Defining origin of positive slope in hypercapnic ventilatory response curve

1991 ◽  
Vol 261 (3) ◽  
pp. R747-R751
Author(s):  
Z. Lorinc ◽  
J. Derr ◽  
M. Snider ◽  
R. Lydic
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Complex Function ◽  
Co2 Concentration ◽  
Positive Slope ◽  
Hypercapnic Ventilatory Response ◽  
Joint Point ◽  
Respiratory Stimulant ◽  
End Tidal ◽  
Derived Data

The sensitivity to CO2 as a respiratory stimulant has traditionally been studied by exposing organisms to progressively increasing levels of inspired CO2 while measuring the corresponding increase in minute ventilation (V). Plots of V as a function of end-tidal CO2 concentration reveal a complex function with a "dogleg" shape. Only the positive slope of the V function is taken as an index of chemosensitivity, but the starting points for such analyses are often chosen arbitrarily. This paper examined the hypotheses that the range of CO2 concentrations over which V slopes are compared may be mathematically defined and that arbitrary choices of this analytic range may influence conclusions about the hypercapnic ventilatory response (HCVR). Three mathematical models attempted to define the origin of the positive slope for the HCVR curve using empirically derived data. The results revealed good agreement that the origin of the positive HCVR slope may be reliably defined by a point that joins the horizontal and positive slope of the HCVR curve. In addition to identifying the "joint-point" statistic, the results suggest that arbitrarily defining the range of CO2 values over which V is analyzed can be replaced by quantitative approaches for identifying the origin of the ventilatory response to hypercapnia.

Ventilatory responses to hypercapnia and hypoxia during continuous aspirin ingestion

1977 ◽  
Vol 43 (6) ◽  
pp. 971-976 ◽  
Author(s):  
D. J. Riley ◽  
B. A. Legawiec ◽  
T. V. Santiago ◽  
N. H. Edelman
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Normal Subjects ◽  
Carbon Dioxide Tension ◽  
Base Line ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Responses ◽  
Hypercapnic Ventilatory Response ◽  
The Central Nervous System ◽  
End Tidal

Hypercapnic and hypoxic ventilatory responses were serially measured in nine normal subjects given 3.9 g aspirin (ASA) per day for 9 days. Minute ventilation (VE), end-tidal carbon dioxide tension (PETCO2), venous bicarbonate concentration [HCO3-], oxygen consumption (VO2), hypercapnic ventilatory response (deltaVE/deltaPCO2), and isocapnic hypoxic ventilatory response (A) were determined before, 2 h after the first dose, and at 72-h intervals during the next 14 days. Serum salicylate levels averaged 18.6 +/- 2.0 mg/dl. VE increased (P less than 0.05, PETCO2 decreased (P less than 0.05), and [HCO3-] did not change significantly during drug ingestion. deltaVE/deltaPCO2 increased gradually to a value 37% greater than control by day 3 and remained constant (P less 0.01). A increased by 251% and VO2 by 18% within 2 h and remained constant for the remainder of the ASA period (P less than 0.01). All values returned to base line within 24 h following cessation of ASA. We conclude that during continuous ASA ingestion there is a gradual increase of hypercapnic ventilatory response. This may reflect slow entrance of ASA into the central nervous system. In contrast, there is a rapid rise in hypoxic ventilatory response which may be mechanically linked to changes in metabolic rate.

Living high-training low increases hypoxic ventilatory response of well-trained endurance athletes

2002 ◽  
Vol 93 (4) ◽  
pp. 1498-1505 ◽  
Author(s):  
Nathan E. Townsend ◽  
Christopher J. Gore ◽  
Allan G. Hahn ◽  
Michael J. McKenna ◽  
Robert J. Aughey ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Endurance Athletes ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Hypoxic Ventilatory Response ◽  
Ambient Conditions ◽  
Altitude Exposure ◽  
End Tidal

This study determined whether “living high-training low” (LHTL)-simulated altitude exposure increased the hypoxic ventilatory response (HVR) in well-trained endurance athletes. Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxic exposure (LHTLc, n = 12), 20 nights of intermittent hypoxic exposure (four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia, LHTLi, n = 10), or control (Con, n = 11). LHTLc and LHTLi slept 8–10 h/day overnight in normobaric hypoxia (∼2,650 m); Con slept under ambient conditions (600 m). Resting, isocapnic HVR (ΔV˙e/ΔSpO2 , whereV˙e is minute ventilation and SpO2 is blood O2 saturation) was measured in normoxia before hypoxia (Pre), after 1, 3, 10, and 15 nights of exposure (N1, N3, N10, and N15, respectively), and 2 nights after the exposure night 20 (Post). Before each HVR test, end-tidal Pco 2(Pet CO2 ) and V˙e were measured during room air breathing at rest. HVR (l · min−1 · %−1) was higher ( P < 0.05) in LHTLc than in Con at N1 (0.56 ± 0.32 vs. 0.28 ± 0.16), N3 (0.69 ± 0.30 vs. 0.36 ± 0.24), N10 (0.79 ± 0.36 vs. 0.34 ± 0.14), N15 (1.00 ± 0.38 vs. 0.36 ± 0.23), and Post (0.79 ± 0.37 vs. 0.36 ± 0.26). HVR at N15 was higher ( P < 0.05) in LHTLi (0.67 ± 0.33) than in Con and in LHTLc than in LHTLi. Pet CO2 was depressed in LHTLc and LHTLi compared with Con at all points after hypoxia ( P < 0.05). No significant differences were observed for V˙e at any point. We conclude that LHTL increases HVR in endurance athletes in a time-dependent manner and decreases Pet CO2 in normoxia, without change inV˙e. Thus endurance athletes sleeping in mild hypoxia may experience changes to the respiratory control system.

Gas exchange in nonperfused dog lungs

1981 ◽  
Vol 51 (5) ◽  
pp. 1261-1267 ◽  
Author(s):  
J. W. Shepard ◽  
V. D. Minh ◽  
G. F. Dolan
Keyword(s):  
Gas Exchange ◽  
Minute Ventilation ◽  
Left Lung ◽  
Co2 Concentration ◽  
Gas Transfer ◽  
O2 Uptake ◽  
Tissue Metabolism ◽  
End Tidal

Gas exchange was studied under conditions of zero perfusion both in situ and in vitro. Six dogs, anesthetized with pentobarbital sodium, underwent surgical interruption of both pulmonary and bronchial circulations to the left lung. Despite the absence of perfusion, O2 uptake for the left lung ranged from 0.76 to 0.98 ml/min, whereas CO2 elimination greatly exceeded O2 uptake ranging from 1.68 to 4.34 ml/min. In addition, CO2 output was observed to vary directly with the level of minute ventilation (VE) and inversely with end-tidal CO2 concentration. To investigate the mechanisms responsible for these findings we studied 20 excised, ventilated, but nonperfused dog lungs to evaluate the relative roles of tissue metabolism and transpleural diffusion to gas exchange. The results obtained with these excised lungs under conditions of varying VE and extrapleural gas concentrations indicate that the high respiratory exchange ratios observed in situ can be explained by the greater rate with which CO2 diffuses through the pleura, and that reduced ventilation decreases total gas transfer by decreasing the transpleural partial pressure driving gradient. Our data further document that the concentration of CO2 in alveolar gas may differ significantly from that present in inspired gas under conditions of ventilation-perfusion ratio equal to infinity, and that tissue metabolism as well as transpleural diffusion contribute to gas exchange in nonperfused lung.

Ventilatory responses to carbon dioxide at low and high levels of oxygen are elevated after episodic hypoxia in men compared with women

2004 ◽  
Vol 97 (5) ◽  
pp. 1673-1680 ◽  
Author(s):  
Chris Morelli ◽  
M. Safwan Badr ◽  
Jason H. Mateika
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
High Oxygen ◽  
Set Point ◽  
Ventilatory Responses ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Oxygen Gas ◽  
End Tidal

We hypothesized that the acute ventilatory response to carbon dioxide in the presence of low and high levels of oxygen would increase to a greater extent in men compared with women after exposure to episodic hypoxia. Eleven healthy men and women of similar race, age, and body mass index completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the end-tidal partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr), or high oxygen gas mixture (150 Torr). During the trials, PetCO2 increased while the selected level of oxygen was maintained. The point at which minute ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the carbon dioxide set point. The ventilatory response below and above this point was determined. The results showed that the ventilatory response to carbon dioxide above the set point was increased in men compared with women before exposure to episodic hypoxia, independent of the oxygen level that was maintained during the rebreathing trials (50 Torr: men, 5.19 ± 0.82 vs. women, 4.70 ± 0.77 l·min−1·Torr−1; 150 Torr: men, 4.33 ± 1.15 vs. women, 3.21 ± 0.58 l·min−1·Torr−1). Moreover, relative to baseline measures, the ventilatory response to carbon dioxide in the presence of low and high oxygen levels increased to a greater extent in men compared with women after exposure to episodic hypoxia (50 Torr: men, 9.52 ± 1.40 vs. women, 5.97 ± 0.71 l·min−1·Torr−1; 150 Torr: men, 5.73 ± 0.81 vs. women, 3.83 ± 0.56 l·min−1·Torr−1). Thus we conclude that enhancement of the acute ventilatory response to carbon dioxide after episodic hypoxia is sex dependent.

Effect of intravenous dopamine on hypercapnic ventilatory response in humans

1983 ◽  
Vol 55 (5) ◽  
pp. 1418-1425 ◽  
Author(s):  
D. S. Ward ◽  
J. W. Bellville
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Carbon Dioxide Concentration ◽  
Carbon Dioxide Tension ◽  
Model Parameters ◽  
Loop Gain ◽  
Loop Contribution ◽  
Dopamine Infusion ◽  
Hypercapnic Ventilatory Response ◽  
End Tidal

This study assessed the effect of low-dose intravenous dopamine (3 micrograms X kg-1 X min-1) on the hypercapnic ventilatory response in humans. Six normal healthy subjects were studied. By manipulating the inspired carbon dioxide concentration, the end-tidal carbon dioxide tension was raised in a stepwise fashion from 41 to 49 Torr and held at this level for 4 min. The end-tidal CO2 tension was then lowered back to 41 Torr in a stepwise fashion. The end-tidal O2 tension was held constant at 106 Torr throughout the experiment. The ventilatory response to this normoxic hypercapnic stimulus was analyzed by fitting two exponential functions, allowing the response to be separated into slow and fast chemoreflex loops. Each loop is described by a gain, time constant, and time delay. A single eupneic threshold was used for both loops. Nine control experiments and eight experiments performed during dopamine infusion were analyzed. The dopamine infusion caused the fast loop gain to be significantly (P less than 0.05) reduced from 0.64 to 0.19 l X min-1 X Torr-1, while the slow loop gain was unchanged. The fast loop contribution was reduced from 28 to 11% of the total ventilatory response. None of the other model parameters were significantly affected by the dopamine infusion. Exogenously administered dopamine substantially reduces the sensitivity of the fast chemoreflex loop to carbon dioxide.

Ventilatory response to exercise in diabetic subjects with autonomic neuropathy

1996 ◽  
Vol 81 (5) ◽  
pp. 1978-1986 ◽  
Author(s):  
C. Tantucci ◽  
P. Bottini ◽  
M. L. Dottorini ◽  
E. Puxeddu ◽  
G. Casucci ◽  
...  
Keyword(s):  
Respiratory Rate ◽  
Autonomic Neuropathy ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Control Subjects ◽  
Inhibitory Modulation ◽  
End Tidal ◽  
And Control ◽  
Response To Exercise ◽  
Maximal Voluntary Ventilation

Tantucci, C., P. Bottini, M. L. Dottorini, E. Puxeddu, G. Casucci, L. Scionti, and C. A. Sorbini. Ventilatory response to exercise in diabetic subjects with autonomic neuropathy. J. Appl. Physiol. 81(5): 1978–1986, 1996.—We have used diabetic autonomic neuropathy as a model of chronic pulmonary denervation to study the ventilatory response to incremental exercise in 20 diabetic subjects, 10 with (Dan+) and 10 without (Dan−) autonomic dysfunction, and in 10 normal control subjects. Although both Dan+ and Dan− subjects achieved lower O2 consumption and CO2 production (V˙co 2) than control subjects at peak of exercise, they attained similar values of either minute ventilation (V˙e) or adjusted ventilation (V˙e/maximal voluntary ventilation). The increment of respiratory rate with increasing adjusted ventilation was much higher in Dan+ than in Dan− and control subjects ( P < 0.05). The slope of the linearV˙e/V˙co 2relationship was 0.032 ± 0.002, 0.027 ± 0.001 ( P < 0.05), and 0.025 ± 0.001 ( P < 0.001) ml/min in Dan+, Dan−, and control subjects, respectively. Both neuromuscular and ventilatory outputs in relation to increasingV˙co 2 were progressively higher in Dan+ than in Dan− and control subjects. At peak of exercise, end-tidal [Formula: see text] was much lower in Dan+ (35.9 ± 1.6 Torr) than in Dan− (42.1 ± 1.7 Torr; P < 0.02) and control (42.1 ± 0.9 Torr; P < 0.005) subjects. We conclude that pulmonary autonomic denervation affects ventilatory response to stressful exercise by excessively increasing respiratory rate and alveolar ventilation. Reduced neural inhibitory modulation from sympathetic pulmonary afferents and/or increased chemosensitivity may be responsible for the higher inspiratory output.

scholarly journals Activation of Opioid μ Receptors in Caudal Medullary Raphe Region Inhibits the Ventilatory Response to Hypercapnia in Anesthetized Rats

2007 ◽  
Vol 107 (2) ◽  
pp. 288-297 ◽  
Author(s):  
Zhenxiong Zhang ◽  
Fadi Xu ◽  
Cancan Zhang ◽  
Xiaomin Liang
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Central Area ◽  
Mu Receptor ◽  
Medullary Raphe ◽  
Mu Receptors ◽  
End Tidal ◽  
Spontaneously Breathing ◽  
Made In

Background : Opioids, extensively used as analgesics, markedly depress ventilation, particularly the ventilatory responsiveness to hypercapnia in humans and animals predominantly via acting on mu receptors. The medullary raphe region (MRR) contains abundant mu receptors responsible for analgesia and is also an important central area involving carbon dioxide chemoreception and contributing to the ventilatory responsiveness to hypercapnia. Therefore, the authors asked whether activation of mu receptors in the caudal, medial, or rostral MRR depressed ventilation and the response to hypercapnia, respectively. Methods : Experiments were conducted in 32 anesthetized and spontaneously breathing rats. Ventilation and it response to progressive hypercapnia were recorded. The slopes obtained from plotting minute ventilation, respiratory frequency, and tidal volume against the corresponding levels of end-tidal pressure of carbon dioxide were used as the indices of the respiratory responsiveness to carbon dioxide. DAMGO ([d-Ala2, N-Me-Phe4, Gly-ol]-enkephalin), a mu-receptor agonist, was systemically administered (100 mug/kg) before and/or after local injection of CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (100 ng/100 nl), a mu-receptor antagonist, into the caudal MRR, or locally administered (35 ng/100 nl) into the MRR subnuclei. Results : The authors found that systemic DAMGO significantly inhibited ventilation and the response to carbon dioxide by 20% and 31%, respectively, and these responses were significantly diminished to 11% and 14% after pretreatment of the caudal MRR with CTAP. Local administration of DAMGO into the caudal MRR also reduced ventilation and the response to carbon dioxide by 22% and 28%, respectively. In sharp contrast, these responses were not observed when the DAMGO microinjection was made in the middle MRR or rostral MRR. Conclusions : These results lead to the conclusion that mu receptors in the caudal MRR rather than the middle MRR or rostral MRR are important but not exclusive for attenuating the hypercapnic ventilatory response.

Somatostatin inhibits the ventilatory response to hypoxia in humans

1986 ◽  
Vol 60 (3) ◽  
pp. 997-1002 ◽  
Author(s):  
D. L. Maxwell ◽  
P. Chahal ◽  
K. B. Nolop ◽  
J. M. Hughes
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Open Circuit ◽  
Co2 Production ◽  
Adult Males ◽  
Hypoxic Response ◽  
Ventilatory Responses ◽  
End Tidal ◽  
Hypercapnic Response ◽  
Ventilatory Response To Hypoxia

The effects of a 90-min infusion of somatostatin (1 mg/h) on ventilation and the ventilatory responses to hypoxia and hypercapnia were studied in six normal adult males. Minute ventilation (VE) was measured with inductance plethysmography, arterial 02 saturation (SaO2) was measured with ear oximetry, and arterial PCO2 (Paco2) was estimated with a transcutaneous CO2 electrode. The steady-state ventilatory response to hypoxia (delta VE/delta SaO2) was measured in subjects breathing 10.5% O2 in an open circuit while isocapnia was maintained by the addition of CO2. The hypercapnic response (delta VE/delta PaCO2) was measured in subjects breathing first 5% and then 7.5% CO2 (in 52–55% O2). Somatostatin greatly attenuated the hypoxic response (control mean -790 ml x min-1.%SaO2 -1, somatostatin mean -120 ml x min-1.%SaO2 -1; P less than 0.01), caused a small fall in resting ventilation (mean % fall - 11%), but did not affect the hypercapnic response. In three of the subjects progressive ventilatory responses (using rebreathing techniques, dry gas meter, and end-tidal Pco2 analysis) and overall metabolism were measured. Somatostatin caused similar changes (mean fall in hypoxic response -73%; no change in hypercapnic response) and did not alter overall O2 consumption nor CO2 production. These results show an hitherto-unsuspected inhibitory potential of this neuropeptide on the control of breathing; the sparing of the hypercapnic response is suggestive of an action on the carotid body but does not exclude a central effect.

Increased chemoreceptor output and ventilatory response to sustained hypoxia

1989 ◽  
Vol 67 (3) ◽  
pp. 1157-1163 ◽  
Author(s):  
D. Georgopoulos ◽  
S. Walker ◽  
N. R. Anthonisen
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Base Line ◽  
Breathing Patterns ◽  
Peripheral Chemoreceptor ◽  
Depressant Action ◽  
Before And After ◽  
End Tidal ◽  
Arterial O2 Saturation ◽  
Sustained Hypoxia

In adult humans the ventilatory response to sustained hypoxia (VRSH) is biphasic, characterized by an initial brisk increase, due to peripheral chemoreceptor (PC) stimulation, followed by a decline attributed to central depressant action of hypoxia. To study the effects of selective stimulation of PC on the ventilatory response pattern to hypoxia, the VRSH was evaluated after pretreatment with almitrine (A), a PC stimulant. Eight subjects were pretreated with A (75 mg po) or placebo (P) on 2 days in a single-blind manner. Two hours after drug administration, they breathed, in succession, room air (10 min), O2 (5 min), room air (5 min), hypoxia [25 min, arterial O2 saturation (SaO2) = 80%], O2 (5 min), and room air (5 min). End-tidal CO2 was kept constant at the normoxic base-line values. Inspiratory minute ventilation (VI) and breathing patterns were measured over the last 2 min of each period and during minutes 3–5 of hypoxia, and nadirs in VI were assessed just before and after O2 exposure. Independent of the day, the VRSH was biphasic. With P and A pretreatment, early hypoxia increased VI 4.6 +/- 1 and 14.2 +/- 1 (SE) l/min, respectively, from values obtained during the preceding room-air period. On A day the hypoxic ventilatory decline was significantly larger than that on P day, and on both days the decline was a constant fraction of the acute hypoxic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of testosterone on the apneic threshold in women during NREM sleep

2003 ◽  
Vol 94 (1) ◽  
pp. 101-107 ◽  
Author(s):  
X. S. Zhou ◽  
J. A. Rowley ◽  
F. Demirovic ◽  
M. P. Diamond ◽  
M. S. Badr
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Premenopausal Women ◽  
Nrem Sleep ◽  
Central Apnea ◽  
Rapid Eye Movement Sleep ◽  
A Value ◽  
Before And After ◽  
Testosterone Administration ◽  
End Tidal

The hypocapnic apneic threshold (AT) is lower in women relative to men. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during non-rapid eye movement sleep in eight healthy, nonsnoring, premenopausal women before and after 10–12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 min with tidal volumes ranging from 175 to 215% above eupneic tidal volume and respiratory frequency matched to eupneic frequency. Cessation of MV resulted in hypocapnic central apnea or hypopnea depending on the magnitude of hypocapnia. Nadir minute ventilation as a percentage of control (%V˙e) was plotted against the change in end-tidal CO2(Pet CO2 ); %V˙e was given a value of zero during central apnea. The AT was defined as the Pet CO2 at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression V˙e vs. Pet CO2 . Both the AT (39.5 ± 2.9 vs. 42.1 ± 3.0 Torr; P = 0.002) and HPVR (0.20 ± 0.05 vs. 0.33 ± 0.11%V˙e/Torr; P = 0.016) increased with testosterone administration. We conclude that testosterone administration increases AT in premenopausal women, suggesting that the increased breathing instability during sleep in men is related to the presence of testosterone.

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