Measuring central-chemoreflex sensitivity in man: rebreathing and steady-state methods compared

Mohan, Ravi; Amara, Catherine E.; Cunningham, David A.; Duffin, James

doi:10.1016/s0034-5687(99)00003-1

Cited by 75 publications

(90 citation statements)

References 17 publications

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“…A comprehensive critique of the modified rebreathing procedure has been described in previous reports (8,14,17,18,20). A limitation of the present study is that it used a cross-sectional approach to examine the effects of pregnancy on the ventilatory response to CO 2 .…”

Section: Discussionmentioning

confidence: 99%

Effects of human pregnancy on the ventilatory chemoreflex response to carbon dioxide

Jensen¹,

Wolfe²,

Slatkovska³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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This study examined the effects of human pregnancy on the central chemoreflex control of breathing. Subjects were two groups ( n = 11) of pregnant subjects (PG, gestational age, 36.5 ± 0.4 wk) and nonpregnant control subjects (CG), equated for mean age, body height, prepregnant body mass, parity, and aerobic fitness. All subjects performed a hyperoxic CO2 rebreathing procedure, which includes prior hyperventilation and maintenance of iso-oxia. Resting blood gases and plasma progesterone and estradiol concentrations were measured. During rebreathing trials, end-tidal Pco2 increased, whereas end-tidal Po2 was maintained at a constant hyperoxic level. The point at which ventilation (V̇e) began to rise as end-tidal Pco2 increased was identified as the central chemoreflex ventilatory recruitment threshold for CO2 (VRTco2). V̇e levels below (basal V̇e) and above (central chemoreflex sensitivity) the VRTco2 were determined. The VRTco2 was significantly lower in the PG vs. CG (40.5 ± 0.8 vs. 45.8 ± 1.6 Torr), and both basal V̇e (14.8 ± 1.1 vs. 9.3 ± 1.6 l/min) and central chemoreflex sensitivity (5.07 ± 0.74 vs. 3.16 ± 0.29 l·min−1·Torr−1) were significantly higher in the PG vs. CG. Pooled data from the two groups showed significant correlations for resting arterial Pco2 with basal V̇e, central chemoreflex sensitivity, and the VRTco2. The VRTco2 was also correlated with progesterone and estradiol concentrations. These data support the hypothesis that pregnancy decreases the threshold and increases the sensitivity of the central chemoreflex response to CO2. These changes may be due to the effects of gestational hormones on chemoreflex and/or nonchemoreflex drives to breathe.

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Section: Discussionmentioning

confidence: 99%

Effects of human pregnancy on the ventilatory chemoreflex response to carbon dioxide

Jensen¹,

Wolfe²,

Slatkovska³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Thus, to examine ventilatory effects of central chemoreceptor stimulation, we used hyperoxic hypercapnia. This setting of hyperoxia along with hypercapnia was used to minimize the effect of peripheral chemoreceptors (38) and maximize the effects on central chemoreceptors. Hypoxia exerts its effects mainly via the peripheral receptors comprising the carotid and aortic bodies.…”

Section: Discussionmentioning

confidence: 99%

Ventilatory baroreflex sensitivity in humans is not modulated by chemoreflex activation

Stewart

Rivera²,

Clarke³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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IL, Ocon AJ, Taneja I, Terilli C, Medow MS. Ventilatory baroreflex sensitivity in humans is not modulated by chemoreflex activation. Am J Physiol Heart Circ Physiol 300: H1492-H1500, 2011. First published February 11, 2011 doi:10.1152/ajpheart.01217.2010.-Increasing arterial blood pressure (AP) decreases ventilation, whereas decreasing AP increases ventilation in experimental animals. To determine whether a "ventilatory baroreflex" exists in humans, we studied 12 healthy subjects aged 18 -26 yr. Subjects underwent baroreflex unloading and reloading using intravenous bolus sodium nitroprusside (SNP) followed by phenylephrine ("Oxford maneuver") during the following "gas conditions:" room air, hypoxia (10% oxygen)-eucapnia, and 30% oxygen-hypercapnia to 55-60 Torr. Mean AP (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), expiratory minute ventilation (V E), respiratory rate (RR), and tidal volume were measured. After achieving a stable baseline for gas conditions, we performed the Oxford maneuver. V E increased from 8.8 Ϯ 1.3 l/min in room air to 14.6 Ϯ 0.8 l/min during hypoxia and to 20.1 Ϯ 2.4 l/min during hypercapnia, primarily by increasing tidal volume. V E doubled during SNP. CO increased from 4.9 Ϯ .3 l/min in room air to 6.1 Ϯ .6 l/min during hypoxia and 6.4 Ϯ .4 l/min during hypercapnia with decreased TPR. HR increased for hypoxia and hypercapnia. Sigmoidal ventilatory baroreflex curves of V E versus MAP were prepared for each subject and each gas condition. Averaged curves for a given gas condition were obtained by averaging fits over all subjects. There were no significant differences in the average fitted slopes for different gas conditions, although the operating point varied with gas conditions. We conclude that rapid baroreflex unloading during the Oxford maneuver is a potent ventilatory stimulus in healthy volunteers. Tidal volume is primarily increased. Ventilatory baroreflex sensitivity is unaffected by chemoreflex activation, although the operating point is shifted with hypoxia and hypercapnia.baroreceptors; ventilation; blood pressure In intact animals (dogs) hyperpnea follows occlusion of the common carotid arteries; it is wholly reflex in origin because the effect is the same even though all branches of the carotids have been previously tied excepting only the lingual arteries, and because section of the sinus nerves completely abolishes the reaction.Carl F. Schmidt (45) DETECTION OF ARTERIAL BLOOD PRESSURE (AP) by the arterial baroreceptors causes changes in heart rate (HR), sympathetic vasoconstriction, adrenal function, and renal sympathetic activity (2, 5). Evidence primarily derived from animal experiments suggests that the carotid sinus baroreflex also affects respiratory function (7,26,45,48). Rapidly increasing blood pressure causes decreased ventilation, whereas decreasing blood pressure causes increased ventilation. While these ventilatory effects were at one time attributed to increased or decreased perfusion of the arterial chemoreceptors (26, 32), s...

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“…The presence of CO 2 in the rebreathing gas is crucial; it serves to effectively clamp arterial pCO 2 (p ET CO 2 ) at the value of venous pCO 2 (tissue pCO 2 ). Only under this condition does p ET CO 2 provide a reasonable measure of CNS pCO 2 , while the relationship between p ET CO 2 and V E provides a monitor of central ventilatory control (18,21).…”

Section: Discussionmentioning

confidence: 99%

Interaction of Ritonavir-Boosted Tipranavir with Loperamide Does Not Result in Loperamide-Associated Neurologic Side Effects in Healthy Volunteers

Mukwaya

MacGregor

Hoelscher

et al. 2005

Antimicrob Agents Chemother

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Loperamide (LOP) is a peripherally acting opioid receptor agonist used for the management of chronic diarrhea through the reduction of gut motility. The lack of central opioid effects is partly due to the efflux activity of the multidrug resistance transporter P-glycoprotein (P-gp) at the blood-brain barrier. The protease inhibitors are substrates for P-gp and have the potential to cause increased LOP levels in the brain. Because protease inhibitors, including tipranavir (TPV), are often associated with diarrhea, they are commonly used in combination with LOP. The level of respiratory depression, the level of pupil constriction, the pharmacokinetics, and the safety of LOP alone compared with those of LOP-ritonavir (RTV), LOP-TPV, and LOP-TPV-RTV were evaluated in a randomized, open-label, parallel-group study with 24 healthy human immunodeficiency virus type 1-negative adults. Respiratory depression was assessed by determination of the ventilatory response to carbon dioxide. Tipranavir-containing regimens (LOP-TPV and LOP-TPV-RTV) caused decreases in the area under the concentration-time curve from time zero to infinity for LOP (51% and 63% decreases, respectively) and its metabolite (72% and 77% decreases, respectively), whereas RTV caused increases in the levels of exposure of LOP (121% increase) and its metabolite (44% increase). In vitro and in vivo data suggest that TPV is a substrate for and an inducer of P-gp activity. The respiratory response to LOP in combination with TPV and/or RTV was not different from that to LOP alone. There was no evidence that LOP had opioid effects in the central nervous system, as measured indirectly by CO 2 response curves and pupillary response in the presence of TPV and/or RTV.Loperamide (LOP; Imodium, McNeil-PPC, Inc.) is a peripherally acting opioid receptor agonist that reduces gut motility and that is used for the management of chronic diarrhea (8,25). The principal metabolic fate of loperamide in humans involves oxidative N-dealkylation to N-demethyl-loperamide as the principal metabolite. In human liver microsomes, cytochrome P450 3A4 (CYP3A4) appears to be the major isozyme responsible for loperamide metabolism, with minor contributions from CYP2B6 (9). At the doses used to control diarrhea, LOP has very poor penetration of the blood-brain barrier and produces no central opioid effects, such as respiratory depression, pupillary constrictions, analgesia, or changes in alertness (26). The poor central nervous system (CNS) penetration is attributed both to LOP active cellular efflux via the multidrug resistance transporter P-glycoprotein (P-gp) in the blood-brain barrier and to low systemic oral bioavailability (24). When P-gp is inhibited, LOP and its metabolites may potentially enter the brain and cause opioid-induced central neurological adverse events (AEs) (23, 24).Current treatment for human immunodeficiency virus type 1 (HIV-1) infection consists of a combination of antiretroviral agents of different classes. Tipranavir (TPV) is a potent nonpeptidic HIV-1 and HIV-...

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Measuring central-chemoreflex sensitivity in man: rebreathing and steady-state methods compared

Cited by 75 publications

References 17 publications

Effects of human pregnancy on the ventilatory chemoreflex response to carbon dioxide

Effects of human pregnancy on the ventilatory chemoreflex response to carbon dioxide

Ventilatory baroreflex sensitivity in humans is not modulated by chemoreflex activation

Interaction of Ritonavir-Boosted Tipranavir with Loperamide Does Not Result in Loperamide-Associated Neurologic Side Effects in Healthy Volunteers

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