Breathing Frequency Response Research Articles

Is breathing frequency a potential means for monitoring exercise intensity in people with atrial fibrillation and coronary heart disease when heart rate is mitigated?

PurposeModerate-intensity aerobic exercise is safe and beneficial in atrial fibrillation (AF) and coronary heart disease (CHD). Irregular or rapid heart rates (HR) in AF and other heart conditions create a challenge to using HR to monitor exercise intensity. The purpose of this study was to assess the potential of breathing frequency (BF) to monitor exercise intensity in people with AF and CHD without AF.MethodsThis observational study included 30 AF participants (19 Male, 70.7 ± 8.7 yrs) and 67 non-AF CHD participants (38 Male, 56.9 ± 11.4 yrs). All performed an incremental maximal exercise test with pulmonary gas exchange.ResultsPeak aerobic power in AF (V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\dot{\ ext{V}}}$$\\end{document}O2peak; 17.8 ± 5.0 ml.kg−1.min−1) was lower than in CHD (26.7 ml.kg−1.min−1) (p < .001). BF responses in AF and CHD were similar (BF peak: AF 34.6 ± 5.4 and CHD 36.5 ± 5.0 breaths.min−1; p = .106); at the 1st ventilatory threshold (BF@VT-1: AF 23.2 ± 4.6; CHD 22.4 ± 4.6 breaths.min−1; p = .240). %V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\dot{\ ext{V}}}$$\\end{document}O2peak at VT-1 were similar in AF and CHD (AF: 59%; CHD: 57%; p = .656).ConclusionWith the use of wearable technologies on the rise, that now include BF, this first study provides an encouraging potential for BF to be used in AF and CHD. As the supporting data are based on incremental ramp protocol results, further research is required to assess BF validity to manage exercise intensity during longer bouts of exercise.

Acute and Chronic Effects of Seizures on Cardiorespiratory Control in the SSKcnj16‐/‐Rat

Epilepsy is a common neurological disorder in which 1/3rd of patients experiences repeated seizures, which puts them at greater risk for Sudden Unexpected Death in Epilepsy (SUDEP). The pathophysiological consequences of repeated seizures resulting in SUDEP, including the effects of repeated seizures on cardiorespiratory function, remain unclear. We previously established a rat model (SSKcnj16‐/‐rats) in which 10 days of repeated daily audiogenic generalized tonic‐clonic seizures (GTCSs) lead to ictal apnea, post‐ictal respiratory suppression, blunted chemoreflexes and high spontaneous mortality (PMID: 33232300). Here we tested the hypotheses that a single GTCS is sufficient to blunt ventilatory chemoreflexes and that repeated seizures lead to progressively greater post‐ictal heart rate (HR) suppression and/or increases in blood pressure (BP). In our pilot experiment, a male SSKcnj16‐/‐rat was implanted with a pressure telemeter and placed in a chronic monitoring plethysmograph to measure breathing and BP/HR continuously for 10 days. The rat was exposed to a 10 kHz sound (2 mins) to elicit a seizure once/day for 10 days. We found that audiogenic seizures led to ictal apneas of variable lengths (4‐25 sec) and ictal asystole (~1‐2 sec), followed by a 31% increase in BP and 30% decrease in HR on days 1‐4. On days 9‐10, there was a 45% increase in BP and 50% decrease in HR, suggesting a progressive effect on HR and BP with repeated seizures. Ongoing studies aim to determine if the ventilatory responses to hypoxia (12% O2) or hypercapnia (7% CO2) are affected 1 hr after recovery from a single GTCS. Naïve SSKcnj16‐/‐rats (n=4, female) were subjected to pre‐ and post‐seizure hypercapnic chemoreflex testing. Relative to room air breathing, minute ventilation (expressed as % of control) increased during hypercapnia before (262% ± 12%) and 1 hr post‐seizure (240% ± 21%). However, breathing frequency responses to hypercapnia 1 hr post‐seizure were reduced (126% ± 6%) compared to before (164% ± 14%), and tidal volume increased to a greater amount post‐seizure (192% ± 13%) compared to before (168% ± 7%), suggesting a significant shift away from a frequency‐mediated to a tidal volume‐mediated chemoreflex response in the post‐ictal period. Our preliminary data suggest that like breathing, repeated seizures may have a progressively negative and acute effect on BP and HR, and that solitary seizures are sufficient to fundamentally alter the hypercapnic ventilatory responses in this rat model, which may have high relevance to human SUDEP.

Type of self-talk matters: Its effects on perceived exertion, cardiorespiratory, and cortisol responses during an iso-metabolic endurance exercise.

Self-talk is an effective mental training technique that has been shown to facilitate or debilitate an athlete's performance, depending on its valence. Although the effects of self-talk have been supported by observing change in sport performance, little is known about how self-talk can induce physiological changes. Specifically, it is important to understand if the type of self-talk (positive, neutral, or negative) and can influence stress-related parameters, such as perceived exertion, cardiorespiratory, and cortisol responses. The study's objective was therefore to investigate the top-down effect of positive and negative self-talk compared to a dissociative activity during an iso-metabolic running exercise on autonomic regulation of cardiorespiratory function. Twenty-nine well-trained male runners [38±13years, 177±7cm and 73±7kg] volunteered to participate in a randomized-group design study that included a negative self-talk (NST), a positive self-talk, and a dissociative group (DG). First, participants underwent an incremental running test on a treadmill to determine the maximal oxygen uptake (V̇O2max ). Next, participants received a mental training session on self-talk and created three positive and three negative self-talk statements. Finally, participants underwent a 60-min steady-state running exercise on a treadmill at 70% of V̇O2max , during which they were cued at 20-, 35-, and 50-min with their personal self-created positive or negative self-talk statements while the DG listened to a documentary. Cardiorespiratory parameters and rate of perceived exertion (RPE) were recorded throughout the 60-min endurance exercise. In addition, salivary cortisol samples were obtained at waking and after treatment. Although oxygen uptake, carbon dioxide production, RPE, and heart rate significantly changed overtime during the 60-min steady-state running exercise, no significant main treatment effect was found. However, RPE scores, minute ventilation, breathing frequency, and salivary cortisol were significantly higher in the NST group compared to the two other groups. These data suggest that NST [emotion-induced stress, as reflected by elevated cortisol] altered the breathing frequency response. In conclusion, manipulating self-talk alters hormonal response patterns, modulates cardiorespiratory function, and influences perceived exertion.

Pontine Parabrachial Nucleus (PBN) Neuron Subtypes Involved With the Control of Breathing Frequency

A subregion within the medial PBN plays a key role in the control of expiratory duration (TE) and breathing frequency (fB) 1. Drug‐induced increases in neuronal activity decrease TE, while depression of these neurons increases TE. Activity from these neurons is relayed with short latencies to neurons in the preBötzinger/Bötzinger region 2. This study analyzed the relationship between charateristics of the discharge frequency (Fn) patterns of I, E, phase spanning and non‐respiratory modulated (NRM) PBN neurons and changes in fB induced by local application of neural transmitter agonist and antagonist. Multichannel neuronal recording with highly localized microinjections into the PBN were performed in decerebrate, vagotomized dogs during isocapnic hyperoxia. The phrenic neurogram was used to assess fB responses and identify neuronal discharge patterns. Plots of fB vs. neuronal Fn during induced fB responses produced by microinjections of AMPA and the GABA‐A receptor antagonist bicuculline (BIC) were linear with high correlation values (r &gt; 0.75). Furthermore, it appears that neurons with little or no respiratory modulation appear to be more highly correlated with fB than neurons with strong phasic patterns, suggesting that these neurons may be responsible for the pontine control of fB.Support or Funding InformationSupported by Department of Veterans Affairs grant 2 I01BX000721‐08 (Zuperku) &amp; R01GM112960‐01A1 (Stucke)Example of breathing frequency response (BPM) to microinjected AMPA (green) in PBN and corresponding neuronal responses (red) for 2 neurons (panel A and panel B). Lower: Plots of BPM vs discharge frequency (Fn = Fmax) for two simultaneously recorded neurons, phasic‐I (A) and NRM (B) with corresponding slope and r‐squared values. Top: Cycle‐Triggered Histograms (CTHs)Figure 1

Arterial blood sampling in male CD-1 and C57BL/6J mice with 1% isoflurane is similar to awake mice

Isoflurane (ISO) is a commonly used anesthetic that offers rapid recovery for laboratory animal research. Initial studies indicated no difference in arterial Pco2 () or pH between conscious (NO ISO) and 1% ISO-exposed CD-1 mice. Our laboratory investigated whether arterial blood sampling with 1% ISO is a suitable alternative to NO ISO sampling for monitoring ventilation in a commonly studied mouse strain. We hypothesized similar blood chemistry, breathing patterns, and cardiovascular responses with NO ISO and 1% ISO. C57BL/6J mice underwent unrestrained barometric plethysmography to quantify the pattern of breathing. Mice exposed to hypoxic and hypercapnic gas under 1% ISO displayed blunted responses; with air, there were no breathing differences. Blood pressure and heart rate were not different between NO ISO and 1% ISO-exposed mice breathing air. Oxygen saturation was not different between groups receiving 2% ISO, 1% ISO, or air. Breathing frequency stabilized at ~11 min of 1% ISO following 2% ISO exposure, suggesting that 11 min is the optimal time for a sample in C57BL/6J mice. Blood samples at 1% ISO and NO ISO revealed no differences in blood pH and in C57BL/6J mice. Overall, this method reveals similar arterial blood sampling values in awake and 1% ISO CD-1 and C57BL/6J mice exposed to air. Although this protocol may be appropriate in other mouse strains when a conscious sample is not feasible, caution is warranted first to identify breathing frequency responses at 1% ISO to tailor the protocol.NEW & NOTEWORTHY Conscious arterial blood sampling is influenced by extraneous factors and is a challenging method due to the small size of mice. Through a series of experiments, we show that arterial blood sampling with 1% isoflurane (ISO) is an alternative to awake sampling in C57BL/6J and CD-1 male mice breathing air. Monitoring breathing frequency during 1% ISO is important to the protocol and should be closely followed to confirm adequate recovery after the catheter implantation.

Dynamic ventilatory responses of females and males to acute isocapnic and poikilocapnic hypoxia

The human ventilatory response during acute hypoxia appears to be biphasic (growth and decay), but the effect of sex on the size and timing of this response is not known. We studied the effects of 15min of poikilocapnic and isocapnic hypoxia (FiO2≈0.10) on ventilation (V˙i) in 14 healthy female and 13 healthy male subjects. Parameters (amplitudes, time delays, time constants) describing individual V˙i responses were estimated using a biexponential function. There were no significant effects of sex on any of these parameters. CO2 regulation significantly altered the amplitudes of growth and decay phases and the onset of the latter phase in females and males. These human data suggest that sex does not affect the biphasic response of ventilation during hypoxia. However, additional evidence in this study suggests that sex influences the breathing frequency response during hypoxia and that this effect depends on the control of CO2.

The effect of rider weight and additional weight in Icelandic horses in tölt: part I. Physiological responses

This study examined the effect of increasing BW ratio (BWR) between rider and horse, in the BWR range common for Icelandic horses (20% to 35%), on heart rate (HR), plasma lactate concentration (Lac), BWR at Lac 4 mmol/l (W4), breathing frequency (BF), rectal temperature (RT) and hematocrit (Hct) in Icelandic horses. In total, eight experienced school-horses were used in an incremental exercise test performed outdoors on an oval riding track and one rider rode all horses. The exercise test consisted of five phases (each 642 m) in tölt, a four-beat symmetrical gait, at a speed of 5.4±0.1 m/s (mean±SD), where BWR between rider (including saddle) and horse started at 20% (BWR20), was increased to 25% (BWR25), 30% (BWR30), and 35% (BWR35) and finally decreased to 20% (BWR20b). Between phases, the horses were stopped (~5.5 min) to add lead weights to specially adjusted saddle bags and a vest on the rider. Heart rate was measured during warm-up, the exercise test and after 5, 15 and 30 min of recovery and blood samples were taken and BF recorded at rest, and at end of each of these aforementioned occasions. Rectal temperature was measured at rest, at end of the exercise test and after a 30-min recovery period. Body size and body condition score (BCS) were registered and a clinical examination performed on the day before the test and for 2 days after. Heart rate and BF increased linearly (P<0.05) and Lac exponentially (P<0.05) with increasing BWR. The W4 was 22.7±4.3% (individual range 17.0% to 27.5%). There was a positive correlation between back BCS and W4 (r=0.75; P=0.032), but no other correlations between body measurements and W4 were found. Hematocrit was not affected by BWR (P>0.05), but negative correlations (P<0.05) existed between body size measurements and Hct. While HR, Hct and BF recovered to values at rest within 30 min, Lac and RT did not. All horses had no clinical remarks on palpation and at walk 1 and 2 days after the test. In conclusion, increasing BWR from 20% to 35% resulted in increased HR, Lac, RT and BF responses in the test group of experienced adult Icelandic riding horses. The horses mainly worked aerobically until BWR reached 22.7%, but considerable individual differences (17.0% to 27.5%) existed that were not linked to horse size, but to back BCS.

Respiratory activation of neurons in the central nucleus of the amygdala (CeA) and effect of CeA neuron stimulation on respiration (1178.5)

Respiratory disease causes aversive responses, which can elicit panic or anxiety. It is known that the central nucleus of the amygdala (CeA) is involved in fear and anxiety emotion, however, the ventilator pattern modulation by CeA is unclear. We hypothesized that tracheal obstruction would elicit activation of CeA neurons and electrical stimulation of within the CeA would cause specific changes in breathing frequency (BF). Tracheal occlusions were applied to anesthetized rats and those rat brains were subsequently sectioned and stained for c‐Fos expression. c‐Fos expressions were found in CeA in the tracheal occlusion group, which suggests that CeA is activated by the mechanical respiratory sensory afferent from the trachea. Micorelectrode electrical stimulation was systematically applied to sites in CeA. The sites with greatest increase and decrease of the BF were identified. The sites with greatest increased BF were located at the rostral part of the dorsal medial border of CeA. The greatest decreased BF responses were observed in the ventral caudal part of CeA. The BF changes after the electrical stimulations indicate that the specific areas of the CeA facilitate or inhibit the respiratory neural drive. The opposite responses found in different CeA sites suggest that the central nucleus of the amygdala can regulate respiratory pattern via multiple pathways.

Enhancement of the breathing frequency response to hypoxia by neonatal caffeine treatment in adult male rats: The role of testosterone

Caffeine is a common treatment for apnea of prematurity. Although relatively safe, little is known about the potential long-term effects of this treatment on respiratory control development. We previously showed that adult male (but not female) rats previously subjected to neonatal caffeine treatment (NCT; 15 mg/kg/day, postnatal days 3-12) show a higher breathing frequency response during the early phase of hypoxic exposure. To address the role of sexual hormones in this sexual dimorphism, the present study tested the hypothesis that in adult male rats, circulating testosterone contributes to NCT-related augmentation of the acute breathing frequency response to hypoxia. Whole body plethysmography was used to compare the acute ventilatory response to moderate hypoxia (FIO2=0.12; 20 min) between rats previously subjected to NCT or neonatal water treatment (NWT; same treatment as NCT but using water). In each group, rats were either sham-operated or gonadectomized (GDX) 14 days prior to ventilatory measurements. In sham-operated rats, the increase in breathing frequency measured during the first 8 min of hypoxia was greater in NCT rats versus NWT. The hypoxic ventilatory response measured at the end of the hypoxia was not affected by treatment, thus indicating that NCT mainly affected the peripheral component of the chemoreflex. Gonadectomy had no effect on NCT but augmented the frequency response of NWT rats to the same level of NCT, thus eliminating the between-group difference. NCT may interfere with the inhibitory effect of circulating testosterone on carotid body function. Although appealing, additional experiments are necessary to substantiate this interpretation.

Neonatal caffeine induces sex-specific developmental plasticity of the hypoxic respiratory chemoreflex in adult rats

Caffeine is widely used to treat apneas of prematurity during the neonatal period; however, the potential consequences of administering a neonatal caffeine treatment (NCT) during a critical period for respiratory control development are unknown. The present study therefore determined whether NCT in rats alters the hypoxic respiratory chemoreflex measured at adulthood. Newborn rats received either caffeine (15 mg/kg) or water (control) each day from postnatal day 3 to 12. The ventilatory response to a hypoxic challenge (inspired O(2) fraction = 0.12) was first evaluated in awake adult female and male rats using whole body plethysmography. Results showed that NCT increased the initial phase of the breathing frequency response to hypoxia in males only. This result was confirmed in anesthetized and artificially ventilated adult male rats where NCT also increased the phrenic burst frequency response to hypoxia. RT-PCR assessment of mRNA encoding for adenosine A(1A) and A(2A) receptors, dopamine D(2) receptors, and tyrosine hydroxylase in the rat carotid bodies showed that NCT enhanced mRNA expression levels of adenosine A(2A), dopamine D(2) receptors, and tyrosine hydroxylase of males but not females. Subsequent experiments on awake male rats showed that injection of the adenosine A(2A) receptor antagonist ZM2413855 (1 mg/kg ip) before ventilatory measurements abolished, in NCT rats, the enhanced respiratory frequency response observed during the early phase of hypoxia. We propose that NCT elicits a sex-specific increase in the hypoxic respiratory chemoreflex, which is related, at least partially, to an enhancement in adenosine A(2A) receptors in the rat carotid body.

Chronic corticosterone elevation and sex‐specific augmentation of the hypoxic ventilatory response in awake rats

Perinatal stress disrupts normal development of the hypothalamo-pituitary-adrenal (HPA) axis. Adult male (but not female) rats previously subjected to a stress such as neonatal maternal separation (NMS) are characterized by chronic elevation of plasma corticosterone (Cort) levels and an abnormally elevated hypoxic ventilatory response through mechanisms that remain unknown. The present study tested the hypothesis that a chronic increase of plasma Cort levels alone augments the ventilatory response to hypoxia in adult rats. Three groups of Sprague-Dawley male and female rats were used (control, placebo and Cort implants). Rats subjected to chronic Cort elevation received a subcutaneous Cort implant (300 mg) 14 days prior to ventilatory measurements, whereas sham-operated rats received placebo implants. Controls received no treatment. Plasma Cort levels and body weight profiles were measured to assess protocol efficiency. Whole body plethysmography was used to measure ventilatory activity and metabolic indices during normoxia and following a 20 min period of moderate hypoxia (12% O(2)). Male rats implanted with Cort showed a ventilatory response to hypoxia higher than placebo-treated rats; this effect was mainly due to a larger tidal volume response. In females, Cort treatment increased the breathing frequency response but the effect on minute ventilation was not significant. Taken together, these data show that chronic elevation of Cort alone increases the ventilatory response to hypoxia, but in a sex-specific manner. These data raise important questions regarding the mechanisms underlying the sexual dimorphism of this effect and the potential link between HPA axis dysfunction and respiratory disorders related to abnormal ventilatory chemoreflex.

Neonatal caffeine augments the acute breathing frequency response to hypoxia and the adenosine and the dopamine receptor mRNA expression in the carotid body of adult rats

Neonatal caffeine treatment (NCT), used to treat apnea of prematurity, increases persistently the hypercapnic ventilatory response of adult rats. However, the influence of NCT on the ventilatory response to hypoxia is unknown. The aim of this study was to determine the consequences of NCT on 1) the ventilatory response to hypoxia (12% of O2) of adult male and female rats and 2) the tyrosine hydroxylase, the adenosine, and the dopamine receptor mRNA expression in the carotid bodies. To this aim, plethysmographic measurements were performed on male and female adult rats previously subjected to either water (control) or caffeine 15 mg/kg (NCT) administration during the neonatal period (postnatal days 3 to 12). Tyrosine hydroxylase, adenosine, and dopamine receptor mRNA quantification in the carotid bodies was estimated by RT-PCR also. NCT enhanced the immediate frequency response on the onset of hypoxia in a sex-specific manner (male only). Results of RT-PCR analysis showed that NCT augments tyrosine hydroxylase, adenosine A2A and dopamine D2 receptor mRNA expression in the carotid bodies of males, but not of females. Thus, the sex-specific increase of the hypoxic ventilatory response induced by NCT could be due to an increase of adenosine A2A and/or dopamine D2 receptor expression observed only in the carotid bodies of males. Supported by the Foundation for the Research into Children's Disease, and the Jeanne-and-Jean-Louis-Levesque’ Chair in Perinatalogy.

Tidal volume and breathing frequency responses to poikilocapnic and isocapnic hypoxia in humans

The acute response to hypoxia in humans has been reported to arise predominately from increases in tidal volume (VT) with negligible changes in breathing frequency (fB). The effect of arterial CO2 on this response has not been described. We examined the ventilatory contributions of VT and fB to the hypoxic response under both poikilocapnic (PH) and isocapnic (IH) conditions in 10 normal adults (26 ± 4 yrs, mean ± SD). During IH, PETCO2 was held constant at 37 ± 2.0 Torr (1 Torr above resting values) while PETO2 was reduced stepwise to 45 Torr using the technique of dynamic end-tidal gas forcing. During PH, PETO2 was reduced stepwise to 45 Torr while PETCO2 was uncontrolled (i.e. zero inspired CO2). Hypoxia was maintained for 20 minutes, and tests were separated by 1 hour. Peak ventilation (VE), was significantly higher during IH (49.8 ± 14.3 L·min−1) compared to PH (24.1 ± 7.7 L·min−1, P < 0.001). During IH, peak VE was mediated by increases in both VT (1.0 ± 0.4 to 2.2 ± 0.5 L, P < 0.001) and fB (14.7 ± 4.6 to 19.2 ± 4.5 breaths·min−1, P < 0.05), while during PH peak VE was mediated by increased VT (0.8 ± 0.2 to 1.5 ± 0.4 L, P < 0.01) with no change observed in fB. At the termination of both IH and PH, a significant frequency undershoot was observed (20 ± 23 %, P < 0.05 and 22 ± 22 %, P < 0.01 respectively), previously documented only in animals. These data demonstrate a role of arterial CO2 in the development of a fB response to hypoxia, though whether this is due to CO2 per se or the magnitude of peak VE remains unknown. We have also documented a significant post hypoxic frequency decline not previously reported in humans occurring during both conditions. This study was approved by the local Ethics board and supported by AHFMR, HSFA and CIHR.

Breathing Patterns Associated with Trait Anxiety and Breathlessness in Humans

Idiopathic hyperventilation (IH) is a condition of uncertain aetiology characterized by sustained arterial and alveolar hypocapnia and a plethora of symptoms, the most commonly reported being shortness of breath, and breathlessness. We previously reported that anxiety increases respiratory frequency and minute ventilation with no change in metabolism in normal subjects. In this study, we compared the breathing frequency response to 5% and 7% of CO(2) gas mixtures in normal subjects (n = 13) and in subjects with IH (n = 9), taking into account anxiety and breathlessness in order to determine how breathing patterns may vary with changes in the degree of involvement of higher brain centers because of anxiety and the perception of breathlessness. CO(2) produced a significantly higher value in respiratory frequency (f) in subjects with IH. Subjects with IH also showed lower P(ET)CO(2) than normal subjects. During the inhalation of room air, a significant correlation between f and trait anxiety scores was observed in normal subjects (r = 0.49) and IH subjects (r = 0.69). However, the IH group showed no significantly higher trait anxiety in comparison with normal subjects. There was a significant correlation between the level of perceived breathlessness and f during the inhalation of 5% and 7% CO(2), even during the inhalation of room air in IH subjects. This study suggests that an excessive increase in f in subjects with IH may be due to the interaction of two factors, trait anxiety and breathlessness.

ARTERIAL OXYGEN SATURATION DURING MAXIMAL EXERCISE DEPENDS ON CAPACITY TO INCREASE VENTILATION

1660 The capacity of the healthy pulmonary system has traditionally been considered too large to limit exercise. The observation of exercise-induced hypoxemia (EIH) in some highly trained athletes has led to reevaluation of pulmonary performance during exercise. In order to examine the relationship between ventilatory response to exercise and the maintenance of arterial oxygen saturation (SaO2), nine highly trained collegiate male runners (VO2max, 72.1, s.d. 4.4 ml*kg−1*min−1) performed a progressive treadmill test to maximal exercise. Flow-volume loops, metabolic data, and end-tidal gas samples were collected during the penultimate and final stages of exercise. All subjects displayed EIH (SaO2, 88.8, s.d. 1.8%). The extent of expiratory flow limitation varied (range 0.0 - 42.6% flow limited). SaO2 at maximal exercise was inversely related to the change in FETCO2 with the final work increase (r = −0.72) and the change in VE/VCO2 (r = 0.81). The breathing frequency response to the final work increase was inversely related to the change observed in FETCO2 (r = −0.79), and directly related to the changes in VE/VCO2 (r = 0.78) and SaO2 at end exercise (r = 0.66). Also, there was a relationship between the change in degree of expiratory flow limitation and the decline in SaO2 (r = −0.84). Within our sample, relationships are evident among the extent of expiratory flow limitation, the ability to increase breathing frequency, and end exercise arterial desaturation. This suggests that some athletes ventilate at their maximal ventilatory capacity and further increases in ventilation are not possible.

Ventilatory and arousal responses to hypoxia and hypercapnia in a canine model of obstructive sleep apnea.

We have previously described a canine model of obstructive sleep apnea (OSA) in which sleep-wake state is monitored continuously by a computer that produces tracheal occlusion when sleep occurs. Our aim was to assess the effects of long-term application of this model on resting ventilation and on the ventilatory and arousal responses to hypercapnia and hypoxia. Five dogs were maintained on the model for 15.5 +/- 1.7 (mean +/- SE) wk, with a mean apnea index of 57.5 +/- 4.5 occlusions/h of sleep. Resting ventilation and the ventilatory and arousal responses to progressive hypoxic and hypercapnic rebreathing were assessed during wakefulness (W) and both slow-wave (SWS) and rapid-eye-movement (REM) sleep at baseline prior to intervention, at the end of the OSA phase, and following a 1 to 3-mo recovery period. During the period of OSA there were small changes in respiratory timing at rest, but no significant changes in PCO2 or SaO2. As compared with baseline, the ventilatory response to hypoxia during OSA was strikingly reduced during W, and significantly although less markedly reduced during SWS and REM. The reduction was due to a decreased breathing frequency response to hypoxia. In addition, during OSA there was a significant decrease from baseline in SaO2 at arousal during hypoxic rebreathing in both SWS and REM. All responses returned to normal during recovery. In contrast to hypoxia, hypercapnic ventilatory responses during OSA were slightly increased over their baseline values both in W and SWS, owing to a leftward shift of the ventilation-versus-PCO2 relationship. During recovery, these responses reverted partly to baseline for W and reverted completely to baseline for SWS. There were no significant changes in arousal PCO2 during hypercapnic rebreathing in either SWS or REM across the pre-OSA baseline, OSA, and post-OSA recovery periods. We conclude that long-term application of the OSA model is associated with a selective, reversible decrease in ventilatory and arousal responses to hypoxia.

Breathing pattern and ventilatory response to CO2 during exercise.

The aim of this study was to determine during moderate exercise whether response to the CO2 rebreathing test was dependent on differences in breathing pattern components among individuals recorded before the test and whether differences in tidal volume response and/or breathing frequency response to CO2 during the test could influence their ventilatory response to CO2. Ten healthy, sedentary male subjects, 20 to 34 years old, participated in the study. Ventilatory response to CO2 was measured by the CO2 rebreathing method (7% CO2, 50% O2). The measurements of breathing pattern components and CO2 rebreathing were made during mild steady state exercise: VCO2 = 20 ml.kg-1.min-1. We measured the following: 1) tidal volume (VTex) and breathing frequency (fex) before CO2 rebreathing and 2) ventilatory response to CO2 (SVEex), tidal volume response to CO2 (SVTex), and breathing frequency response to CO2 (Sfex) during the CO2 rebreathing test. The results showed that SVEex was correlated with VTex (r = 0.89, p less than 0.001), fex (r = -0.79, p less than 0.01), and Sfex (r = 0.83, p less than 0.01). There was no correlation between SVEex and SVTex. A curvilinear relationship existed between SVEex and alveolar ventilation calculated during exercise (r = 0.87, p less than 0.001), but there was no correlation with dead space. Sfex was positively correlated with VTex (r = 0.68, p less than 0.05) and negatively with fex (r = -0.70, p less than 0.05). We concluded that, during moderate exercise, higher tidal volumes measured before CO2 rebreathing were associated with higher response to the CO2 rebreathing test and consequently with higher ventilatory response to CO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Interrelationships among airway CO2, airway pressure, and breathing frequency.

The breathing frequency response to changes in airway CO2 of a vascularly isolated lobe of the canine lung has previously been shown to be primarily dependent on CO2-mediated changes in airway pressure. This study was carried out to determine what contribution changes in airway pressure make in the whole lung airway CO2-mediated breathing frequency response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. Diaphragm electromyogram (EMG) was used to monitor respiratory center output and to trigger ventilation of the lungs. Isoproterenol administered to the lungs prevented hypocapnic airway constriction but only partially blocked the decrease in breathing frequency, suggesting that in the whole lung preparation, airway CO2 in part alters breathing frequency through a direct effect on pulmonary receptors. At constant positive end-expired pressures (1-6 Torr), 0% airway CO2 produced greater increases in expiratory time than 10% CO2. Thus airway CO2 can affect breathing frequency in the absence of CO2-related changes in airway pressure at pressures that would produce lung volumes similar to those observed at end expiration in the intact animal. An argument is presented that the receptors directly affected by CO2 are probably not located in the airways constricted by hypocapnia.

Changes in rib cage and diaphragm contribution to ventilation after morphine.

Ventilatory response to CO2 was measured before and after intravenous morphine, 0.15 mg/kg, in 13 healthy adult subjects. Tidal volume response was partitioned into that component due to rib cage (RC) and that due to abdomen-diaphragm motion (AD). The response was assessed also in terms of inspiratory and expiratory durations (Ti, Tc), the ratio of T; to total cycle duration (Ti/Ttot) and mean inspiratory flow (VT/Ti). The ventilatory response to CO2 was displaced to the right after morphine; this was due to a decrease in both the tidal volume and breathing frequency responses. The displacement of the tidal volume response was due largely to a similar displacement of the RC response; there was no significant change in the AD response. The decrease in the frequency response after morphine was manifest by increases in both inspiratory and expiratory durations at equivalent CO2 pressures during rebreathing; these increases occurred to equivalent extents such that no change of Ti/Ttot was found during re-breathing after morphine. Mean inspiratory flow per breath was significantly reduced during rebreathing after morphine. When RC, AD, Ti, Te, VT/Ti, and Ti/Ttot during rebreathing were plotted as functions of tidal volume and expressed as a per cent of vital capacity, no effect was found after morphine. The marked depression of the RC response and the relative stability of the AD response after such dissimilar ventilatory depressants as morphine and halothane may represent characteristic responses of the separate groups of intercostal and phrenic motoneurones to descending influences determined by the direct action of these drugs on respiratory neurons in the medulla.

Location of lung receptors mediating the breathing frequency response to pulmonary CO 2

Pulmonary stretch receptors are thought to mediate the breathing frequency (bf) response to changes in pulmonary CO 2. However, the location and distribution of these receptors is disputed. The purpose of this study was to determine what contribution the extrapulmonary receptors make in the pulmonary CO 2 bf response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. The diaphragm electromyogram was used to monitor respiratory center output and to trigger a ventilator. Exposure of an upper airway segment to CO 2 or positive end-expired pressure failed to produce changes in the bf. Denervation of the upper airway down to but not including the hilum caused similar insignificant changes in the CO 2 bf response. Lungs collapsed by suction showed minimal Hering-Breuer inhibition when compared with inflated lungs. Bronchial arterial perfusion with hypocapnic followed by hypercapnic blood failed to produce changes in the bf while similar perfusion of the pulmonary arterial system resulted in significant increases in bf. It appears that the receptors mainly responsible for the pulmonary CO 2 response are located in the more peripheral regions of the lung.