Ventilatory response to CO2 after brief stimulations of the peripheral chemoreceptors in man

Whether or not stimulation of the peripheral chemoreceptors by hypercapnic-hypoxic exposure results in a long-lasting increase in ventilatory activities was studied using the steady state CO2 response test on 12 human subjects. The degree of hypercapnic hypoxia was end-tidal PCO2 (PETCO2) 42.1 +/- 3.0 and PO2 (PETO2) 39.8 +/- 4.7 mmHg, lasting for 5 min. Minute ventilation values at PETCO2 45 mmHg (V45) and PETCO2 at minute volume 15 liter . min-1 (P15) were calculated from the respective CO2 response curves. The differences in V45 and P15 between the control and the 30 min test group were found to be significant (p less than 0.05). These results suggested the left- and upward-shift of the CO2 response curve of the 30 min test group. On the other hand, in 5 of the 12 subjects, three successive CO2 response tests conducted at 0, 30, and 90 min without hypercapnic-hypoxic exposure showed fairly reproducible results, and no statistically significant differences were found between any of the above trials with the parameters S, B, V45, and P15. These results indicated that the CO2 response curve obtained by using the steady state method can be effected for at least 30 min even if the stimulation of the peripheral chemoreceptors is only for brief periods.     

The effects of raising alveolar PCO2 and ventilation separately and together on the sensitivity and setting of the baroreceptor cardiodepressor reflex in man

1. The effects of changes in ventilation and/or alveolar P(CO2) on the baroreflex control of heart rate have been studied in seven experiments on six young men and women who had been trained to control tidal volume and respiratory frequency at various levels independent of alveolar P(CO2), during hyperoxia.2. Intravenous phenylephrine provoked transient rises of directly measured arterial pressure during which individual systolic pressures (P) were linearly related to the following pulse interval (I). Baroreflex sensitivity was expressed as the slope of the regression of I on P, and reflex setting (I(ref)) as I at a single reference arterial pressure (= mean P for the experiment).3. Voluntary control of breathing had little effect on heart rate and arterial pressure (baroreflex setting), but diminished reflex sensitivity.4. Hypercapnia regularly caused tachycardia at the reference pressure (i.e. baroreflex setting lowered). The response was completely or partly reproduced by change of P(A, CO2) at constant ventilation in four subjects but not in two others; in them change of ventilation at constant P(A, CO2) completely mimicked the effect of free-breathing hypercapnia.5. Values of baroreflex sensitivity were relatively scattered. Hypercapnia caused a fall in baroreflex sensitivity in three subjects whether ventilation was fixed or free to rise. After separating the effect of voluntarily controlling ventilation, ventilation per se was without effect on reflex sensitivity.6. It is concluded that hypercapnia and hyperpnoea have separate effects on the baroreflex, the relative magnitudes of which differ from one subject to another. Baroreflex setting and sensitivity vary independently in response to change of ventilation and of P(A, CO2).     

Carotid body chemoreceptor activity in the new-born lamb

1. Tidal volume, carotid artery oxygen tension (P(a,O2)) and blood pressure and chemoreceptor activity in the sinus nerve have been continuously measured and recorded in nine lambs anaesthetized with pentobarbitone sodium, and varying in age from some minutes after birth to 5 days after birth.2. Inhalation of 100% oxygen caused, after a delay of 3-4 sec, a rise in P(a,O2), a fall in minute ventilation (V) and chemoreceptor activity. The respiratory response was abolished after section of both sinus nerves.3. Inhalation of 10% oxygen in nitrogen caused a fall in carotid P(a,O2), a rise in respiration and in chemoreceptor activity. The respiratory response was abolished after both sinus nerves had been cut.4. Minute ventilation, carotid P(a,O2) and chemoreceptor activity increased on breathing 5% CO(2) in air. Section of both sinus nerves did not affect the maximum increase in ventilation but the lag of the respiratory response approximately doubled while respiration increased more slowly.5. From these results, it was calculated that the chemoreceptors had a latency of 0.25-0.5 sec and the time constant of the rate of change of chemoreceptor activity was 10-15 sec.6. The chemoreceptors responded to changes in P(a,O2) of +/-5-10 mm Hg.7. Comparison of these results with those reported in adult animals suggest that the peripheral chemoreceptors are fully mature at birth, that their response does not differ with the age of the lamb and that the carotid body chemoreceptors are concerned both in the mediation of the hypoxic drive to ventilation and in the respiratory response to inhaled CO(2).     

Chemoreceptor reflexes in the new-born infant: effects of varying degrees of hypoxia on heart rate and ventilation in a warm environment

1. We studied the effects of varying degrees of hypoxia for 3 min periods on the heart rate and respiration of thirty-three healthy full-term infants in a warm environment.2. During the first 5 days of life a decrease in alveolar oxygen tension (P(A, CO2)) below 80 mm Hg induced hyperventilation, a decreased alveolar carbon dioxide tension (P(A, CO2)), and tachycardia during the first minute of hypoxia. During the second and third minute, while the decreased P(A, CO2) and tachycardia persisted, ventilation fell. There was a further fall in ventilation when the baby breathed 21% O(2) again. This response was also observed when the inspired gas was heated to 35 degrees C.3. During the first 5 days of life a decrease in P(A, CO2) between 81 and 100 mm Hg did not affect ventilation or P(A, CO2) during the first minute of hypoxia, but still induced a tachycardia and a fall in minute volume during the second and third minute.4. When the P(A, CO2) was elevated and maintained constant during hypoxia, ventilation increased during the first minute and fell during the second and third minutes, suggesting that hypocapnia did not explain the transient ventilatory response to hypoxia.5. After the first week of life a greater and maintained increase in ventilation was seen during hypoxia. This response was potentiated by the addition of CO(2).6. The possibility that changes in the pulmonary circulation, associated with a functionally patent ductus arteriosus, may explain these differences, is discussed.     

The Contribution of Chemoreflex Drives to Resting Breathing in Man

The contribution of automatic drives to breathing at rest, relative to behavioural drives such as "wakefulness", has been a subject of debate. We measured the combined central and peripheral chemoreflex contribution to resting ventilation using a modified rebreathing method that included a prior hyperventilation and addition of oxygen to maintain isoxia at a P(ET,O2) (end-tidal partial pressure of oxygen) of 100 mmHg. During rebreathing, ventilation was unrelated to P(ET,CO2) (end-tidal partial pressure of carbon dioxide) in the hypocapnic range, but after a threshold P(ET,CO2) was exceeded, ventilation increased linearly with P(ET,CO2). We considered the sub-threshold ventilation to be an estimate of the behavioural drives to breathe (mean +/- S.E.M. = 3.1 +/- 0.5 l min(-1)), and compared it to ventilation at rest (mean +/- S.E.M. = 9.1 +/- 0.7 l min(-1)). The difference was significant (Student's paired t test, P < 0.001). We also considered the threshold P(CO2) observed during rebreathing to be an estimate of the chemoreflex threshold at rest (mean +/- S.E.M. = 42.0 +/- 0.5 mmHg). However, P(ET,CO2) during rebreathing estimates mixed venous or tissue P(CO2), whereas the resting P(ET,CO2) during resting breathing estimates P(a,CO2) (arterial partial pressure of carbon dioxide). The chemoreflex threshold measured during rebreathing was therefore reduced by the difference in P(ET,CO2) at rest and at the start of rebreathing (the plateau estimates the mixed venous P(CO2) at rest) in order to make comparisons. The corrected chemoreflex thresholds (mean +/- S.E.M. = 26.0 +/- 0.9 mmHg) were significantly less (paired Student's t test, P < 0.001) than the resting P(ET,CO2) values (mean +/- S.E.M. = 34.3 +/- 0.5 mmHg). We conclude that both the behavioural and chemoreflex drives contribute to resting ventilation. Experimental Physiology (2001) 86.1, 109-116.     

The cardiorespiratory activation response at an arousal from sleep is independent of the level of CO(2)

Arousal from sleep is associated with transient cardiorespiratory activation. Traditionally, this response has been understood to be a consequence of state-dependent changes in the homeostatic control of ventilation. The hypothesis predicts that the magnitude of ventilatory and cardiac responses at an arousal will be a function of the intensity of concurrent respiratory stimuli (primarily PCO(2)). Alternatively, it has been proposed that increased cardiorespiratory activity is due to reflex activation. This hypothesis predicts that the magnitude of the cardiorespiratory response will be independent of respiratory stimuli. To compare these hypotheses we measured minute ventilation (V(i)), heart rate (HR) and blood pressure (BP) during wakefulness and stage 2 sleep, while manipulating P(et)CO(2). Further, we assessed the magnitude of the response of these variables to an arousal from sleep at the various levels of P(et)CO(2). The subjects were male aged 18-25 years. P(et)CO(2) was manipulated by clamping it at four levels during wakefulness [wake eucapnic, sleep eucapnic (Low), and sleep eucapnic +3 mmHg (Medium) and +6 mmHg (High)] and three levels during sleep (Low, Medium and High). The average number of determinations for each subject at each level was 14 during wakefulness and 25 during sleep. Arousals were required to meet American Sleep Disorders Association criteria and were without body movement. The results indicated that average increases in V(i), HR and BP at arousal from sleep did not significantly differ as a function of the level of P(et)CO(2) present at the time of the arousal (all P > 0.05). Further, the magnitude of the ventilatory response to an arousal was significantly less than the values predicted by the homeostatic hypothesis (P < 0.05). We conclude that, in normal subjects, the cardiorespiratory response to an arousal from sleep is not because of a homeostatic response, but of a reflex activation.     

Ventilation-perfusion inequality and carbon dioxide sensitivity in hypoxaemic chronic obstructive pulmonary disease (COPD) and effects of 6 months of long-term oxygen treatment (LTOT).

The aim of our study was to find out how blood gas disturbances in stable, eucapnic, severe chronic obstructive pulmonary disease (COPD) patients with an arterial oxygen tension (PaO(2)) value of 7.7 (6.1-8.4) kPa are affected by ventilation-perfusion (V(A)/Q) relationships and carbon dioxide (CO(2)) sensitivity and how these parameters are influenced by 6 months of long-term oxygen treatment (LTOT). V(A)/Q ratios were measured using the multiple inert gas elimination technique (MIGET). Mouth occlusion pressure 0.1 s after onset of inspiration (Pi0.1) and minute ventilation (V(E)) were measured to assess respiratory drive response (DeltaPi0.1/DeltaPCO(2)) and hypercapnic ventilatory response (HCVR) to CO(2) rebreathing. At the start of LTOT, a normal median respiratory drive response level of 1.2 (0.2-2.3) cm H2O/kPa and a low median HCVR as compared with healthy individuals (P<0.001) were found. However, 7.9 (0-29.8)% of the VE, was directed towards hypoperfused lung areas. The dispersion of ventilation (log SDV; 0.47-1.76), and the dispersion of perfusion (log SDQ; 0.66-1.07) were wider than normal. The PaO(2) level correlated inversely with mean V(A)/Q ratio for ventilation (V mean) and shunt. The PaCO(2) level correlated inversely with HCVR and vital capacity. After 6 months of LTOT, no significant changes in daytime blood gas levels, CO(2)-sensitivity or VA/Q ratios were found. VE tended to be reduced by 1.0 l min-1. Conclusions: An elevated V mean and probably shunting are important contributing factors for the reduced PaO(2) and hypercapnic ventilatory response is a major determinant of PaCO(2) in eucapnic stable hypoxaemic COPD. Six months of LTOT does not affect blood gases, CO(2) sensitivity or ventilation-perfusion relationships.     

Muscle afferent activation causes ventilatory and cardiovascular responses during concurrent hypercapnia in humans

Respiratory and cardiovascular responses to muscle mechanoreflex (passive calf stretch) and metaboreflex activation (local circulatory occlusion) were examined during inhalation of a hypercapnic gas mixture in four trials. These controlled for the effects of central command, metabolite sensitization of muscle afferents and hypercapnia-induced elevation of central respiratory drive. In an isokinetic dynamometer, with circulation through the right leg occluded by inflation of a thigh cuff, 13 participants either rested (control trial; CON) or plantarflexed their ankle at 50% maximal force for 1.5 min (voluntary exercise trial; EX). Thereafter, circulatory occlusion was maintained and the calf passively stretched before return to the resting position. Both trials were performed while breathing air, as well as while breathing a normoxic, hypercapnic (5% CO(2)) gas mixture (CO(2) trial and CO(2)+EX trial). Hypercapnic gas inhalation increased baseline minute ventilation (V), heart rate and mean arterial pressure (+27.67 ± 1.74 l min(-1), +7 ± 0.85 beats min(-1) and +13 ± 3.41 mmHg, respectively; means ± SEM) above control values (9.78 ± 0.86 l min(-1), 62 ± 2.3 beats min(-1) and 88 ± 2.6 mmHg, respectively). Voluntary exercise further increased these variables from baseline during both trials (P < 0.05). During the continued circulatory occlusion after voluntary exercise, mean arterial pressure remained significantly elevated (P < 0.05). Minute ventilation returned to baseline during circulatory occlusion following exercise in the EX trial, but in the CO(2)+EX trial the V remained elevated at end-exercise levels during this period (+7.12 ± 1.13 l min(-1)). Passive stretch caused further increases in V during CO(2)+EX and CO(2) trials but not in CON and EX. These results indicate that in the absence of central command, either muscle metaboreflex and/or mechanoreflex activation stimulates ventilation during concurrent hypercapnia.     

Respiratory and circulatory effects of breathing 100% oxygen in the new-born lamb before and after denervation of the carotid chemoreceptors

1. Methods are described for measuring tidal volume and frequency, end-tidal CO(2), blood pressure and heart rate, and arterial gas tensions in the unanaesthetized new-born lamb.2. The resting values of minute ventilation (V)/kg body wt. and arterial oxygen and carbon dioxide tension, (P(a, o2)) and (P(a, CO2)) were similar to those which have been reported in the new-born baby. There was a direct and significant relation between P(a, o2) and P(a, CO2) and the age of the lamb.3. Thirty-five unanaesthetized lambs aged 40 min to 10 days breathed 100% oxygen; minute ventilation fell by an average of 19% of control, end-tidal CO(2) increased and the ratio of change in tidal volume (DeltaV(T)) to change in pressure (DeltaP) (DeltaV(T)/DeltaP) remained constant. In a proportion of lambs, a small decrease in blood pressure and heart rate was observed. The effect of breathing 100% O(2) on lung compliance was variable.4. These changes in ventilation were virtually abolished after both sinus nerves had been cut.5. The results therefore suggest that a significant hypoxic drive to ventilation exists in the new-born lamb and that this drive is mediated by functioning and mature peripheral chemoreceptors.6. Preliminary evidence suggested that, on 100% O(2), the sensitivity of new-born lambs to inhaled CO(2) was reduced.     

Impaired ventilation and metabolism response to hypoxia in histamine H1 receptor-knockout mice

The role of central histamine in the hypoxic ventilatory response was examined in conscious wild-type (WT) and histamine type1 receptor-knockout (H1RKO) mice. Hypoxic gas (7% O(2) and 3% CO(2) in N(2)) exposure initially increased and then decreased ventilation, referred to as hypoxic ventilatory decline (HVD). The initial increase in ventilation did not differ between genotypes. However, H1RKO mice showed a blunted HVD, in which mean inspiratory flow was greater than that in WT mice. O(2) consumption (V(O2)) and CO(2) excretion were reduced 10min after hypoxic gas exposure in both genotypes, but (V(O2)) was greater in H1RKO mice than in WT mice. The ratio of minute ventilation to (V(O2)) during HVD did not differ between genotypes, indicating that ventilation is adequately controlled according to metabolic demand in both mice. Peripheral chemoreceptor sensitivity did not differ between genotypes. We conclude that central histamine contributes via the H1 receptor to changes in metabolic rate during hypoxia to increase HVD in conscious mice.     

Arterial P CO2 and lung ventilation in man exposed to 1-5% CO2 in the inspired gas

Conflicting results have been published on the shape of the curve relating the change in lung ventilation to the change in alveolar or arterial PCO2 induced by increased inspired CO2 (the CO2 sensitivity). In this study eight human subjects with in-dwelling arterial cannulae were each exposed to five different levels of increased inspired CO2 (1-5%). Arterial PCO2 and ventilation were measured in the 7th minute of each period of CO2 exposure. Each CO2 exposure period was flanked by control periods in which similar measurements were carried out during air breathing. We found non-linear increases in both ventilation and arterial PCO2 with increasing levels of inspired CO2. When 5% CO2 in air was inspired the arterial PCO2 increased by about 15% of the inspired CO2 load. There was no significant non-linearity in the relation between change in alveolar ventilation (normalized to body surface) and change in arterial PCO2. The inter-individual variation in CO2 sensitivity was less when alveolar ventilation was normalized to the CO2 output rather than to body surface area. We conclude that the sensitivity to CO2 is close to constant within the range 0-5% CO2 in the inspired gas.     

Changes in chemoreflex characteristics following acute carbonic anhydrase inhibition in humans at rest

The effect of carbonic anhydrase (CA) inhibition with acetazolamide (ACZ, 10 mg kg(-1) I.V.) on the peripheral and central chemosensitivity and breathing pattern was investigated in four women and three men aged 25 +/- 3 years using a modified version of Read's rebreathing technique. Subjects were exposed to dynamic increases in CO2 in hypoxic and hyperoxic backgrounds during control conditions and following acute CA inhibition. All manoeuvres were repeated twice and averaged for data analysis. The central chemoreflex sensitivities, estimated from the slopes of the ventilatory response to CO2 during hyperoxic rebreathing, increased following acute CA inhibition (control vs. ACZ treatment: 1.87 +/- 0.66 vs. 4.07 +/- 1.03 l x min(-1) (mmHg CO2)(-1), P < 0.05). The increased slope was reflected by an increase in the rate of rise of tidal volume and breathing frequency. Furthermore with ACZ, there was a left-ward shift of the ventilation vs. end-tidal PCO2 curve during hyperoxic hypercapnia but not hypoxic hypercapnia. The peripheral chemoreflex sensitivity was isolated by subtracting the hyperoxic slope (central only) from the hypoxic slope (central and peripheral). Following ACZ administration, the peripheral chemosensitivity was blunted (control vs. ACZ treatment: 3.66 +/- 0.92 vs. 1.33 +/- 0.46 l x min(-1) (mmHg CO2)(-1), P < 0.05). In conclusion, acute CA inhibition enhanced the central chemosensitivity to CO2 but diminished the peripheral chemosensitivity.     

The long-term effect of nedocromil sodium on the maximal degree of airway narrowing to methacholine in atopic asthmatic subjects

Airway hyperresponsiveness in asthma is characterized by increased airway sensitivity and by excessive maximal airway narrowing. Long-term inhalation therapy with nedocromil sodium has been shown to reduce increased airway sensitivity in asthma. However, it is unknown whether it also attenuates excessive airway narrowing. We studied the long-term effects of nedocromil on the maximal degree of airway narrowing to methacholine. Twenty-seven atopic asthmatic adults (21-39 years), with a measurable maximal-response plateau on the dose-response curve (20-55% fall in FEV1), were randomly allocated into two parallel treatment groups. They received either inhaled nedocromil 4 mg q.i.d. or placebo, for 8 weeks following a 2 week baseline period. Every 2 weeks, complete dose-response curves to inhaled methacholine were obtained. The response was measured by FEV1 and by volume history standardized partial expiratory flow-volume curves (V40p). A maximal-response plateau was considered if three or more of the highest data points fell within a 5% response range, the maximal response being the average value on the plateau (MFEV1, MV40p). Airway sensitivity was defined as the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20FEV1) or 40% fall in V40p (PC40 V40p). Twenty-four subjects completed the study. Baseline FEV1 or V40p did not change during either treatment (P greater than 0.07). There were no significant changes in MFEV1 or MV40p during treatment with nedocromil (P greater than 0.07). Neither were these changes significantly different between the two groups (P greater than 0.25).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of hypoxia in the new-born lamb before and after denervation of the carotid chemoreceptors

1. Twenty-seven unanaesthetized new-born lambs, 6 hr-10 days old, responded to two levels of inspired oxygen, 125 and 110 mm Hg (alveolar CO(2) being controlled) with a sustained increase in minute ventilation (V), a small increase in heart rate and a less consistent rise in systemic blood pressure.2. An increase in V was observed when arterial oxygen tension (P(a), (O2)) had fallen by 6-15 mm Hg. There appeared to be no fixed threshold of P(a), (O2) at which ventilation started to increase.3. The increase in ventilation caused by these levels of hypoxia was significantly and directly related to the age of the lamb and to its control alveolar CO(2).4. More severe hypoxia caused a progressive increase in V until P(a), (O2) was about 25 mm Hg when respiration failed. This increase at P(a), (O2) > 25 mm Hg was markedly potentiated when alveolar P(CO2) (P(A), (CO2)) was increased and abolished after bilateral denervation of the carotid chemoreceptors.5. Significant (> 10%) left-to-right shunts were found in ten out of twelve lambs lightly anaesthetized with pentobarbitone sodium, breathing air. Hypoxia diminished the left-to-right pressure gradient largely by its pressor effect on the pulmonary circulation. When inspired O(2) tension (P(I), (O2)) was 70 mm Hg, all seven lambs studied showed a reversal of the pressure gradient and evidence of right-to-left shunts (11-42%) across the ductus arteriosus.6. The implications of these findings have been discussed with reference to previous studies of the new-born response to hypoxia and it is concluded that the peripheral chemoreceptors are fully active at birth and in the new-born period.     

Low-dose acetazolamide reduces the hypoxic ventilatory response in the anesthetized cat

Low intravenous dose acetazolamide causes a decrease in steady-state CO(2) sensitivity of both the peripheral and central chemoreflex loops. The effect, however, on the steady-state hypoxic response is unknown. In the present study, we measured the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the isocapnic steady-state hypoxic response in anesthetized cats. Before and after acetazolamide administration, the eucapnic steady-state hypoxic response in these animals was measured by varying inspiratory P(O2) levels to achieve steady-state Pa(O2) levels between hyperoxia Pa(O2) approximately 55 kPa, approximately 412 mmHg) and hypoxia (Pa(O2) approximately 7 kPa, approximately 53 mmHg). The hypoxic ventilatory response was described by the exponential function V(I) = G exp (-DP(o2) + A with an overall hypoxic sensitivity G, a shape parameter D and ventilation during hyperoxia A. Acetazolamide significantly reduced G from 3.057 +/- 1.616 to 1.573 +/- 0.8361 min(-1) (mean +/- S D). Parameter A increased from 0.903 +/- 0.257 to 1.193 +/- 0.321 min(-1), while D remained unchanged. The decrease in overall hypoxic sensitivity by acetazolamide is probably mediated by an inhibitory effect on the carotid bodies and may have clinical significance in the treatment of sleep apneas, particularly those cases that are associated with an increased ventilatory sensitivity to oxygen and/or carbon dioxide.     

Conditions governing the pulmonary vascular response to ventilation hypoxia and hypoxaemia in the dog

1. Isolated lung lobes of the dog perfused through the pulmonary circulation only with atropinized autologous blood obtained by bleeding out the animal under general anaesthesia or following premedication with morphine hydrochloride were subjected to repetitive tests of ventilation hypoxia, the control and test gas mixtures containing similar concentrations of CO(2).2. The pulmonary vasomotor response to ventilation hypoxia depended upon the temperature of the perfusate and the time which had elapsed from the death of the animal to the start of perfusion, termed the ;ischaemic period'. The higher blood temperatures and shorter ischaemic periods favoured a pulmonary vasopressor response to hypoxia, and the lower temperatures and longer ischaemic periods a vasodepressor response or an absence of response.3. The vasopressor responses to hypoxia were associated with a rise in the pH (average, 0.09 in 5 experiments) and a fall in the P(CO2) of the blood. There were no consistent changes in the pH and P(CO2) of the blood accompanying vasodepressor responses.4. The vasopressor responses could be obtained over periods of perfusion lasting 4 hr or longer.5. It is suggested that changes in the composition of blood equilibrated in the isolated perfused lung cannot be predicted from in vitro dissociation curves.     

Interaction between resting pulmonary ventilation function and cardiac autonomic function assessed by heart rate variability in young adults

An association between ambient air pollution and reduced cardiac autonomic function assessed by heart rate variability (HRV) mainly in elderly persons has been suggested by a number of epidemiological studies, but the link between the HRV and pulmonary function in humans remains unknown although such air pollution should primarily affect pulmonary function. To clarify this link, pulmonary ventilation parameters such as oxygen uptake (V(O(2))) and carbon dioxide output (V(CO(2))), as well as the HRV with spectral analysis (high- and low-frequency components of HRV, i.e., CCV(HF) and CCV(LF), reflecting cardiac parasympathetic and sympathetic activities, respectively), were measured in 66 healthy women aged 19-20 years after an overnight fast of 12 h. Significant correlations were found between the CCV(HF) of HRV and both the end-tidal carbon dioxide concentration (FET(CO(2))) and gas exchange ratio (V(CO(2))/V(O(2))) in the subjects (partial correlation coefficients r = 0.354 and 0.320, respectively), whereas there was no significant connection between the FET(CO(2)) and the V(CO(2))/V(O(2)). Similarly, the CCV(LF) correlated significantly with the resting tidal volume of lung (r = 0.364). These findings suggest that resting pulmonary ventilation function interacts with cardiac autonomic function assessed by the HRV, at least in healthy young adults, which may be useful for explaining the pathophysiology concerning the short-term effect of air pollution such as fine particulate matter on cardiovascular function.     

The respiratory effects in man of altering the time profile of alveolar carbon dioxide and oxygen within each respiratory cycle

1. Breathing hypoxic gas through an external dead space (ca. 1200 c.c.) stimulated ventilation disproportionately. A loop (ca. 250 c.c.) in the inspiratory pathway reduced the effect.2. The alveolar time patterns of P(CO) (2) and P(O) (2) characteristic of tube breathing with or without the loop have been simulated in moderate hypoxia by changing the composition of inspired gas at selected intervals after the beginning of inspiration.3. Supplying CO(2)-free gas in late inspiration usually stimulated ventilation, but less than did real tube breathing. Supplying CO(2)-free gas early in inspiration usually depressed ventilation. The difference between the ;CO(2)-free late' and ;CO(2)-free early' effects was 20% of the control ventilation (P < 0.001), i.e. was nearly the same as between the effects of real tube breathing without and with the loop.4. Tube-like P(A, O) (2) time patterns had no effects.5. A-a P(CO) (2) and P(O) (2) gradients remained constant throughout.6. The V(E), f and V(T) relations were unaltered in tube breathing.7. The respiratory system can discriminate between small differences in time patterns of P(A, CO) (2) but not of P(A, O) (2); the signal is amplified by steady hypoxia. The arterial chemoreceptors are probably responsible for these effects.     

Arterial chemoreceptors, ventilation and heart rate in man.

1. Transient changes of heart rate (HR) and ventilation were recorded following step changes in alveolar gas composition in three healthy subjects. From a steady state of normo- or slightly hypercapnic hypoxia (PA,CO2 38-46 torr, PA,O2 50-60 torr) arterial chemoreceptor stimulation was transiently relieved by breathing a CO2-free mixture for two breaths, either pur O2 (causing a fall in PA,CO2 and a rise in PA,O2; O2 test) or a low O2 mixture (causing a fall in PA,CO2 without any change in PA, O2; CO2 test). For both test types ventilation was either allowed to change freely ('free-breathing' tests) or was consciously maintained at the pre-test level by the subjects ('controlled-breathing tests). The circulatory delay from the lungs to the ear was measured with a sensitive ear oximeter. 2. In all 'free-breathing' tests ventilation decreased significantly after a mean latency of 5.2 sec; the average lung-ear circulation time was 4.9 sec. HR increased slightly above pre-test levels in eighty-one of one hundred and four tests of all types, the changes being significant after a latency identical to that of the ventilatory changes. Except in the 'controlled-breathing' CO2 tests this early tachycardia was followed by a decrease in HR within the following 5-6 sec. 3.These findings indicate that the primary effect of withdrawal of arterial chemoreceptor stimulation in conscious man as in the anesthetized animal is tachycardia. The secondary development of bradycardia in 'free-breathing' CO2 tests is probably due to the operation of a lung reflex sensing changes in ventilation. The absence of bradycardia in 'controlled-breathing' CO2 tests and its presence in 'controlled-breathing' O2 tests, finally, suggest that relief of systemic hypoxia causes a slowing of the heart not due to lung reflexes but to some other mechanism which operates with a latency nearly twice as long as the arterial chemoreflex.