Ventilatory control after pulmonary resection

Because pulmonary resection decreases pulmonary compliance, the effects of resection on ventilation might be similar to the known effects of elastic loading. We evaluated the breathing pattern and ventilatory drive in 12 patients before and after pulmonary resection with mean tissue loss of 4 segments. During resting ventilation, the only significant change after resection was a decrease in inspiratory time (Tl). At a higher level of minute ventilation (VE), induced by CO2 rebreathing, significant changes included increased respiratory frequency, decreased tidal volume and Tl, and increased occlusion pressure (P0.1). Both ventilation and occlusion pressure responses to CO2 (delta VE/delta PACO2, delta P0.1/delta PACO2) were unchanged after resection. We conclude that increased ventilation induced by CO2 rebreathing unmasks a breathing pattern after pulmonary resection which is similar to that seen with breathing against an external elastic load.     

Regulation of ventilation before and after sleep in patients with obstructive sleep apnoea

The objective was to examine whether abnormal breathing during sleep may affect regulation of ventilation after awakening in patients with obstructive sleep apnoea (OSAS). In 19 patients with OSA and 12 normal subjects we examined ventilatory responses to hypoxia (HVR) and to hypercapnia (HCVR) before and after sleep (BS and AS), and compared the changes in ventilatory responses with respiratory events during sleep. In the OSA group, the values of resting ventilation were significantly smaller in AS than those in BS and end-tidal partial pressure of CO2 in arterial blood (Pco2) (PETCO2) rose significantly from BS to AS. The slopes of the HVR or HCVR did not differ between BS and AS. However, both the response lines shifted downward and minute ventilation (VE)80 (VE at arterial oxygen saturation (Sao2) of 80%) in HVR and VE60 (VE at PETCO2 of 60 mmHg) in HCVR decreased significantly from BS to AS. The percentage changes of VE80 and VE60 were significantly correlated with mean Sao2, total sleep time below Sao2 of 90% and lowest Sao2 during sleep. However, in normal subjects we observed no circadian variation in their ventilatory responses. These data support the hypothesis that repeated episodes of nocturnal hypoxia and hypercapnia may modify the regulation of ventilation after awakening in patients with OSA.     

阻塞性睡眠呼吸暂停综合征患者睡眠状态下呼吸中枢控制功 …

目的 探讨阻塞性睡眠呼吸暂停综合征（ＯＳＡＳ）患者上气道阻塞与睡眠状态下呼吸中枢控制功能的低下是否有关，方法 通过经鼻气管插管建立鼻咽通气道测定了１６例重度ＯＳＡＳ患者在清楚状态，非快动眼（ＮＲＥＭ）Ｉ＋Ⅱ睡眠期，Ⅲ＋Ⅳ睡眠期，快速眼（ＲＥＭ）睡眠期的口腔阻断压（Ｐ０．１）低氧反应指标（△Ｐ０．１／△ＳａＯ２，△ＶＥ／△ＳａＯ２）及高二氧化碳反应指标（△Ｐ０．１／△ＳａＯ２，△ＶＥ／△ＳａＯ２）。     

Hypnosis effect on carbon dioxide chemosensitivity

Hypnosis is an induced state of heightened suggestibility during which certain physiologic variables can be altered. To investigate if carbon dioxide (CO2) chemosensitivity could be blunted during this suggestible state, we measured hypercapnic ventilatory response (HCVR, delta VE/delta PaCO2), oxygen consumption (VO2), breathing pattern (VT and f), inspiratory flow rate (VT/Ti), and inspiratory timing (Ti/Ttot) in 20 healthy subjects. Mouth occlusion pressures (P0.1) were measured in the last nine subjects. Resting oxygen consumption and minute ventilation were measured during awake and hypnotic control states. The HCVR was measured spontaneously and with the suggestion to maintain normal ventilation during both awake and hypnotic conditions. It was found that without a change in metabolism, ventilatory responses to CO2 could be blunted both voluntarily, and to a greater degree, with hypnotic suggestion. These findings may have important implications in clinical settings in which patients suffer from marked dyspnea secondary to increased ventilatory chemosensitivity.     

阻塞性睡眠呼吸暂停低通气综合征患者呼吸调节的家族聚集性研究

目的　探讨呼吸调节异常是否是引起阻塞性睡眠呼吸暂停低通气综合征 (OSAHS)家族聚集性的原因。方法　对 10例重度OSAHS患者、其一级亲属 16名及单纯肥胖者 14例进行睡眠监测并测定低氧通气反应 (HVR)、高碳酸通气反应 (HCVR)。对OSAHS患者进行持续气道正压通气(CPAP)治疗 ,在治疗的第 1、2、3个月复查HVR和HCVR。结果　 (1)OSAHS患者亲属的呼吸暂停及低通气指数 (AHI)为 (2 8 4± 39 1)次 /h ,出现习惯性打鼾、白天嗜睡的比例分别为 10 0 %和 90 % ,与对照组相比明显增高 (分别为P <0 0 5 ,P <0 0 1,P <0 0 1)。 (2 )亲属中无论是否有OSAHS ,其HVR、HCVR分别为 (- 19± 2 4 )cmH2 O、(0 31± 0 35 )cmH2 O/mmHg ,与对照组比较差异无显著性 (P >0 0 5 )。 (3)经CPAP治疗后 ,OSAHS患者的HVR、HCVR恢复正常。结论　OSAHS有家族聚集性 ,但这一聚集性与遗传性呼吸调节异常无关     

Respiratory stimulants and sleep periodic breathing at high altitude. Almitrine versus acetazolamide

We studied the effects of almitrine, acetazolamide, and placebo on the hypoxic ventilatory response (HVR), sleep periodic breathing, and arterial oxygen saturation (SaO2) in 4 healthy climbers. In a laboratory on Denali (Mt. McKinley) at 4,400 m (PB = 440 mm Hg), we used a double-blind, randomized, three-way crossover design. The HVR was measured during the waking state. Periodic breathing and SAO2% were measured during 3-h sleep studies. Almitrine and acetazolamide both increased SaO2% during sleep, although almitrine increased periodic breathing, whereas acetazolamide decreased periodic breathing. The HVR (delta VE/delta SaO2%) was doubled with almitrine (p less than 0.05), but unchanged with acetazolamide. The HVR was positively related to periodic breathing (p less than 0.05). We conclude that periodic breathing during sleep at high altitude is related to the hypoxic ventilatory response, and that acetazolamide is a superior agent to almitrine for ameliorating periodic breathing.     

Ventilatory and P0.1 response to hypercapnia in quadriplegia.

Unlike individuals with comparable degrees of respiratory muscle weakness from other causes, quadriplegic patients have a blunted ventilatory and P0.1 response to hypercapnia. This suggests that the diminished response in quadriplegia is due, in part, to an alteration in respiratory drive. We measured the hypercapnic response in 9 subjects with chronic quadriplegia (Q) and 8 normal controls (N). Ventilatory muscle strength, maximum voluntary ventilation (MVV), and lung volumes were measured in all subjects. The ventilatory response (HCVR) in Q was significantly less than in N (0.73 +/- 0.37 vs 2.95 +/- 0.4 L.min-1.mmHg-1; P less than 0.001), even when normalized for indices of respiratory muscle performance (e.g., vital capacity, MVV). There was no significant change in the HCVR in Q after the administration of naloxone. We also serially studied 2 subjects with acute quadriplegia, and found that despite progressive improvement in respiratory muscle performance, there was no accompanying increase in the response to hypercapnia. These data suggest that muscle weakness alone cannot explain the blunted hypercapnic response in quadriplegia, and are consistent with the hypothesis that these subjects have a reduced ventilatory drive.     

Learning effect of repeated hypercapneic ventilatory response testing

To determine whether hypercapneic ventilatory response (HCVR) is affected by repeated testing, the HCVR of 22 healthy subjects was determined daily for 4 consecutive days. The slope (S) of the HCVR increased to a maximum on Day 3, which was 14% greater than S on Day 1 (p less than 0.05). The increase in airway occlusion pressure during progressive hypercapnea (delta P0.1/delta PCO2) showed no significant change, indicating that although S and delta P0.1/delta PCO2 are both good measurements of ventilatory response, they are not totally interchangeable in normal subjects. A subgroup of 12 subjects (termed "increasers") was responsible for the overall increase in S. For this subgroup, S was significantly smaller on Day 1 than on each subsequent day. Increasers also had a significantly greater value of S on each day of the study than subjects who did not increase ("decreasers"). On Day 1, increasers' S was 3.77 +/- 1.31 L min-1 mm Hg-1, while decreasers' S was 2.46 +/- 1.00 (p less than 0.001). Some normal subjects demonstrate a learning effect during repeated daily testing of HCVR by the rebreathing technique, and those subjects whose S increases are those with large initial values of S.     

Hypercarbic ventilatory responses of human heart-lung transplant recipients

To evaluate the effects of chronic pulmonary denervation on ventilatory control, we compared the hypercarbic ventilatory responses (HCVR) of 12 human heart-lung transplant recipients (HL) and 24 normal control subjects (C). The six male HL were subsequently compared with eight male heart transplant recipients (H), as well as the 12 male C. All subjects had normal spirometry, but lung volumes of both transplant groups were somewhat less than those of C. The HCVR of HL and C were indistinguishable (2.68 +/- 0.28 versus 2.71 +/- 0.22 L/min/mm Hg, respectively). The increment of mouth occlusion pressure (delta Pm0.1/delta CO2), however, was markedly greater in HL (P much less than 0.01). The three male groups also had equivalent HCVR, and again, the HL had an increased delta Pm0.1/delta CO2. HL men exhibited larger increments of VT and decreased frequency responses during CO2 rebreathing than did male C and H, although these differences were statistically significant only in the comparison between the transplant groups. We conclude that HL with normal spirometry have appropriate HCVR, despite pulmonary denervation. Pm0.1 responses of these subjects are increased, however, reflecting either a compensatory response to greater respiratory impedances or an occult alteration of ventilatory mechanics. Moreover, compared with subjects with similar pulmonary function, e.g., heart transplant recipients, the breathing pattern of HL during progressive hypercarbia is consistent with the absence of vagal-mediated inflation inhibition.     

Effects of posture on stimulated ventilation in quadriplegia

Quadriplegics are able to compensate for alterations of operational length of the diaphragm by reflexly increasing neural drive to the diaphragm. This increase in neural drive is adequate to maintain required tidal volume and minute ventilation during quiet breathing in these patients with limited inspiratory muscle function. It is not known, however, if this neural compensation is sufficient to preserve ventilation when the diaphragm is stressed by simultaneously changing its operational length and increasing ventilatory demands. This issue was explored in 7 quadriplegics whose vital capacity was reduced to 15 to 53% of predicted. The diaphragm was stressed by shortening its length from the supine to a 60 degree tilted position, and also by inducing hyperventilation by having the subjects rebreathe 7% CO2. Response to this stress was recorded by monitoring the ventilatory response to rebreathing CO2 (delta VE/delta PCO2), and also by measuring mouth pressure 0.1 s after occluding the airway at the start of inspiration during CO2 rebreathing (delta P0.1/delta PCO2). A change from the supine to the tilted position caused an increase in resting end-expiratory volume of 0.8 +/- 0.2 L (SD) and therefore shortened the diaphragm. Despite this shortening of diaphragm length and the stress of CO2 rebreathing, there was no significant change in delta VE/delta PCO2 and delta P0.1/delta PCO2 with changes in posture. The delta VE/delta PCO2 was 0.82 +/- 0.42 L/min/mm Hg supine versus 0.95 +/- 0.65 L/min/mm Hg when tilted. The delta P0.1/delta PCO2 was 0.18 +/- 0.08 cm H2O/mm Hg supine versus 0.20 +/- 0.10 cm H2O/mm Hg tilted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of protriptyline on ventilatory responses to hypercapnia and asphyxia in normal subjects

A double-blind crossover study was undertaken to assess the effect of protriptyline on ventilatory responses in normal subjects. Seven subjects received in random order placebo, 10 mg and 20 mg protriptyline daily for 2 weeks. Measurements of hypercapnic ventilatory response (HCVR) and asphyxial hypoxic ventilatory response (HVR) were made before treatment, 6-8 h after the first dose, and after 2 weeks treatment. Mean HCVR and HVR following 10 mg and 20 mg protriptyline did not differ significantly from measurements on placebo, neither for the single dose study or after 2 weeks.     

Effect of hypoxia on the sensation of dyspnea during hypercapnic ventilatory response in normal subjects]

We examined, in 32 normal adults, the effect of hypoxia on the sensation of dyspnea during hypercapnic ventilatory response (HCVR). The tests were conducted under two different levels of inspiratory O2 content, either hyperoxia (PETO2 greater than 150 Torr) or hypoxia (PETO2 50-55 Torr), with simultaneous assessment of dyspnea sensation by visual analogue scaling (VAS). The sensation was evaluated either in relation to VE standardized by predicted MVV (the slope of VAS-VE regression line or VAS at VE 40%) or in relation to PETCO2 (the slope of VAS-PETCO2 line or VAS at PETCO2 55 Torr). Concomitant hypoxia significantly enhanced both the mean value of delta VE/delta PETCO2 and that of delta P0.1/delta PETCO2. The sensation of dyspnea did not differ between the two conditions when it was evaluated in relation to ventilation, whereas it was markedly greater during hypoxic HCVR when it was evaluated in relation to PETCO2. The hypoxic augmentation of the sensation, compared at PETCO2 55 Torr, could be explained by increase of the motor output from the respiratory center, since it was positively correlated with the relative change of VE, VTTI, and delta P0.1/delta PETCO2 (r = 0.70, p less than 0.0001; r = 0.63, p less than 0.0001; r = 0.40, p less than 0.05, respectively). From these findings, we conclude that hypoxia does not have a direct dyspnogenic effect, at least in normal subjects.     

Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients

RATIONALE: Methadone is a long-acting mu-opioid and is an effective treatment for heroin addiction. Opioids depress respiration, and patients receiving methadone maintenance treatment (MMT) have higher mortality than the general population. Few studies have investigated ventilatory responses to both hypercapnia and hypoxia in these patients. STUDY OBJECTIVES: We measured hypercapnic ventilatory response (HCVR) and hypoxic ventilatory response (HVR) and investigated possible factors associated with both in clinically stable patients receiving MMT. DESIGN AND SETTING: Patients receiving long-term, stable doses of methadone recruited from a statewide MMT program, and normal, non-opioid-using subjects matched for age, sex, height, and body mass index were studied with HCVR and HVR. RESULTS: Fifty MMT patients and 20 normal subjects were studied, and significantly decreased HCVR and increased HVR were found in MMT patients compared to normal subjects (HCVR [mean +/- SD], l.27 +/- 0.61 L/min/mm Hg vs 1.64 +/- 0.57 L/min/mm Hg [p = 0.01]; HVR, 2.14 +/- 1.58 L/min/% arterial oxygen saturation measured by pulse oximetry [Sp(O2)] vs 1.12 +/- 0.7 L/min/% Sp(O2) [p = 0.008]). Respiratory rate and not tidal volume changes were the major physiologic responses contributing to both HCVR and HVR differences between the groups. Variables associated with HCVR in the MMT patients are as follows: obstructive sleep apnea/hypopnea index (t = 5.1, p = 0.00001), Pa(CO2) (t = - 3.6, p = 0.001), body height (t = 2.6, p = 0.01) and alveolar-arterial oxygen pressure gradient (t = 2.5, p = 0.02). Variables associated with HVR in MMT patients are body height (t = 3.2, p = 0.002) and Pa(CO2) (t = - 2.8, p = 0.008). CONCLUSIONS: Stable long-term MMT patients have blunted central and elevated peripheral chemoreceptor responses. The mechanisms and clinical significance of these findings need further investigation.     

The respiratory neuromuscular response to hypoxia, hypercapnia, and obstruction to airflow in asthma.

In chronic obstructive pulmonary disease (COPD), the neuromuscular response to an acute increase in airflow produced by external flow resistive loads (FRL) is impaired. The present study compared the response to FRL of 15 subjects with airway obstruction due to asthma and that of 15 normal subjects. FRL were applied during progressive hypercapnia and isocapnic hypoxia produced by rebreathing techniques to permit the response to be assessed at the same degree of CO2 or O2 drive. The neuromuscular response to FRL was assessed from the airway occlusion pressure developed 100 msec after the onset of inspiration (P100), as well as ventilation. During control rebreathing, ventilatory responses to hypercapnia (ratio of change in minute ventilation to change in PCO2, delta VE/delta PCO2) and hypoxia (ratio of change in VE to the change in percentage of O2 saturation, delta VE/deltaSO2) were the same in asthmatic and normal subjects despite differences in the mechanics of breathing. The P100 response to hypercapnia delta P100/delta PCO2) and hypoxia (delta P100/delta SO2) as well as absolute P100 at any given degree of O2 and CO2 drive was greater during control rebreathing in asthmatics than in normal subjects (P less than 0.05). FRL values of 9 and 18 cm H2O per L per sec applied during either hypercapnia or hypoxia increased the occlusion pressure to a greater extent in asthmatics than in normal subjects. Methacholine-induced bronchoconstriction was used to test the effect of acute airway obstruction on the response to FRL. Bronchoconstriction was associated with an increase in the P100 response to hypercapnia and to FRL, despite increases in lung volume and decreases in inspiratory muscle force. We conclude that: (1) asthmatics with airway dysfunction have an increased nonchemical drive to breathe mediated at least in part by sensory receptors in the airways; (2) asthmatics with airway obstruction respond supernormally to acute changes in resistance to airflow, unlike subjects with COPD. The failure of COPD subjects with prolonged airway obstruction to respond to FRL may be due to adaptation of the sensory mechanisms that respond to changes in airway resistance.     

Ventilatory response to 2-h sustained hypoxia in humans

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

阻塞性睡眠呼吸暂停低通气患者的呼吸调节

目的观察阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者的呼吸调节.方法 OSAHS组肥胖OSAHS患者35例,根据睡眠呼吸暂停及低通气指数(AHI) 分为5≤AHI<40组(23例)和AHI≥40组(12例);对照组15例单纯肥胖者.对2组受试者行肺功能、低氧通气反应[HVR,以Δ0.1 s时的口腔内阻断压(P0.1)/Δ脉搏血氧饱和度(SpO2)表示]、高碳酸通气反应[HCVR,以ΔP0.1/Δ呼气末CO2分压(PETCO2)表示]检查及睡眠监测.结果 (1) OSAHS组患者ΔP0.1/ΔSpO2、ΔP0.1/ΔPETCO2与对照组相比差异无显著性(t=1.28、0.57,均P>0.05).OSAHS组ΔP0.1/ΔSpO2与睡眠时最低SpO2呈负相关(r=-0.54,P<0.01),与ΔP0.1/ΔPETCO2呈正相关(r=0.57,P<0.01).(2) 5≤AHI<40组患者的ΔP0.1/ΔSpO2较AHI≥40组增高(t=2.74,P<0.01),ΔP0.1/ΔPETCO2无显著差别.5≤AHI<40组ΔP0.1/ΔSpO2与第1秒钟用力呼气容积/最大呼气流量及AHI呈负相关(r=-0.42,P<0.05;r=-0.68,P<0.01);AHI≥40组ΔP0.1/ΔSpO2与睡眠时最低SpO2呈负相关(r=-0.58,P<0.05),与ΔP0.1/ΔPETCO2呈正相关(r=0.59,P<0.05).结论 OSAHS患者HCVR无明显改变,但HVR随AHI的增加呈先升高后降低的双相变化,且与睡眠时最低SpO2及HCVR密切相关.     

Progesterone therapy for sleep apnea syndrome evaluated by occlusion pressure responses to exogenous loading

We investigated the mechanisms of the beneficial effect derived from progesterone therapy for sleep apnea syndrome (SAS). Nine patients with SAS were treated for 7 days with chlormadinone acetate (CMA), a respiratory stimulant known to increase not only CO2 and hypoxic chemosensitivity but also respiratory drive response for ventilatory loading. They were examined as to sleep events and ventilatory control during wakefulness before and during CMA treatment. Apnea-hypopnea index was significantly reduced from 51.1 +/- 5.7 to 43.6 +/- 8.1 episodes/h (p less than 0.05). The ratio of desaturation time with more than 4% SaO2 fall to total sleep time was diminished in seven of nine patients, and its mean value decreased from 44.9 +/- 8.6 to 28.7 +/- 8.1% (p less than 0.05). Both hypercapnic ventilatory response (HCVR) and load response during wakefulness were significantly increased, although isocapnic hypoxic ventilatory response (HVR) was not significantly enhanced by CMA. The degree of augmentation in awake load response as well as in HCVR was positively correlated with that of improvement in sleep-disordered breathing. Moreover, patients who did not show amelioration in oxygen desaturation were found to be incapable of increasing load response despite increased HCVR. We conclude that CMA therapy for sleep apnea syndrome is effective in the patients whose load response as well as respiratory control activity are augmented during wakefulness.     

Almitrine increases the steady-state hypoxic ventilatory response in hypoxic chronic air-flow obstruction

Almitrine, a peripheral chemoreceptor agonist, exerts beneficial effects on blood gases in patients with hypoxic chronic air-flow obstruction, but as these patients exhibit poor ventilatory responses to hypoxia, the mechanism for this improvement is not clear. The effect of a 100-mg dose of almitrine given orally on ventilation and the steady-state hypoxic ventilatory response (HVR) were measured in a randomized, double-blind, placebo-controlled manner in 7 patients with severe hypoxic chronic air-flow obstruction. The isocapnic HVR (delta VE/delta SaO2) was calculated from the changes in ventilation and SaO2 from breathing 60% O2 to breathing air with the addition of CO2 to maintain isocapnia (as estimated from a transcutaneous CO2 electrode). Resting ventilation while breathing air and isocapnic HVR were measured before and 3 h after almitrine or placebo. Almitrine caused no significant change in resting ventilation. There was, however, a large increase in HVR after almitrine (almitrine: -1.5 L/min/%SaO2; range, -0.5 to -3.1; control: -0.4; range, -0.3 to -1.3), but no change after placebo. Almitrine is a powerful stimulant of chemosensitivity and of the hypoxic ventilatory response in chronic hypoxemia, with potential benefit to patients with chronic air-flow obstruction in respiratory failure.     

Comparison of transcutaneous and alveolar partial pressure of carbon dioxide during carbon dioxide breathing in healthy children

In 18 healthy children three to 13 years of age, the transcutaneous partial pressure of carbon dioxide (PtcCO2) (Radiometer electrode) and the alveolar partial pressure of carbon dioxide (PACO2) (Beckman analyzer) were measured simultaneously during the breathing of room air and 5 percent carbon dioxide. The PtcCO2 electrode was placed on the anterior thorax and heated to 42 degrees C. The PACO2 was calculated on the 4/5 part of the carbon dioxide expired trace. Minute ventilation (VE) was measured in 11 cases. There was a significant correlation between PtcCO2 (in millimeters of mercury) and PACO2 (in millimeters of mercury) while breathing room air (PtcCO2 = 0.82 PACO2 + 19.7; r = 0.55; p less than 0.02) and while breathing 5 percent carbon dioxide (PtcCO2 = 0.77 PACO2 + 22.5; r = 0.61; p less than 0.01); however, the ratio of PtcCO2 over PACO2 was significantly lower while breathing 5 percent carbon dioxide (p less than 0.01) than while breathing room air. When considering the relationship between the increase in VE (delta VE while breathing 5 percent carbon dioxide and the changes in PACO2 (delta PACO2) or in PtcCO2 (delta PtcCO2), a significant correlation was found only between delta VE and delta PACO2, ie, delta VE = 0.41 delta PACO2 + 0.44 (r = 0.63; p less than 0.01). These results suggest that breathing carbon dioxide modified the factors acting on PtcCO2, possibly by changes in the vasomotor tone of cutaneous blood vessels. These modifications appeared to be variable from subject to subject. Therefore, we conclude that PtcCO2 does not appear to be an accurate quantitative index to assess ventilatory response to carbon dioxide.     

Chemoreflex drive and the dynamics of ventilation and gas exchange during exercise at hypoxia

We tested the hypothesis that the promotion of hypoxic ventilatory responsiveness (HVR) and/or hypercapnic ventilatory responsiveness (HCVR) mostly acting on the carotid body with a changing work rate can be attributed to faster hypoxic ventilatory dynamics at the onset of exercise. Eleven subjects performed a cycling exercise with two repetitions of 6 minutes while breathing at FIO(2) = 12%. The tests began with unloaded pedaling, followed by three constant work rates of 40%, 60%, and 80% of the subject's ventilatory threshold at hypoxia. Reference data were obtained at the 80% ventilatory threshold work rate during normoxia. Using three inhaled 100% O(2) breath tests, a comparison of hypoxia and normoxia revealed an augmentation of HVR in hypoxia, which then significantly increased proportionally with the increase in work rate. In contrast, HCVR using three inhaled 10% CO(2) breath tests was unaffected by the difference in work rate at hypoxia but did exceed its level at normoxia. The decrease in the half-time of hypoxic ventilation became significant with an increase in work rates and was significantly lower than at normoxia. Using a multiregression equation, HVR was found to account for 63% of the variance of hypoxic ventilatory dynamics at the onset of exercise and HCVR for 9%. O(2) uptake on-kinetics and off-kinetics under hypoxic conditions were significantly slower than under normoxic conditions, whereas they were not altered by the changing work rates at hypoxia. These results suggest that the faster hypoxic ventilatory dynamics at the onset of exercise can be mostly attributed to the augmentation of HVR with an increase in work rates rather than to HCVR. Otherwise, O(2) uptake dynamics are affected by the lower O(2), not by the changing work rates under hypoxic conditions.