edyn,rs at 0.5 Hz, and 3) a mild frequency (f)-dependent increase of Edyn,rs. The same MCh dose in OVA/OVA mice produced 1) elevations of Rrs at 0.5 Hz and 19.75 Hz of 1,792 and 774%, respectively, 2) a 390% rise in Edyn,rs at 0.5 Hz, and 3) marked f-dependent increases of Edyn,rs. During constriction, the f dependence of mechanics in control mice was consistent with homogeneous airway narrowing; however, in OVA/OVA mice, f dependence was characteristic of heterogeneously narrowed airways, closure of airways, and airway shunting. These mechanisms amplify the pulmonary mechanical responses to constrictor stimuli at physiological breathing rates and have important roles in the pathophysiology of human asthma.     

Effects of anticipation, prior-exercise, and breathing frequency to ventilatory response during step exercise: a preliminary study.

We examined the effects of anticipation, prior-exercise, and restricted breathing frequency on the ventilatory transient response to bicycle step exercise (75 W, 4 min, 50 rpm), i.e., 1) whether the increase of work rate was anticipated by the subject or not, 2) whether the exercise was preceded by light exercise (25 W), or rest, and 3) whether the exercise entrained the breathing frequency (f: 12.5/min, or 25/min) or not (voluntary). The corresponding step-on exercise was randomly performed at least two to five times by one adult male subject. As a result, a) the initial rapid ventilatory component, phase 1, was not observed when initiated from light exercise, whereas the overshot phase 1 was observed from rest in anticipation and voluntary breathing frequency condition due to the rapid increase of tidal volume; b) compared with the anticipation condition, the phase 1 response of VE in the non-anticipation condition was slower with prior-rest, and not with prior-light exercise; and c) the restriction of the breathing frequency for entraining the exercise rhythm did not affect the initial rapid response, but decreased the fluctuation of VE in the steady state, compared to the condition of voluntary breathing frequency.