Maintenance of ventilatory control by CO2 in the rat during growth and aging

The long-term adjustment of ventilation and blood gases throughout life was studied in halothane anaesthetized male Wistar rats of various ages (1.5–20 months). Basal metabolic rate (O₂ consumption, CO₂ production), ventilation and ventilatory response to CO₂ changed significantly during growth and aging, whereas arterial partial pressure of CO₂ (P _aCO₂) and pH remained unchanged. Changes in the rate of CO₂ production were associated with proportional changes in alveolar ventilation and in the sensitivity of the ventilatory control system to a CO₂ stimulus at various ages. Ventilatory equivalent (ratio of alveolar ventilation to CO₂ production) and the slope of the CO₂/ventilation response line normalized for CO₂ production were maintained constant throughout life, despite significant changes in the breathing pattern. These findings suggest that P _aCO₂ homeostasis is maintained by ventilatory regulation coupled tightly with CO₂ production throughout life.     

Ventilatory response of the panting dog to hypoxia

Summary The ventilatory response to isocapnic hypoxia was studied in anesthetized dogs during normothermia and thermally induced panting. In the normothermic dog, minute ventilation (_E), tidal volume (V _T) and respiratory frequency (f) did not vary significantly with changes ofPaO₂ above 80–90 mm Hg. Below this value, these three parameters increased substantially with progressively decreasingPaO₂. During panting the ventilatory response was triphasic: 1. withPaO₂ values above 90 mm Hg ventilation remained unaffected; 2. whenPaO₂ progressively decreased from 90 to 45 mm Hg, ventilation increased significantly over the levels of ventilation reached in response to heat alone; 3. withPaO₂ under 45 mm Hg ventilation abruptly decreased as compared to the second phase of the response.V _T increased significantly during the second and third segments as compared to the first. Respiratory frequency progressively decreased whenPaO₂ was under 60 mm Hg Isocapnic hypoxia suppressed thermally induced panting (tachypnea) but led to reduction of evaporative heat loss only at the lowest values ofPaO₂.Apparently, in the panting animal chemical control of respiration is set aside by the thermoregulatory control. However, chemical regulation of respiration may set aside the normal respiratory pattern of thermal polypnea in response to acute chemical stimuli, such as arterial hypoxia.     

Facial cooling and peripheral chemoreflex mechanisms in humans

Aim: Reductions in arterial oxygen partial pressure activate the peripheral chemoreceptors which increase ventilation, and, after cessation of breathing, reduce heart rate. We tested the hypothesis that facial cooling facilitates these peripheral chemoreflex mechanisms. Methods: Chemoreflex control was assessed by the ventilatory response to hypoxia (10% O₂ in N₂) and the bradycardic response to voluntary end‐expiratory apnoeas of maximal duration in 12 young, healthy subjects. We recorded minute ventilation, haemoglobin O₂ saturation, RR interval (the time between two R waves of the QRS complex) and the standard deviation of the RR interval (SDNN), a marker of cardiac vagal activity throughout the study. Measurements were performed with the subject’s face exposed to air flow at 23 and 4 °C. Results: Cold air decreased facial temperature by 11 °C (P < 0.0001) but did not affect minute ventilation during normoxia. However, facial cooling increased the ventilatory response to hypoxia (P < 0.05). The RR interval increased by 31 ± 8% of the mean RR preceding the apnoea during the hypoxic apnoeas in the presence of cold air, compared to 17 ± 5% of the mean RR preceding the apnoea in the absence of facial cooling (P < 0.05). This increase occurred despite identical apnoea durations and reductions in oxygen saturation. Finally, facial cooling increased SDNN during normoxia and hypoxia, as well as during the apnoeas performed in hypoxic conditions (all P < 0.05). Conclusion: The larger ventilatory response to hypoxia suggests that facial cooling facilitates peripheral chemoreflex mechanisms in normal humans. Moreover, simultaneous diving reflex and peripheral chemoreflex activation enhances cardiac vagal activation, and favours further bradycardia upon cessation of breathing.     

Exogenous ghrelin accentuates the acute hypoxic ventilatory response after two weeks of chronic hypoxia in conscious rats

Aim: Ghrelin has been implicated as a modulator of numerous physiological pathways. To date, there have not been any studies describing the role of ghrelin in modulating the chemoreflex control of pulmonary ventilation. Yet the respiratory system impacts, at least to some degree, on virtually all homeostatic control systems. Chronic hypoxia (CH) can cause fundamental changes in ventilatory control, evident by alterations in the acute hypoxia ventilatory response (HVR). As ghrelin plays an important role in metabolic homeostasis, which is tightly linked to ventilatory control, we hypothesized that ghrelin may modulate HVR, especially following CH. Methods: Whole body plethysmography was used to measure the HVR (8% O₂ for 10 min) in male Sprague–Dawley rats (body wt ∼180–220 g) before and after 14 days of CH (CH = 10% O₂). During CH, rats received daily subcutaneous injections of either saline (control; n = 5) or ghrelin (150 μg kg⁻¹ day⁻¹; n = 5). The HVR was measured in another four rats that had received daily injections of ghrelin during normoxia for 7 days. Results: Ghrelin did not significantly alter basal ventilatory drive or acute HVR in normoxic rats. However, the acute HVR was accentuated following CH in ghrelin-treated rats compared with saline-treated rats. Conclusions: These results describe the impact that ghrelin has in altering ventilatory control following CH and, although the mechanisms remain to be fully elucidated, provide guidance for future ghrelin-based studies interpreting physiological data indirectly related to the chemoreflex control of pulmonary ventilation.     

Metabolic consequences of reduced frequency breathing during submaximal exercise at moderate altitude

Summary The intention of this study was to determine the metabolic consequences of reduced frequency breathing (RFB) at total lung capacity (TLC) in competitive cyclists during submaximal exercise at moderate altitude (1520 m; barometric pressure, P _B=84.6 kPa; 635 mm Hg). Nine trained males performed an RFB exercise test (10 breaths · min ^–1) and a normal breathing exercise test at 75–85% of the ventilatory threshold intensity for 6 min on separate days. RFB exercise induced significant (P<0.05) decreases in ventilation (V _E), carbon dioxide production (VCO₂), respiratory exchange ratio. (RER), ventilatory equivalent for O₂ consumption (V _E/VO₂), arterial O₂ saturation and increases in heart rate and venous lactate concentration, while maintaining a similar OZ consumption (VO₂). During recovery from RFB exercise (spontaneous breathing) a significant (P< 0.05) decrease in blood pH was detected along with increases in V _E, VO₂, VCO₂, RER, and venous partial pressure of carbon dioxide. The results indicate that voluntary hypoventilation at TLC, during submaximal cycling exercise at moderate altitude, elicits systemic hypercapnia, arterial hypoxemia, tissue hypoxia and acidosis. These data suggest that RFB exercise at moderate altitude causes an increase in energy production from glycolytic pathways above that which occurs with normal breathing.     

5-HT1A, but not 5-HT2 and 5-HT7, receptors in the nucleus raphe magnus modulate hypoxia-induced hyperpnoea

Aim: In the present study, we assessed the role of 5‐hydroxytryptamine (5‐HT) receptors (5‐HT_1A, 5‐HT₂ and 5‐HT₇) in the nucleus raphe magnus (NRM) on the ventilatory and thermoregulatory responses to hypoxia. Methods: To this end, pulmonary ventilation (V_E) and body temperature (T_b) of male Wistar rats were measured in conscious rats, before and after a 0.1 μL microinjection of WAY‐100635 (5‐HT_1A receptor antagonist, 3 μg 0.1μL^?1, 56 mm ), ketanserin (5‐HT₂ receptor antagonist, 2 μg 0.1μL^?1, 36 mm ) and SB269970 (5‐HT₇ receptor antagonist, 4 μg 0.1 μL^?1, 103 mm ) into the NRM, followed by 60 min of severe hypoxia exposure (7% O₂). Results: Intra‐NMR microinjection of vehicle (control rats) or 5‐HT antagonists did not affect V_E or T_b during normoxic conditions. Exposure of rats to 7% O₂ evoked a typical hypoxia‐induced anapyrexia after vehicle microinjections, which was not affected by microinjection of WAY‐100635, SB269970 or ketanserin. The hypoxia‐induced hyperpnoea was not affected by SB269970 and ketanserin intra‐NMR. However, the treatment with WAY‐100635 intra‐NRM attenuated the hypoxia‐induced hyperpnoea. Conclusion: These data suggest that 5‐HT acting on 5‐HT_1A receptors in the NRM increases the hypoxic ventilatory response.     

Enhanced chemosensitivity after intermittent hypoxic exposure does not affect exercise ventilation at sea level

The purpose of the present study was to test the hypothesis that the ventilatory response to exercise at sea level may increase after intermittent hypoxic exposure for 1 week, accompanied by an increase in hypoxic or hypercapnic ventilatory chemosensitivity. One group of eight subjects (hypoxic group) were decompressed in a chamber to 432 torr (where 1 torr=1.0 mmHg, simulating an altitude of 4,500 m) over a period of 30 min and maintained at that pressure for 1 h daily for 7 days. Oxygen uptake and pulmonary ventilation (V_E) were determined at 40%, 70%, and 100% of maximal oxygen uptake at sea level before (Pre) and after (Post) 1 week of daily exposures to hypoxia. The hypoxic ventilatory response (HVR) was determined using the isocapnic progressive hypoxic method as an index of ventilatory chemosensitivity to hypoxia, and the hypercapnic ventilatory response (HCVRSB) was measured by means of the single-breath carbon dioxide method as an index of peripheral ventilatory chemosensitivity to hypercapnia. The same parameters were measured in another group of six subjects (control group). In the hypoxic group, resting HVR increased significantly (P<0.05) after intermittent hypoxia and HCVRSB increased at Post, but the change was not statistically significant (P=0.07). In contrast, no changes in HVR and HCVRSB were found in the control group. There were no changes in either V_E or the ventilatory equivalent for oxygen during maximal and submaximal exercise at sea level throughout the experimental period in either group. These results suggest that the changes in resting hypoxic and peripheral hypercapnic chemosensitivities following short-term intermittent hypoxia have little effect on exercise ventilation at sea level. Electronic Publication     

Effects of β2-adrenergic stimulation on exercise capacity in normal subjects

β2-Adrenergic receptor agonists are believed to present with ergogenic properties. However, how combined respiratory, cardiovascular and muscular effects of these drugs might affect exercise capacity remain incompletely understood. The effects of salbutamol were investigated in 23 healthy subjects. The study was randomised, placebo-controlled in double-blind and followed a cross-over design. Salbutamol was given at the dose of 10 μg/min in 11 subjects and 20 μg/min iv in the other 12 subjects. Measurements included muscle sympathetic nerve activity (MSNA), ventilatory responses to hyperoxic hypercapnia (7% CO₂ in O_2, central chemoreflex), isocapnic hypoxia (10% O₂ in N₂, peripheral chemoreflex) and isometric muscle contraction followed by a local circulatory arrest (metaboreflex), cardiopulmonary exercise test (CPET) variables and isokinetic muscle strength. Salbutamol 10 μg/min increased heart rate and blood pressure, while MSNA burst frequency remained unchanged. Peripheral chemosensitivity increased, as evidenced by an increased ventilatory response to hypoxia, but ventilatory responses to hypercapnia or muscle ischaemia remained unchanged. The effects of salbutamol 20 μg/min were similar. Both doses of salbutamol did not affect CPET. Only the higher dose of salbutamol decreased the anaerobic threshold, but this was not associated with a change in VO₂ max. Salbutamol increased the slopes of ventilation as a function of VO₂ (P < 0.05) and VCO₂ (P < 0.001) during CPET. Maximal isokinetic muscle strength was not affected by salbutamol. In conclusion, the acute administration of either low or high dose salbutamol does not affect exercise capacity in normal subjects, in spite of an earlier anaerobic threshold and increased chemosensitivity.     

Control of breathing in newborn mice lacking the beta‐2 nAChR subunit

Aim: To study the ventilatory and arousal/defence responses to hypoxia in newborn mutant mice lacking the β2 subunit of the nicotinic acetylcholine receptors. Methods: Breathing variables were measured non‐invasively in mutant (n =31) and wild‐type age‐matched mice (n = 57) at 2 and 8 days of age using flow barometric whole‐body plethysmography. The arousal/defence response to hypoxia was determined using behavioural criteria. Results: On day 2, mutant pups had significantly greater baseline ventilation (16%) than wild‐type pups (P < 0.02). Mutant pups had a decreased hypoxic ventilatory declines. Arousal latency was significantly shorter in mutant than in wild‐type pups (133 ± 40 vs. 146 ± 20 s, respectively, P < 0.026). However, the duration of movement elicited by hypoxia was shorter in mutant than in wild‐type pups (14.7 ± 5.9 vs. 23.0 ± 10.7 s, respectively, P < 0.0005). Most differences disappeared on P8, suggesting a high degree of functional plasticity. Conclusion: The blunted hypoxic ventilatory decline and the shorter arousal latency on day 2 suggested that disruption of the β2 nicotinic acetylcholine receptors impaired inhibitory processes affecting both the ventilatory and the arousal response to hypoxia during postnatal development.     

Changes in ventilatory adaptations associated with long-term intermittent hypoxia across the age spectrum in the rat

Intermittent hypoxia (IH) induces alterations in respiratory control that reflect various types of ventilatory plasticity. In freely behaving rats, acute exposure to IH elicits enhancements in normoxic minute ventilation (VE), termed ventilatory long-term facilitation. Exposure to longer time periods of IH induces unique ventilatory adaptations to intermittent hypoxia (VAIH). We hypothesized that long-term IH-induced ventilatory plasticity may be developmentally regulated and thus, IH exposures at progressively later post-natal ages may elicit differential effects on the magnitude of VAIH. To examine this issue, male Sprague-Dawley rats were exposed to 30 continuous days of IH beginning at post-natal ages 1, 10, 30, 60, 180, 360, and 540 days. Control animals were exposed to normoxic conditions with room air. Normoxic VE was significantly higher in IH-exposed rats (p < 0.01) except for the group in which IH was initiated at post-natal age 540 days (p = NS). The magnitude of VAIH was greatest in rats exposed in the immediate post-natal period and gradually diminished with advancing post-natal age. Enhanced normoxic VE was due to significant contributions from both frequency (p < 0.01) and tidal volume (p < 0.01), and could not be accounted for by changes in metabolic rate. We conclude that the magnitude of IH-induced ventilatory plasticity is age-dependent with progressive declines becoming apparent with advancing post-natal age.     

Ventilation during air breathing and in response to hypercapnia in 5 and 16 month-old <Emphasis Type="Italic">mdx</Emphasis> and C57 mice

Previous studies have shown a blunted ventilatory response to hypercapnia in mdx mice older than 7 months. We test the hypothesis that in the mdx mice ventilatory response changes with age, concomitantly with the increased functional impairment of the respiratory muscles. We thus studied the ventilatory response to CO₂ in 5 and 16 month-old mdx and C57BL10 mice (n = 8 for each group). Respiratory rate (RR), tidal volume (VT), and minute ventilation (VE) were measured, using whole-body plethysmography, during air breathing and in response to hypercapnia (3, 5 and 8% CO₂). The ventilatory protocol was completed by histological analysis of the diaphragm and intercostals muscles. During air breathing, the 16 month-old mdx mice showed higher RR and, during hypercapnia (at 8% CO₂ breathing), significantly lower RR (226 ± 26 vs. 270 ± 21 breaths/min) and VE (1.81 ± 0.35 vs. 3.96 ± 0.59 ml min⁻¹ g⁻¹) (P < 0.001) in comparison to C57BL10 controls. On the other hand, 5 month-old C57BL10 and mdx mice did not present any difference in their ventilatory response to air breathing and to hypercapnia. In conclusion, this study shows similar ventilation during air breathing and in response to hypercapnia in the 5 month-old mdx and control mice, in spite of significant pathological structural changes in the respiratory muscles of the mdx mice. However in the 16 month-old mdx mice we observed altered ventilation under air and blunted ventilation response to hypercapnia compared to age-matched control mice. Ventilatory response to hypercapnia thus changes with age in mdx mice, in line with the increased histological damage of their respiratory muscles. J. Gayraud and S. Matecki contributed equally to this work     

Respiratory responses to combined hypoxia and hypothermia in rats after posterior hypothalamic lesions

Urethane-anaesthetised rats were exposed to hypoxia (7% O₂ in N₂) for 5 min periods while body core temperature (T _bc) was maintained within the normal range (37–38° C) using an abdominal heat exchanger. Animals were exposed to hypoxia and after placement of electrolytic lesions in either the anterior (n=6) or posterior hypothalamus (n=6). Neither lesion altered respiration while rats breathed air at either T _bc. At normal T _bc, rats responded to hypoxia with increased ventilation throughout the exposure period. This response was unchanged by lesions in either location. At reduced T _bc rats responded to hypoxia with an initial increase in ventilation followed by depression to below air-breathing levels. This depressive response was unchanged after anterior hypothalamic lesions but eliminated after posterior hypothalamic lesions. It is concluded that neurons either originating in the posterior hypothalamus, or passing through it, play a role in the interaction between cold and hypoxia which leads to inhibition of respiration.     

Hemodynamic and ventilatory response to different levels of hypoxia and hypercapnia in carotid body-denervated rats

OBJECTIVE:

Chemoreceptors play an important role in the autonomic modulation of circulatory and ventilatory responses to changes in arterial O₂ and/or CO₂. However, studies evaluating hemodynamic responses to hypoxia and hypercapnia in rats have shown inconsistent results. Our aim was to evaluate hemodynamic and respiratory responses to different levels of hypoxia and hypercapnia in conscious intact or carotid body-denervated rats.

METHODS:

Male Wistar rats were submitted to bilateral ligature of carotid body arteries (or sham-operation) and received catheters into the left femoral artery and vein. After two days, each animal was placed into a plethysmographic chamber and, after baseline measurements of respiratory parameters and arterial pressure, each animal was subjected to three levels of hypoxia (15, 10 and 6% O₂) and hypercapnia (10% CO₂).

RESULTS:

The results indicated that 15% O₂ decreased the mean arterial pressure and increased the heart rate (HR) in both intact (n = 8) and carotid body-denervated (n = 7) rats. In contrast, 10% O₂ did not change the mean arterial pressure but still increased the HR in intact rats, and it decreased the mean arterial pressure and increased the heart rate in carotid body-denervated rats. Furthermore, 6% O₂ increased the mean arterial pressure and decreased the HR in intact rats, but it decreased the mean arterial pressure and did not change the HR in carotid body-denervated rats. The 3 levels of hypoxia increased pulmonary ventilation in both groups, with attenuated responses in carotid body-denervated rats. Hypercapnia with 10% CO₂ increased the mean arterial pressure and decreased HR similarly in both groups. Hypercapnia also increased pulmonary ventilation in both groups to the same extent.

CONCLUSION:

This study demonstrates that the hemodynamic and ventilatory responses varied according to the level of hypoxia. Nevertheless, the hemodynamic and ventilatory responses to hypercapnia did not depend on the activation of the peripheral carotid chemoreceptors.     

Ventilatory efficiency and exercise tolerance in 101 healthy volunteers

The ventilatory equivalent for CO₂ defines ventilatory efficiency largely independent of metabolism. An impairment of ventilatory efficiency may be caused by an increase in either anatomical or physiological dead space, the latter being the most important mechanism in the hyperpnoea of heart failure, pulmonary embolism, pulmonary hypertension and the former in restrictive lung disease. However, normal values for ventilatory efficiency have not yet been established. We investigated 101 (56 men) healthy volunteers, aged 16–75 years, measuring ventilation and gas exchange at rest (n?=?64) and on exercise (modified Naughton protocol, n?=?101). Age and sex dependent normal values for ventilatory efficiency at rest defined as the ratio ventilation:carbon dioxide output (V˙ _E:V˙CO₂), exercise ventilatory efficiency during exercise, defined as the slope of the linear relationship between ventilation and carbon dioxide output (V˙ _E vs V˙CO₂ slope), oxygen uptake at the anaerobic threshold and at maximum (V˙O_2AT,V˙O_2max, respectively) and breathing reserve were established. Ventilatory efficiency at rest was largely independent of age, but was smaller in the men than in the women [V˙ _E:V˙CO₂ 50.5 (SD 8.8) vs 57.6 (SD 12.6) P<0.05]. Ventilatory efficiency during exercise declined significantly with age and was smaller in the men than in the women (men: (V˙ _E vs V˙CO₂ slope?= 0.13?×?age?+?19.9; women: V˙ _E vs V˙CO₂ slope?= 0.12?×?age?+?24.4). The V˙O_2AT and V˙O_2max were 23 (SD 5) and 39 (SD 7) ml O₂?·?kg?·?min^?1 in the men and 18 (SD 4) and 32 (SD 7) in the women, respectively, and declined significantly with age. The V˙O_2AT was reached at 58 (SD 9)% V˙O_2max. Breathing reserve at the end of exercise was 41% and was independent of sex and age. It was concluded from this study that ventilatory efficiency as well as peak oxygen uptake are age and sex dependent in adults.     

Comparison of the metabolic and ventilatory response to hypoxia and H2S in unsedated mice and rats

Hypoxia alters the control of breathing and metabolism by increasing ventilation through the arterial chemoreflex, an effect which, in small-sized animals, is offset by a centrally mediated reduction in metabolism and respiration. We tested the hypothesis that hydrogen sulfide (H₂S) is involved in transducing these effects in mammals. The rationale for this hypothesis is twofold. Firstly, inhalation of a 20–80 ppm H₂S reduces metabolism in small mammals and this effect is analogous to that of hypoxia. Secondly, endogenous H₂S appears to mediate some of the cardio-vascular effects of hypoxia in non-mammalian species. We, therefore, compared the ventilatory and metabolic effects of exposure to 60 ppm H₂S and to 10% O₂ in small and large rodents (20 g mice and 700 g rats) wherein the metabolic response to hypoxia has been shown to differ according to body mass. H₂S and hypoxia produced profound depression in metabolic rate in the mice, but not in the large rats. The depression was much faster with H₂S than with hypoxia. The relative hyperventilation produced by hypoxia in the mice was replaced by a depression with H₂S, which paralleled the drop in metabolic rate. In the larger rats, ventilation was stimulated in hypoxia, with no change in metabolism, while H₂S affected neither breathing nor metabolism. When mice were simultaneously exposed to H₂S and hypoxia, the stimulatory effects of hypoxia on breathing were abolished, and a much larger respiratory and metabolic depression was observed than with H₂S alone. H₂S had, therefore, no stimulatory effect on the arterial chemoreflex. The ventilatory depression during hypoxia and H₂S in small mammals appears to be dependent upon the ability to decrease metabolism.     

The cross-sectional relationships among hyperthermia-induced hyperventilation,peak oxygen consumption,and the cutaneous vasodilatory response during exercise

To test the hypothesis that the hyperthermia-induced ventilatory response relates to aerobic power and/or the cutaneous vasodilatory response during exercise, we asked 18 subjects to perform 3 kinds of exercise: an incremental exercise to determine peak oxygen consumption ([V\dot] {\dot{\hbox{V}}} O_2peak), a steady state exercise at 50% of [V\dot] {\dot{\hbox{V}}} O_2peak to determine the ventilatory response to increasing body temperature, and a steady state exercise at 60% of [V\dot] {\dot{\hbox{V}}} O_2peak to determine the cutaneous vasodilatory response to increasing body temperature. The ventilatory and cutaneous vasodilatory responses were evaluated by plotting the increase in minute ventilation or in forearm vascular conductance against the increase in oesophageal temperature. Regression analysis revealed that: (1) there was a negative relationship between the hyperthermic ventilatory response and cutaneous vasodilatory response, (2) there was a negative relationship between the hyperthermic ventilatory response and [V\dot] {\dot{\hbox{V}}} O_2peak, and (3) there was a positive relationship between the cutaneous vasodilatory response and [V\dot] {\dot{\hbox{V}}} O_2peak. These results support our hypothesis and suggest that exercise training suppresses the hyperthermic ventilatory response and improves the thermoregulatory response.     

Ventilatory and occlusion pressure response to CO2 and hypoxia with resistive loads

Steady-state responses to hyperoxic hypercapnia and eucapnic hypoxia were measured both as minute ventilation (V_E) and as inspiratory mouth occlusion pressure (P_0.1) with and without 25 cm H₂O/l/s added resistance (R). Reduction in slope of the ventilatory response to CO₂ with R was highly significant in all 3 subjects whereas the response to hypoxia was barely significantly reduced in 1 subject and not significantly decreased in two. Although P_0.1 was higher with than without R under all conditions, the slope of the P_0.1 response to CO₂ with R was not increased in two subjects and only slightly increased in the third. The slope of the P_0.1 response to hypoxia was significantly greater in all subjects with R. Expiratory reserve volume was increased with R but the change was the same with hypoxia and hypercapnia. We conclude that ventilation is better maintained with resistive loading during hypoxia than during hypercapnia and that this results from a greater force output of inspiratory muscles as reflected by a higher P_0.1. This suggests a greater neural output to these muscles.     

Effect of two durations of short-term intermittent hypoxia on ventilatory chemosensitivity in humans

The purpose of this study was to clarify the influence of duration of intermittent hypoxia per day on ventilatory chemosensitivity. Subjects were assigned to three different groups according to the duration of exposure to intermittent hypoxia (12.3 ± 0.2% O₂): a first group (H-1, n = 6) was exposed to hypoxia for 1 h per day, the second group (H-2, n = 6) was exposed for 3 h per day, and the third (C, n = 7) was used as control. Hypoxic and hypercapnic ventilatory responses (HVR and HCVR) were determined before and after 1 week of intermittent hypoxia. HVR was increased significantly (P < 0.05) after intermittent hypoxia in both the H-1 and H-2 groups. However, there was no significant difference in magnitude of increased HVR between H-1 and H-2 groups. HCVR did not show any changes in all groups after intermittent hypoxia. These results suggest that 1 h of daily exposure is as equally effective as 3 h of daily exposure to severe hypoxia for a short period for enhancing ventilatory chemosensitivity to hypoxia.     

Ventilatory threshold during treadmill exercise in kindergarten children

Summary The cardiorespiratory response to graded treadmill exercise was studied in a group of kindergarten children, aged 5 to 6 years. From the non-linear change of pulmonary ventilation with increasing exercise intensity a ventilatory threshold was determined which averaged 28.1±4.9 (SD) ml O₂·min^–1·kg^–1. A significant correlation was established between this ventilatory threshold (ml O₂·min^–1) and the physical working capacity at a heart rate of 170 beats per min (PWC₁₇₀, ml O₂·min^–1):r=0.93,p<0.001. These data show that a ventilatory threshold can be obtained in young children which is an objective index of cardiorespiratory performance capacity.     

Intermittent hypoxia and plasticity of respiratory chemoreflexes in metamorphic bullfrog tadpoles

We tested the hypothesis that intermittent hypoxia elicits plasticity in respiratory chemoreflexes in bullfrog tadpoles. Metamorphic tadpoles (Taylor-Kollros stages XVI-XX) were subjected to intermittent hypoxia (PW(O(2))=45 Torr; 12 h/day) or constant normoxia (PW(O(2))=156 Torr) for 2 weeks before ventilatory responses to hypoxia and hypercarbia were measured. Buccal pressure changes were used to quantify the frequency and amplitude of movements associated with gill and lung ventilation. Morphometric assessment showed that intermittent hypoxia delayed development in comparison with controls. Oxygen consumption was enhanced in tadpoles subjected to intermittent hypoxia; however, this increase was not sufficient to affect basal ventilatory activity or the hypoxic ventilatory response. During acute hypercarbic exposure, tadpoles subjected to intermittent hypoxia showed (1) a greater decrease in gill ventilation frequency and (2) a greater increase in lung ventilation frequency than tadpoles maintained under control conditions. We conclude that intermittent hypoxia augments the responsiveness to hypercarbia, thereby promoting lung ventilation when animals face this stimulus. This manifestation of respiratory plasticity may reflect uncoupling between physiological and morphological development in the bi-modally breathing bullfrog tadpole.