Lack of positive interaction between CO2 and hypoxic stimulation for PCO2–VAS response slope in humans

Masuda, Atsuko; Ohyabu, Yoshio; Kobayashi, Toshio; Yoshino, Chikako; Sakakibara, Yoshikazu; Komatsu, Teisuke; Honda, Yoshiyuki

doi:10.1016/s0034-5687(01)00228-6

Cited by 20 publications

(14 citation statements)

References 37 publications

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“…CO 2 -potentiation phenotypes and chromosome 5. Masuda et al (20) recently demonstrated potentiated CO 2 gain in humans, which ranged between end-tidal PCO 2 of 45 to Ͼ60 Torr. The CO 2 potentiation was observed at extreme inspirates of hypercapnia (FI CO 2 ϭ 0.07) with hyperoxic or hypoxic admixtures (FI O 2 ϭ 0.93 or 0.11, respectively).…”

Section: Discussionmentioning

confidence: 98%

“…THE INTERACTIVE MECHANISMS that regulate breathing during coexposure to hypercapnic and hypoxic inspirates are complex and may involve multiple chemoreceptive pathways. It is generally accepted, however, that human subjects (20) and other larger mammalian species (8,10) show an increased slope of the hypercapnic ventilatory sensitivity (HCVS) curve when the O 2 tension is simultaneously lowered. In one study, Kobayashi et al (17) suggested that genetic factors were important in determining variation in HCVS responses when measured with admixtures of hypoxia.…”

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confidence: 99%

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Interactions in hypoxic and hypercapnic breathing are genetically linked to mouse chromosomes 1 and 5

Tankersley¹,

Broman

2004

Journal of Applied Physiology

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The genetic basis for differences in the regulation of breathing is certainly multigenic. The present paper builds on a well-established genetic model of differences in breathing using inbred mouse strains. We tested the interactive effects of hypoxia and hypercapnia in two strains of mice known for variation in hypercapnic ventilatory sensitivity (HCVS); i.e., high gain in C57BL/6J (B6) and low gain in C3H/HeJ (C3) mice. Strain differences in the magnitude and pattern of breathing were measured during normoxia [inspired O(2) fraction (Fi(O(2))) = 0.21] and hypoxia (Fi(O(2)) = 0.10) with mild or severe hypercapnia (inspired CO(2) fraction = 0.03 or 0.08) using whole body plethysmography. At each level of Fi(O(2)), the change in minute ventilation (Ve) from 3 to 8% CO(2) was computed, and the strain differences between B6 and C3 mice in HCVS were maintained. Inheritance patterns showed potentiation effects of hypoxia on HCVS (i.e., CO(2) potentiation) unique to the B6C3F1/J offspring of B6 and C3 progenitors; i.e., the change in Ve from 3 to 8% CO(2) was significantly greater (P < 0.01) with hypoxia relative to normoxia in F1 mice. Linkage analysis using intercross progeny (F2; n = 52) of B6 and C3 progenitors revealed two significant quantitative trait loci associated with variable HCVS phenotypes. After normalization for body weight, variation in Ve responses during 8% CO(2) in hypoxia was linked to mouse chromosome 1 (logarithm of the odds ratio = 4.4) in an interval between 68 and 89 cM (i.e., between D1Mit14 and D1Mit291). The second quantitative trait loci linked differences in CO(2) potentiation to mouse chromosome 5 (logarithm of the odds ratio = 3.7) in a region between 7 and 29 cM (i.e., centered at D5Mit66). In conclusion, these results support the hypothesis that a minimum of two significant genes modulate the interactive effects of hypoxia and hypercapnia in this genetic model.

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Interactions in hypoxic and hypercapnic breathing are genetically linked to mouse chromosomes 1 and 5

Tankersley¹,

Broman

2004

Journal of Applied Physiology

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“…It is generally accepted that human subjects show an increased hypercapnic ventilatory response when the O 2 tension is simultaneously lowered (Tatsumi et al 1986;Masuda et al 2001;Sovik et al 2004). This positive interaction has been confirmed in recent studies carried out on goats, lambs, piglets, cats, rats, and mice (Daristotle et al 1987;Wolsink et al 1992;Carroll et al 1993;Tankersley et al 1994Tankersley et al , 2004Pepper et al 1995;Calder et al 1997), although some early studies showed a negative interaction in cats (Ou et al 1976).…”

Section: Chronic Cs Exposure Produced An Abnormal Inhibitory Interactmentioning

confidence: 99%

Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke-induced emphysema

Zhuang

Wang

et al. 2007

Respiratory Physiology & Neurobiology

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It has been reported that the degree of emphysema induced by chronic cigarette smoke (CS) is greater in female C3H/HeN mice as compared to other mouse strains. We hypothesized that these mice would develop the similar major characteristics seen in hypercapnic patients with chronic obstructive pulmonary disease (COPD), including emphysema, pulmonary inflammation, hypercapnia/ hypoxemia, rapid breathing, and attenuated ventilatory response (AVR). Mice were exposed either to CS or filtered air (FA) for 16 wk. After exposure, arterial blood gases and minute ventilation were measured before and during chemical challenges in anesthetized and spontaneously breathing mice. We found that as compared to FA, CS exposure caused emphysema and pulmonary inflammation associated with: (1) hypercapnia and hypoxemia, (2) rapid breathing, and (3) AVR to 25 breaths of pure N 2 , 5% CO 2 alone, and 5% CO 2 coupled with 10% O 2 . The similarity of these pathophysiological characteristics between our mouse model and COPD patients suggests that this model could be effectively applied to study COPD pathophysiology, especially central mechanisms of the AVR genesis.

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“…Nonlinear interaction between PCO 2 and PO 2 , i.e. increased CO 2 chemosensitivity at increasing levels of hypoxia, has been described in carotid and aortic nerve recordings (7,8,16) and in ventilatory responses in animals (17,18) and adult humans (19). Whether interaction between PCO 2 and PO 2 is present at birth and whether it increases postnatally differs from one species to another (7,16,20).…”

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confidence: 99%

Development of Ventilatory Response to Transient Hypercapnia and Hypercapnic Hypoxia in Term Infants

Søvik

Lossius

2004

Pediatr Res

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Whereas peripheral chemoreceptor oxygen sensitivity increases markedly after birth, previous studies of ventilatory responses to CO 2 in term infants have shown no postnatal development. However, the hypercapnic challenges applied have usually been long-term, which meant that the effect of central chemoreceptors dominated. Oscillatory breathing, apneas, and sighs cause transient PCO 2 changes, probably primarily stimulating peripheral chemoreceptors. We wanted to assess whether the immediate ventilatory responses to step changes in inspired CO 2 and O 2 in term infants undergo postnatal developmental changes. Twenty-six healthy term infants were studied during natural sleep 2 d and 8 wk postnatally. Ventilatory responses to a randomized sequence of 15 s hypercapnia (3% CO 2 ), hypoxia (15% O 2 ), and hypercapnic hypoxia (3% CO 2 ϩ 15% O 2 ) were recorded breath-by-breath using a pneumotachometer. Response rate, stimulus-response time, and response magnitude were analyzed with ANOVA after coherent averaging. Response rate increased with age by 30% (hypercapnia), 318% (hypoxia), and 302% (hypercapnic hypoxia). Response rate during hypercapnic hypoxia exceeded rate during hypercapnia plus rate during hypoxia in wk 8, but not on d 2. Time to half-maximum response decreased by 3.4 s with age for the two hypercapnic stimuli but was unchanged for hypoxia. Response magnitude was unchanged for hypercapnia, but increased for the two hypoxic stimuli. In conclusion, an interaction between the effects of hypercapnia and hypoxia on ventilatory response rate emerged between postnatal d 2 and wk 8 in term infants. Concomitantly, stimulus-response time to hypercapnic stimuli declined markedly. Peripheral and central chemoreceptors are crucial for the precise control of respiration. The carotid, aortic, and central chemoreceptors are functional even in fetal life (1, 2), but the transition to continuous breathing calls for rapid adjustments. The marked increase in arterial PO 2 at birth brings about a corresponding resetting of carotid and aortic chemoreceptor O 2 sensitivity, which takes place during the first postnatal days and weeks (1,(3)(4)(5). In contrast, studies of postnatal CO 2 chemosensitivity show divergent results. Steady-state CO 2 sensitivity increased after birth in some (6 -8) but not all species (9). Preterm infants displayed an age-related increase in steady-state CO 2 sensitivity (10, 11), whereas term infants showed no such postnatal development (12, 13). Dynamic CO 2 sensitivity was unchanged during the first month in neonatal lambs (8,14), whereas in piglets the relative contribution of peripheral chemoreceptors to CO 2 stimulation increased postnatally (15).Ultimately, the combined effects of PCO 2 , arterial PO 2 , and pH determine the level of ventilation. Nonlinear interaction between PCO 2 and PO 2 , i.e. increased CO 2 chemosensitivity at increasing levels of hypoxia, has been described in carotid and aortic nerve recordings (7,8,16) and in ventilatory responses in animals (17, 18) and adult humans (1...

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Lack of positive interaction between CO2 and hypoxic stimulation for PCO2–VAS response slope in humans

Cited by 20 publications

References 37 publications

Interactions in hypoxic and hypercapnic breathing are genetically linked to mouse chromosomes 1 and 5

Interactions in hypoxic and hypercapnic breathing are genetically linked to mouse chromosomes 1 and 5

Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke-induced emphysema

Development of Ventilatory Response to Transient Hypercapnia and Hypercapnic Hypoxia in Term Infants

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