Variable inhibition by falling CO2 of hypoxic ventilatory response in humans

1984 ◽  
Vol 56 (1) ◽  
pp. 207-210 ◽  
Author(s):  
L. G. Moore ◽  
S. Y. Huang ◽  
R. E. McCullough ◽  
J. B. Sampson ◽  
J. T. Maher ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Hypoxic Ventilatory Response ◽  
Co2 Response ◽  
Low Co2 ◽  
Two Factors ◽  
Variable Extent ◽  
The Difference ◽  
End Tidal ◽  
Ventilatory Response To Co2

Acute hypoxia stimulates an increase in ventilation but the resulting hypocapnia limits the magnitude of the increase. Thus the hypoxic ventilatory response is usually measured during isocapnia, but this may not reflect events at high altitude. We hypothesized that the degree of inhibition by hypocapnia might depend on individual ventilatory response to CO2 and thus vary between persons. To test this hypothesis we compared the isocapnic hypoxic ventilatory response (end-tidal PCO2 maintained by CO2 addition) with the response in which CO2 was not added and the end-tidal PCO2 fell to a variable extent (poikilocapnic hypoxia). In 14 healthy persons we found that the poikilocapnic hypoxic ventilatory response was determined by two factors: sensitivity to isocapnic hypoxia acting to increase ventilation and sensitivity to CO2 acting to decrease the hypoxic ventilatory response. The ventilatory response to poikilocapnic hypoxia correlated with but was generally less than the isocapnic hypoxic response. The magnitude of the difference between them related to the hypercapnic response. Further, the results suggested that the CO2 response in the high CO2 range related to ventilatory events in the low CO2 range. Thus the magnitude of ventilatory inhibition by hypocapnia may depend on individual ventilatory responsiveness to CO2.

Respiratory control in humans after 8 h of lowered arterial Po 2, hemodilution, or carboxyhemoglobinemia

2001 ◽  
Vol 90 (4) ◽  
pp. 1189-1195 ◽  
Author(s):  
Xiaohui Ren ◽  
Keith L. Dorrington ◽  
Peter A. Robbins
Keyword(s):  
Oxygen Content ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Venous Blood ◽  
Respiratory Control ◽  
Progressive Increase ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Arterial Oxygen Content ◽  
End Tidal

In humans exposed to 8 h of isocapnic hypoxia, there is a progressive increase in ventilation that is associated with an increase in the ventilatory sensitivity to acute hypoxia. To determine the relative roles of lowered arterial Po 2 and oxygen content in generating these changes, the acute hypoxic ventilatory response was determined in 11 subjects after four 8-h exposures: 1) protocol IH (isocapnic hypoxia), in which end-tidal Po 2 was held at 55 Torr and end-tidal Pco 2 was maintained at the preexposure value; 2) protocol PB (phlebotomy), in which 500 ml of venous blood were withdrawn; 3) protocol CO, in which carboxyhemoglobin was maintained at 10% by controlled carbon monoxide inhalation; and 4) protocol C as a control. Both hypoxic sensitivity and ventilation in the absence of hypoxia increased significantly after protocol IH ( P < 0.001 and P < 0.005, respectively, ANOVA) but not after the other three protocols. This indicates that it is the reduction in arterial Po 2 that is primarily important in generating the increase in the acute hypoxic ventilatory response in prolonged hypoxia. The associated reduction in arterial oxygen content is unlikely to play an important role.

Control of breathing in Sherpas at low and high altitude

1980 ◽  
Vol 49 (3) ◽  
pp. 374-379 ◽  
Author(s):  
P. H. Hackett ◽  
J. T. Reeves ◽  
C. D. Reeves ◽  
R. F. Grover ◽  
D. Rennie
Keyword(s):  
High Altitude ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Arterial Oxygen Saturation ◽  
Carbon Dioxide Tension ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Oxygen Administration ◽  
End Tidal

Sherpas are well known for their physical performance at extreme altitudes, yet they are reported to have blunted ventilatory responses to acute hypoxia and relative hypoventilation in chronic hypoxia. To examine this paradox, we studied ventilatory control in Sherpas in comparison to that in Westerners at both low and high altitude. At low altitude, 25 Sherpas had higher minute ventilation, higher respiratory frequency, and lower end-tidal carbon dioxide tension than 25 Westerners. The hypoxic ventilatory response of Sherpas was found to be similar to that in Westerners, even though long altitude exposure had blunted the responses of some Sherpas. At high altitude, Sherpas again had higher minute ventilation and a tendency toward higher arterial oxygen saturation than Westerners. Oxygen administration increased ventilation further in Sherpas but decreased ventilation in Westerners. We conclude that Sherpas differ from other high-altitude natives; their hypoxic ventilatory response is not blunted, and they exhibit relative hyperventilation.

The Ventilatory Response to CO2 after Administration of Frusemide in Normal Man

1972 ◽  
Vol 43 (1) ◽  
pp. 47-54 ◽  
Author(s):  
H. W. Iff ◽  
D. C. Flenley
Keyword(s):  
Ventilatory Response ◽  
Normal Subjects ◽  
Oxygen Balance ◽  
Co2 Response ◽  
Small Shift ◽  
Normal Man ◽  
Slight Rise ◽  
End Tidal ◽  
The Right ◽  
Ventilatory Response To Co2

1. We have determined the ventilatory response to CO2 inhaled in 30% oxygen (balance nitrogen) in eight normal subjects (1) before and during 4 days of 80 mg of oral frusemide daily and (2) within 55–75 min of 80 mg of frusemide orally. 2. Over 4 days the drug decreased serum potassium concentrations, but increased end tidal (and arterial) Pco2 and serum bicarbonate, thus inducing a mild metabolic alkalosis with an appropriate but small shift in CO2 response to the right without a significant change in the slope of the response. The CO2 response was unaltered by oral frusemide 55–75 min earlier. 3. This slight rise in Pco2 during 4 days of frusemide therapy contrasts with the absence of rise in Pco2 after treatment with thiazide diuretics, as reported by others. 4. We discuss possible implications of these results for the selection of an appropriate diuretic in patients with CO2 retention at various phases of their illness.

Augmented hypoxic ventilatory response in men at altitude

1992 ◽  
Vol 73 (1) ◽  
pp. 101-107 ◽  
Author(s):  
M. Sato ◽  
J. W. Severinghaus ◽  
F. L. Powell ◽  
F. D. Xu ◽  
M. J. Spellman
Keyword(s):  
Sea Level ◽  
Ventilatory Response ◽  
Hypoxic Ventilatory Response ◽  
Co2 Response ◽  
Altitude Exposure ◽  
Arterial Ph ◽  
Ventilatory Drive ◽  
Normal Males ◽  
End Tidal ◽  
Arterial O2 Saturation

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1–5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P′CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P′CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4–7). HVR was independent of test SaO2 (range 60–90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)

Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness

1986 ◽  
Vol 60 (4) ◽  
pp. 1407-1412 ◽  
Author(s):  
L. G. Moore ◽  
G. L. Harrison ◽  
R. E. McCullough ◽  
R. G. McCullough ◽  
A. J. Micco ◽  
...  
Keyword(s):  
High Altitude ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Hypoxic Ventilatory Response ◽  
Hypoxic Response ◽  
Altitude Sickness ◽  
Altitude Exposure ◽  
End Tidal ◽  
Arterial O2 Saturation ◽  
Asymptomatic Subjects

Persons with acute altitude sickness hypoventilate at high altitude compared with persons without symptoms. We hypothesized that their hypoventilation was due to low initial hypoxic ventilatory responsiveness, combined with subsequent blunting of ventilation by hypocapnia and/or prolonged hypoxia. To test this hypothesis, we compared eight subjects with histories of acute altitude sickness with four subjects who had been asymptomatic during prior altitude exposure. At a simulated altitude of 4,800 m, the eight susceptible subjects developed symptoms of altitude sickness and had lower minute ventilations and higher end-tidal PCO2′s than the four asymptomatic subjects. In measurements made prior to altitude exposure, ventilatory responsiveness to acute hypoxia was reduced in symptomatic compared to asymptomatic subjects, both when measured under isocapnic and poikolocapnic (no added CO2) conditions. Diminution of the poikilocapnic relative to the isocapnic hypoxic response was similar in the two groups. Ventilation fell, and end-tidal PCO2 rose in both groups during 30 min of steady-state hypoxia relative to values observed acutely. After 4.5 h at 4,800 m, ventilation was lower than values observed acutely at the same arterial O2 saturation. The reduction in ventilation in relation to the hypoxemia present was greater in symptomatic than in asymptomatic persons. Thus the hypoventilation in symptomatic compared to asymptomatic subjects was attributable both to a lower acute hypoxic response and a subsequent greater blunting of ventilation at high altitude.

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.

Time course of augmentation and depression of hypoxic ventilatory responses at altitude

1994 ◽  
Vol 77 (1) ◽  
pp. 313-316 ◽  
Author(s):  
M. Sato ◽  
J. W. Severinghaus ◽  
P. Bickler
Keyword(s):  
Pulse Oximetry ◽  
Sea Level ◽  
Time Course ◽  
Ventilatory Response ◽  
Barometric Pressure ◽  
Hypoxic Ventilatory Response ◽  
Set Point ◽  
Ventilatory Responses ◽  
End Tidal ◽  
Arterial O2 Saturation

Hypoxic ventilatory response (HVR) and hypoxic ventilatory depression (HVD) were measured in six subjects before, during, and after 12 days at 3,810-m altitude (barometric pressure approximately 488 Torr) with and without 15 min of preoxygenation. HVR was tested by 5-min isocapnic steps to 75% arterial O2 saturation measured by pulse oximetry (Spo2) at an isocapnic PCO2 (P*CO2) chosen to set hyperoxic resting ventilation to 140 ml.kg-1.min-1. Hypercapnic ventilatory response (HCVR, 1.min-1.Torr-1) was tested at ambient and high SPO2 6–8 min after a 6- to 10-Torr step increase of end-tidal PCO2 (PETCO2) above P*CO2. HCVR was independent of preoxygenation and was not significantly increased at altitude (when corrected to delta logPCO2). Preoxygenated HVR rose from -1.13 +/- 0.23 (SE) l.min-1.%SPO2(-1) at sea level to -2.17 +/- 0.13 by altitude day 12, without reaching a plateau, and returned to control after return to sea level for 4 days. Ambient HVR was measured at P*CO2 by step reduction of SPO2 from its ambient value (86–91%) to approximately 75%. Ambient HVR slope was not significantly less, but ventilation at equal levels of SPO2 and PCO2 was lower by 13.3 +/- 2.4 l/min on day 2 (SPO2 = 86.2 +/- 2.3) and by 5.9 +/- 3.5 l/min on day 12 (SPO2 = 91.0 +/- 1.5; P < 0.05). This lower ventilation was estimated (from HCVR) to be equivalent to an elevation of the central chemoreceptor PCO2 set point of 9.2 +/- 2.1 Torr on day 2 and 4.5 +/- 1.3 on day 12.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of Airway Anaesthesia on the Control of Breathing and the Sensation of Breathlessness in Man

1985 ◽  
Vol 68 (2) ◽  
pp. 215-225 ◽  
Author(s):  
A. J. Winning ◽  
R. D. Hamilton ◽  
S. A. Shea ◽  
C. Knott ◽  
A. Guz
Keyword(s):  
Tidal Volume ◽  
Ventilatory Response ◽  
Normal Subjects ◽  
Cough Reflex ◽  
Before And After ◽  
Median Diameter ◽  
Receptor Block ◽  
Normal Man ◽  
End Tidal ◽  
Ventilatory Response To Co2

1. The effect on ventilation of airway anaesthesia, produced by the inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter = 4.77 μm), was studied in 12 normal subjects. 2. The dose and distribution of the aerosol were determined from lung scans after the addition to bupivacaine of 99mTc. Bupivacaine labelled in this way was deposited primarily in the central airways. The effectiveness and duration of airway anaesthesia were assessed by the absence of the cough reflex to the inhalation of three breaths of a 5% citric acid aerosol. Airway anaesthesia always lasted more than 20 min. 3. Resting ventilation was measured, by respiratory inductance plethysmography, before and after inhalation of saline and bupivacaine aerosols. The ventilatory response to maximal incremental exercise and, separately, to CO2 inhalation was studied after the inhalation of saline and bupivacaine aerosols. Breathlessness was quantified by using a visual analogue scale (VAS) during a study and by questioning on its completion. 4. At rest, airway anaesthesia had no effect on mean tidal volume (VT), inspiratory time (Ti), expiratory time (Te) or end-tidal Pco2, although the variability of tidal volume was increased. On exercise, slower deeper breathing was produced and breathlessness was reduced. The ventilatory response to CO2 was increased. 5. The results suggest that stretch receptors in the airways modulate the pattern of breathing in normal man when ventilation is stimulated by exercise; their activation may also be involved in the genesis of the associated breathlessness. 6. A hypothesis in terms of a differential airway/alveolar receptor block, is proposed to explain the exaggerated ventilatory response to CO2.

Calcium/calmodulin-dependent kinase II mediates critical components of the hypoxic ventilatory response within the nucleus of the solitary tract in adult rats

2005 ◽  
Vol 289 (3) ◽  
pp. R871-R876 ◽  
Author(s):  
Stephen R. Reeves ◽  
Edwin S. Carter ◽  
Shang Z. Guo ◽  
David Gozal
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Respiratory Frequency ◽  
Whole Body ◽  
Solitary Tract ◽  
Hypoxic Ventilatory Response ◽  
Adult Rats ◽  
Osmotic Pumps ◽  
Calcium Calmodulin Dependent

Calcium/calmodulin-dependent kinase II (CaMKII) is an ubiquitous second messenger that is highly expressed in neurons, where it has been implicated in some of the pathways regulating neuronal discharge as well as N-methyl-d-aspartate receptor-mediated synaptic plasticity. The full expression of the mammalian hypoxic ventilatory response (HVR) requires intact central relays within the nucleus of the solitary tract (NTS), and neural transmission of hypoxic afferent input is mediated by glutamatergic receptor activity, primarily through N-methyl-d-aspartate receptors. To examine the functional role of CaMKII in HVR, KN-93, a highly selective antagonist of CaMKII, was microinjected in the NTS via bilaterally placed osmotic pumps in freely behaving adult male Sprague-Dawley rats for 3 days. Vehicle-loaded osmotic pumps were surgically placed in control animals, and adequate placement of cannulas was ascertained for all animals. HVR was measured using whole body plethysmography during exposure to 10% O2-balance N2 for 20 min. Compared with control rats, KN-93 administration elicited marked attenuations of peak HVR (pHVR) but did not modify normoxic minute ventilation. Differences in pHVR were primarily attributable to diminished respiratory frequency recruitments during pHVR without significant differences in tidal volume. These findings indicate that CaMKII activation in the NTS mediates respiratory frequency components of the ventilatory response to acute hypoxia; however, CaMKII activity does not appear to underlie components of normoxic ventilation.

The Ventilatory Effects of Doxapram in Normal Man

1983 ◽  
Vol 65 (1) ◽  
pp. 65-69 ◽  
Author(s):  
P. M. A. Calverley ◽  
R. H. Robson ◽  
P. K. Wraith ◽  
L. F. Prescott ◽  
D. C. Flenley
Keyword(s):  
Oxygen Uptake ◽  
Ventilatory Response ◽  
Co2 Production ◽  
Central Action ◽  
Ventilatory Responses ◽  
Ventilatory Effects ◽  
Normal Man ◽  
End Tidal ◽  
End Tidal Co2 ◽  
Ventilatory Response To Co2

1. To determine the mode of action of doxapram in man we have measured ventilation, oxygen uptake, CO2 production, hypoxic and hypercapnic ventilatory responses in six healthy men before and during intravenous infusion to maintain a constant plasma level. 2. Doxapram changed neither resting oxygen uptake nor CO2 production but produced a substantial increase in resting ventilation at both levels of end-tidal CO2 studied. 3. Doxapram increased the ventilatory response to isocapnic hypoxia from − 0.8 ± 0.4 litre min−1 (%Sao2)−1 to −1.63 ± 0.9 litres min−1 (%Sao2)−1. This was similar to the increase in hypoxic sensitivity which resulted from raising the end-tidal CO2 by 0.5 kPa without adding doxapram. 4. The slope of the ventilatory response to rebreathing CO2 rose from 11.6 ± 5.3 litres min−1 kPa−1 to 20,4 ± 9.8 litres min−1 kPa−1 during doxapram infusion. 5. The marked increase in the ventilatory response to CO2 implies that doxapram has a central action, but the potentiation of the hypoxic drive also suggests that the drug acts on peripheral chemoreceptors, or upon their central connections, at therapeutic concentrations in normal unanaesthetized subjects.

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