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Integration of Respiratory Responses to Changes in Alveolar Partial Pressures of CO2 and O2 and in Arterial pH

D. J. C. Cunningham, P. A. Robbins, C. B. Wolff

10.1002/cphy.cp030215

Source: Supplement 11: Handbook of Physiology, The Respiratory System, Control of Breathing

Originally published: 1986

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Feedback Loop
1.1 Metabolic Hyperbola
1.2 Steady‐State Relations Between Stimulus and Response
1.3 Sites of Interaction Between Hypercapnic and Hypoxic Drives
1.4 Apnea Point: Carbon Dioxide‐Acid Thresholds
2 Dynamic Properties of Respiratory Control System
2.1 Dynamics of Receptors
2.2 Dynamic Properties of Overall System
2.3 Respiratory Oscillations and Whole‐System Responses
3 Pattern of Breathing
3.1 Mean Values in Steady States
3.2 Changing States: Dynamic Responses
3.3 Nonclassic Dynamic Stimuli
4 Potassium
5 Stability of Alveolar and Arterial CO2 and O2 Tensions
6 Concluding Remarks
Figure 1. Figure 1.

Two classes of respiratory stimuli. Feedforward: any or all of these factors may contribute to the prediction of the ventilation () required. Their actions are not necessarily additive nor are they mutually exclusive. Feedback: these factors tell the system how well it is actually performing. They have no predictive properties. When feedforward prediction is correct, feedback signal is ∼0.
Figure 2. Figure 2.

Relations between and and between and at two rates of and . A and B: metabolic hyperbolas; i.e., the effects of changing on and at two rates of and . Dashed horizontal lines are asymptotes when partial pressure of inspiratory gas is other than 0. In this figure, is the independent variable. C and D: controller relationships; i.e., effects of and on . Axes represent same variables as in A and B but are reversed to emphasize that partial pressures of alveolar gases are now the independent variables. These are controller relations. In C, hypoxia line is derived from Nielsen and Smith 339. In D, upper line is a hypercapnicisocapnic line after Cormack et al. 79; dotted line represents true asphyxia, i.e., rebreathing air (cf. Fig. 3, top trace). E and F: controller relationships of C and D superimposed on metabolic hyperbolas of A and B. Circles denote intersections of metabolic hyperbolas with appropriate controller relations: they are the points that uniquely satisfy both relations. Note steepness of CO2 controller line and shallowness of “aviators'” hypoxia line. In F, upper line is isocapnic hypoxic response line determined by Weil et al. 427 in mild exercise. It curves upward more steeply than “aviators'” line and is not quite an appropriate representation of the contribution of hypoxia to the controller system during exercise, but is the best available for the purpose.
Figure 3. Figure 3.

Rebreathing from a 6‐liter Krogh spirometer. Values beside traces are compositions of gas remaining in spirometer at ends of runs. A: spirometer initially filled with air; no CO2 absorber in circuit; asphyxial changes in gas composition. B: spirometer filled with air; CO2 absorber in circuit; progressive hypoxia with developing hypocapnia. C: spirometer filled with O2; no CO2 absorber in circuit; progressive hypercapnia without hypoxia. Note that 1) hypoxia with hypocapnia failed to stimulate breathing until experiment was well advanced and 2) from quite early in runs A and C, asphyxia stimulated progressively more than hypercapnia alone.

From Douglas and Priestley 132
Figure 4. Figure 4.

Ventilation () vs. and pHa at rest in physiologically neutral (o) and chronic metabolic acidemic (•) states. Numbers beside points are pHa in A and in B. Dashed arrows indicate pairs of points of equal pHa or and allow derivation of partial effects of ΔpHa and Δ (coefficients a and b of Eq. 6). C: unitary hypothesis; is shown as unique function of pH in vicinity of hypothetical receptors, which are more or less remote from blood. This sort of argument has been used in relation to intracranial chemosensitivity (e.g., ref. 348).

From Cunningham 92; based on data from Nielsen 338 and Gray 199
Figure 5. Figure 5.

Steady‐state effect of changing on : controller relation. From normal upward, : relation at a single is linear. At and below normal extrapolations of these lines downward converge to meet not far from horizontal axis; lowering increases slope (S) with little effect on intercept B. Relation between S and is described in Eqs. 7 and 8. Raising decreases S and shifts horizontal intercept leftward (B → B′) as discussed in Hyperoxia, hypoxia, and “central depression,” p. 484. As a result of this dual effect, hyperoxic and euoxic lines cross at = 25–35 liters/min: hyperoxia appears to stimulate below the crossing point but to depress above it. At or below normal linearity breaks down and lines become nearly flat. Region labeled “zone of uncertainty” is discussed in relation to Fig. 13.

Adapted from Lambertsen et al. 270 and Cunningham et al. 108
Figure 6. Figure 6.

Scheme for considering interactions between feedback stimuli. More complex versions might include feedback links from Ic (input from central chemosensitive tissue) to Ip (input from peripheral chemoreceptors) or from Ig (output from brain stem pattern generator) to Ip, and a second central CO2‐H+ component, one available for multiplicative interaction with peripheral drive and the other not (see steady‐state studies, p. 487, dynamic studies, p. 488, and studies with physical separation of drives, p. 489).

Adapted from van Beek 31
Figure 7. Figure 7.

Peripheral (A) or central (B) multiplicative interaction. ‐H+ and Drhypox, drive from CO2‐H+ complex and hypoxia, respectively; superscripts p and c, peripheral and central influences, respectively.
Figure 8. Figure 8.

Carotid body afferent fibers in cat. Schematic representation of frequencies of discharge (drawn as if in single fibers) as functions of (left) and (right). Increasing CO2‐H+ increases responsiveness to hypoxia, and increasing hypoxia increases responsiveness to rise of . Note that hyperoxia depresses but does not extinguish the response to CO2. CO2 thresholds based on data in Fig. 10. Curves represent consensus from many authors.
Figure 9. Figure 9.

A. Artificial brain perfusion. Ventilation () as functions of peripheral () at several levels of constant peripheral (); central () was held constant. Measurements occupied 2 h. Regression lines are shown; Sp and K1 are parameters in Eq. 19. Note tendency for lines to flatten when > 2 liters/min.

Adapted from van Beek et al. 32.] B. Artificial brain perfusion. Ventilation () as functions of peripheral () at three levels of central (); and are constant. Note central hypercapnia displaces response line upward (expressed as increase of K1 of Eq. 19 but does not change its slope. [Adapted from van Beek et al. 32.] C. Artificial brain perfusion. i: as functions of central () during constant peripheral hypercapnia and at constant central (). Open symbols, peripheral () high; closed symbols, peripheral () low. Note that peripheral stimulation displaced central CO2 response line upward without appreciable change of S and that there was no flattening of lower end of response line even in deep hypocapnia (i.e., no “dogleg,” see hypocapnic range in conscious humans, p. 496). Breathing became irregular at lowest . [Adapted from Berkenbosch et al. 36.] ii: as functions of . Lowering displaced response line downward without change of S. [Adapted from van Beek 31.] iii: Diagram of factors influencing central response line. Constant peripheral stimulation of either kind displaced line upward. Central hypoxia displaced line downward: in Eq. 22, decreases in increased K, whereas Sc was independent of gaseous stimuli. D. Artificial brain perfusion. Ventilation () as function of peripheral (). Fitted curves: solid line, exponential function; dotted line, hyperbolic function. Horizontal line is reference value at euoxic , and double arrow shows effect of hyperoxia. [From van Beek 31.] E. Artificial brain perfusion. Ventilation () as function of central (). Lines and double arrow as in Fig. 9D. [From van Beek 31.] F. Brain not separately perfused. Change of from euoxic value as function of at fixed (gas pressures the same in central and peripheral arterial blood). Lines and double arrow as in Fig. 9D. From van Beek 31
Figure 10. Figure 10.

Anesthetized cat. Relations between and at threshold for carotid chemoreceptor response and at first inspiration after postoverventilation apnea.

From Lahiri et al. 267
Figure 11. Figure 11.

Artificial brain perfusion. Peripheral () at which apnea occurred as function of central (). Line with its 95% confidence limits (dotted lines) was calculated from separate determinations of parameters Sp, Sc, and K of Eq. 22 on same cat; its slope is Sc/Sp.

From de Goede et al. 448
Figure 12. Figure 12.

A: ventilation () as function of at steady of 37 (•), 47 (+), 110 (○), and 169 (×) Torr. Note: above and to right, response was linear and hypoxia affected mainly the slopes of lines. Below sharp inflection, was largely independent of (“dogleg”).

From Nielsen and Smith 339.] B: quasi‐steady‐state plot of against of normal subject. started at 36 Torr for 15 min (giving ∼ 47 Torr). was lowered by 2 Torr every 3rd min and was adjusted to hold as near as possible to 47 Torr; points are mean and over approximately each minute. Over an upper range, and fell linearly; over a lower range, was nearly constant with falling steadily, but the slope here was much less than over upper range. Inset: enlargement of zone of instability. Here, while continued to be lowered at regular intervals, remained at about the same value; i.e., ‐ difference increased. From Young 443
Figure 13. Figure 13.

Relations between steady‐state metabolic hyperbola for resting subjects and reported nonlinearities of euoxic CO2 controller lines with their doglegs.
Figure 14. Figure 14.

Diagram of time‐dependent responses of carotid chemoreceptor afferent units to up and down steps of stimulation. Overshoot of response to change of , if it exists at all, is much less than that to change of . The latter shows a deep trough at “off,” which may be more or less truncated by frequency reaching zero. This could give rise to overall asymmetry and rectification in response to repetitive alternate ups and downs. (Based on drawing by R. W. Torrance representing a consensus from several authors.)
Figure 15. Figure 15.

Ventilatory responses to step changes of inspiratory CO2, 0% → 5.3% → 0%, at vertical arrows. Alveolar CO2 shows overshoot, which was more pronounced after downstep.

From Padget 347
Figure 16. Figure 16.

Manipulation of to give steplike changes of . was simultaneously manipulated to hold constant (top trace) in face of changing ventilation.

From Swanson and Bellville 409
Figure 17. Figure 17.

Arterial pH oscillations in humans at transition from rest to exercise. From top to bottom: arterial pH; inspiratory Vt; at mouth. Slopes of pH downstrokes are proportional to slopes of preceding expiratory alveolar plateaus.

From Band et al. 23, reprinted by permission from Nature London 283: 84–85, © 1980 Macmillan Journals Limited
Figure 18. Figure 18.

Time dependence of reflex response to brief stimulation of carotid body with boluses of CO2‐equilibrated saline at times indicated by dashes on Vt traces. In traces 4 to 9, current inspiration was stimulated; in the other traces there was no effect. Lengthening of expiration can be seen in traces 1, 2, 11, and 12 but is more obvious in Nye et al. 340.

Adapted from Black and Torrance 47
Figure 19. Figure 19.

Lung‐to‐ear circulation time during mild‐to‐moderate exercise in one air‐breathing subject plotted against respiratory period: linear correlation coefficient, 0.89. Circulation time was not significantly correlated with either Vt or mean inspiratory flow.

Adapted from Coulter et al. 81
Figure 20. Figure 20.

Two of 3 relations between Vt and Tt. 1: Cigar‐shaped clusters around their means (•) show distributions of individual breaths under steady respiratory drive 371; their long axes point toward origin indicating that, at each level, Vt/Tt (i.e., single‐breath ventilation) is relatively constant in face of breath‐by‐breath scatter of Vt and Tt. With greater mean (resulting from increased drive), cigar‐shaped clusters slope more steeply around shorter Tt and larger Vt. 2: Curve describing mean steady‐state values (solid line) below break point is (Vt ‐ k) (Tt − 60/m) = constant = 60k/ m. This reduces to Eq. 24 224. Mean steady‐state relation is largely independent of the nature of the drive in awake humans. Third relation (not illustrated here) is observed during transitions between steady states (e.g., during rebreathing, step changes, etc.) and is illustrated in Fig. 24.
Figure 21. Figure 21.

Steady‐state pattern of breathing in conscious humans. Vt‐Ti‐Te relations incorporating variation of Te below breakpoint; Te is plotted leftward from origin following usage of Kay et al. 248]. See Fig. 20 for explanation of • and cigar‐shaped clusters. Breath‐by‐breath scatter occurs in both inspiratory and expiratory variables. In range 1, with increasing , nearly all shortening of Tt (Fig. 20) is due to shortening of Te. In range 2, increasing Vt is associated with shortening of both Ti and Te. Below breakpoint, therefore, Ti is correlated with Te only on the basis of individual breaths; means are not correlated. Above breakpoint, means of Ti and Te are also correlated. In anesthetized cats, “range 2” pattern is usually seen over the whole range of Vt. In unanesthetized cats, pattern is qualitatively like the human one 183.

Adapted from Clark and Euler 71 and Gardner 178
Figure 22. Figure 22.

Effects of partial and complete vagal blockade on pattern of breathing in anesthetized rabbits. Blockade of pulmonary stretch afferents by SO2 inhalation A: data from Davies et al. 114] and cooling to 8°C [B: data from Kiwull‐Schoene et al. 255] (control, C). Complete vagal blockade by vagotomy (A) and cooling vagi to 0°C (B). In both cases, upper high‐ventilation points were obtained by CO2 inhalation.

Reprinted by permission of the publisher from the chapter by Petersen in Modelling and Control of Breathing, p. 248–257. © 1983 by Elsevier Science Publishing Co., Inc
Figure 23. Figure 23.

Top: scatter in Vt, Ti, and Te in steady states of CO2 inhalation with (•) and without (○) hypoxia in normal subject at rest. Fitted relation (not shown) had breakpoint at Vt ∼1.5 liters. There was an unusually large amount of scatter, especially above breakpoint. Bottom: same Te data replotted after subtracting (0.7 × Ti) from each point. Coefficient 0.7 was obtained as described by Cunningham and Gardner 99. Scatter was substantially reduced, showing that most of it in Te was linked to scatter in Ti. Furthermore there was now no obvious breakpoint, suggesting that this, too, was primarily an inspiratory phenomenon.

From Gardner 178
Figure 24. Figure 24.

Relations between Vt and Te and between Vt and Ti during transitions between steady states (+). Top: isocapnic steps of between 85 and 50 Torr. Bottom: hyperoxic steps of (5–7 Torr). Seven to 12 runs of each kind averaged. •, Upward steps of drive; ○, downward steps of drive. Note different pathways followed with the two kinds of step.

From Gardner 179
Figure 25. Figure 25.

Average of 8 responses to intravenous injection of 0.045 mmol KCl in anesthetized cat. Ventilation shown as mean values ± 1 SD. Time zero is time at which [K+]a (measured with electrode positioned in abdominal aorta) started to rise. For the 8 injections, mean [K+]a was calculated at 0.2‐s intervals and line was drawn through these points. Mean discharge rate (impulses/s) recorded from chemoreceptor fiber was calculated at 0.2‐s intervals. •, Three‐point running average of these means.

From Linton and Band 287
Figure 26. Figure 26.

Cumulative plot (from papers of C. G. Douglas) of relationships between , and ambient barometric pressure (Pb) and between , and Pb in normal men acclimatized to a wide range of high altitudes. Data from FitzGerald (•; refs. 162,163) are supplemented by various U.S. expeditions to the Chilean Andes (x; ref. 123) and to Mount Everest [*; ref. 202 (G), 423 (W)] and by data from Rahn and Otis (Δ; ref. 374) and Houston and Riley (+; ref. 234). FitzGerald's , was calculated from measured , and an assumed R of 0.83. Houston and Riley's values were for men not fully acclimatized and were obtained in a chamber. Height (axis on right of figure) equivalent to Pb is found from curved line. Striking linearity of relations between gas tensions and Pb can be seen, at least from sea‐level pressure to approximately half this value.

Adapted from Cunningham and Drysdale 95
Figure 27. Figure 27.

Each point represents and in a single patient with chronic asthma, stable for at least 1 wk. Least squares regression line ( = 0.23 + 16.6 mmHg) was not significantly different from that derived as likely from data of Fig. 26 ( = 0.269 + 14.3 mmHg) assuming alveolar‐arterial gradient for of 7 mmHg 437. This group of patients with intermittent obstructive airway disease seemed most likely to acclimatize normally because 4 such patients had been found to have virtually normal respiratory oscillations. They seem to adjust their eupneic to essentially the same value as would be expected from their had they been altitude dwellers. See ref. 73 for patients' details.

From Cochrane et al. 73


Figure 1.

Two classes of respiratory stimuli. Feedforward: any or all of these factors may contribute to the prediction of the ventilation () required. Their actions are not necessarily additive nor are they mutually exclusive. Feedback: these factors tell the system how well it is actually performing. They have no predictive properties. When feedforward prediction is correct, feedback signal is ∼0.



Figure 2.

Relations between and and between and at two rates of and . A and B: metabolic hyperbolas; i.e., the effects of changing on and at two rates of and . Dashed horizontal lines are asymptotes when partial pressure of inspiratory gas is other than 0. In this figure, is the independent variable. C and D: controller relationships; i.e., effects of and on . Axes represent same variables as in A and B but are reversed to emphasize that partial pressures of alveolar gases are now the independent variables. These are controller relations. In C, hypoxia line is derived from Nielsen and Smith 339. In D, upper line is a hypercapnicisocapnic line after Cormack et al. 79; dotted line represents true asphyxia, i.e., rebreathing air (cf. Fig. 3, top trace). E and F: controller relationships of C and D superimposed on metabolic hyperbolas of A and B. Circles denote intersections of metabolic hyperbolas with appropriate controller relations: they are the points that uniquely satisfy both relations. Note steepness of CO2 controller line and shallowness of “aviators'” hypoxia line. In F, upper line is isocapnic hypoxic response line determined by Weil et al. 427 in mild exercise. It curves upward more steeply than “aviators'” line and is not quite an appropriate representation of the contribution of hypoxia to the controller system during exercise, but is the best available for the purpose.



Figure 3.

Rebreathing from a 6‐liter Krogh spirometer. Values beside traces are compositions of gas remaining in spirometer at ends of runs. A: spirometer initially filled with air; no CO2 absorber in circuit; asphyxial changes in gas composition. B: spirometer filled with air; CO2 absorber in circuit; progressive hypoxia with developing hypocapnia. C: spirometer filled with O2; no CO2 absorber in circuit; progressive hypercapnia without hypoxia. Note that 1) hypoxia with hypocapnia failed to stimulate breathing until experiment was well advanced and 2) from quite early in runs A and C, asphyxia stimulated progressively more than hypercapnia alone.

From Douglas and Priestley 132


Figure 4.

Ventilation () vs. and pHa at rest in physiologically neutral (o) and chronic metabolic acidemic (•) states. Numbers beside points are pHa in A and in B. Dashed arrows indicate pairs of points of equal pHa or and allow derivation of partial effects of ΔpHa and Δ (coefficients a and b of Eq. 6). C: unitary hypothesis; is shown as unique function of pH in vicinity of hypothetical receptors, which are more or less remote from blood. This sort of argument has been used in relation to intracranial chemosensitivity (e.g., ref. 348).

From Cunningham 92; based on data from Nielsen 338 and Gray 199


Figure 5.

Steady‐state effect of changing on : controller relation. From normal upward, : relation at a single is linear. At and below normal extrapolations of these lines downward converge to meet not far from horizontal axis; lowering increases slope (S) with little effect on intercept B. Relation between S and is described in Eqs. 7 and 8. Raising decreases S and shifts horizontal intercept leftward (B → B′) as discussed in Hyperoxia, hypoxia, and “central depression,” p. 484. As a result of this dual effect, hyperoxic and euoxic lines cross at = 25–35 liters/min: hyperoxia appears to stimulate below the crossing point but to depress above it. At or below normal linearity breaks down and lines become nearly flat. Region labeled “zone of uncertainty” is discussed in relation to Fig. 13.

Adapted from Lambertsen et al. 270 and Cunningham et al. 108


Figure 6.

Scheme for considering interactions between feedback stimuli. More complex versions might include feedback links from Ic (input from central chemosensitive tissue) to Ip (input from peripheral chemoreceptors) or from Ig (output from brain stem pattern generator) to Ip, and a second central CO2‐H+ component, one available for multiplicative interaction with peripheral drive and the other not (see steady‐state studies, p. 487, dynamic studies, p. 488, and studies with physical separation of drives, p. 489).

Adapted from van Beek 31


Figure 7.

Peripheral (A) or central (B) multiplicative interaction. ‐H+ and Drhypox, drive from CO2‐H+ complex and hypoxia, respectively; superscripts p and c, peripheral and central influences, respectively.



Figure 8.

Carotid body afferent fibers in cat. Schematic representation of frequencies of discharge (drawn as if in single fibers) as functions of (left) and (right). Increasing CO2‐H+ increases responsiveness to hypoxia, and increasing hypoxia increases responsiveness to rise of . Note that hyperoxia depresses but does not extinguish the response to CO2. CO2 thresholds based on data in Fig. 10. Curves represent consensus from many authors.



Figure 9.

A. Artificial brain perfusion. Ventilation () as functions of peripheral () at several levels of constant peripheral (); central () was held constant. Measurements occupied 2 h. Regression lines are shown; Sp and K1 are parameters in Eq. 19. Note tendency for lines to flatten when > 2 liters/min.

Adapted from van Beek et al. 32.] B. Artificial brain perfusion. Ventilation () as functions of peripheral () at three levels of central (); and are constant. Note central hypercapnia displaces response line upward (expressed as increase of K1 of Eq. 19 but does not change its slope. [Adapted from van Beek et al. 32.] C. Artificial brain perfusion. i: as functions of central () during constant peripheral hypercapnia and at constant central (). Open symbols, peripheral () high; closed symbols, peripheral () low. Note that peripheral stimulation displaced central CO2 response line upward without appreciable change of S and that there was no flattening of lower end of response line even in deep hypocapnia (i.e., no “dogleg,” see hypocapnic range in conscious humans, p. 496). Breathing became irregular at lowest . [Adapted from Berkenbosch et al. 36.] ii: as functions of . Lowering displaced response line downward without change of S. [Adapted from van Beek 31.] iii: Diagram of factors influencing central response line. Constant peripheral stimulation of either kind displaced line upward. Central hypoxia displaced line downward: in Eq. 22, decreases in increased K, whereas Sc was independent of gaseous stimuli. D. Artificial brain perfusion. Ventilation () as function of peripheral (). Fitted curves: solid line, exponential function; dotted line, hyperbolic function. Horizontal line is reference value at euoxic , and double arrow shows effect of hyperoxia. [From van Beek 31.] E. Artificial brain perfusion. Ventilation () as function of central (). Lines and double arrow as in Fig. 9D. [From van Beek 31.] F. Brain not separately perfused. Change of from euoxic value as function of at fixed (gas pressures the same in central and peripheral arterial blood). Lines and double arrow as in Fig. 9D. From van Beek 31


Figure 10.

Anesthetized cat. Relations between and at threshold for carotid chemoreceptor response and at first inspiration after postoverventilation apnea.

From Lahiri et al. 267


Figure 11.

Artificial brain perfusion. Peripheral () at which apnea occurred as function of central (). Line with its 95% confidence limits (dotted lines) was calculated from separate determinations of parameters Sp, Sc, and K of Eq. 22 on same cat; its slope is Sc/Sp.

From de Goede et al. 448


Figure 12.

A: ventilation () as function of at steady of 37 (•), 47 (+), 110 (○), and 169 (×) Torr. Note: above and to right, response was linear and hypoxia affected mainly the slopes of lines. Below sharp inflection, was largely independent of (“dogleg”).

From Nielsen and Smith 339.] B: quasi‐steady‐state plot of against of normal subject. started at 36 Torr for 15 min (giving ∼ 47 Torr). was lowered by 2 Torr every 3rd min and was adjusted to hold as near as possible to 47 Torr; points are mean and over approximately each minute. Over an upper range, and fell linearly; over a lower range, was nearly constant with falling steadily, but the slope here was much less than over upper range. Inset: enlargement of zone of instability. Here, while continued to be lowered at regular intervals, remained at about the same value; i.e., ‐ difference increased. From Young 443


Figure 13.

Relations between steady‐state metabolic hyperbola for resting subjects and reported nonlinearities of euoxic CO2 controller lines with their doglegs.



Figure 14.

Diagram of time‐dependent responses of carotid chemoreceptor afferent units to up and down steps of stimulation. Overshoot of response to change of , if it exists at all, is much less than that to change of . The latter shows a deep trough at “off,” which may be more or less truncated by frequency reaching zero. This could give rise to overall asymmetry and rectification in response to repetitive alternate ups and downs. (Based on drawing by R. W. Torrance representing a consensus from several authors.)



Figure 15.

Ventilatory responses to step changes of inspiratory CO2, 0% → 5.3% → 0%, at vertical arrows. Alveolar CO2 shows overshoot, which was more pronounced after downstep.

From Padget 347


Figure 16.

Manipulation of to give steplike changes of . was simultaneously manipulated to hold constant (top trace) in face of changing ventilation.

From Swanson and Bellville 409


Figure 17.

Arterial pH oscillations in humans at transition from rest to exercise. From top to bottom: arterial pH; inspiratory Vt; at mouth. Slopes of pH downstrokes are proportional to slopes of preceding expiratory alveolar plateaus.

From Band et al. 23, reprinted by permission from Nature London 283: 84–85, © 1980 Macmillan Journals Limited


Figure 18.

Time dependence of reflex response to brief stimulation of carotid body with boluses of CO2‐equilibrated saline at times indicated by dashes on Vt traces. In traces 4 to 9, current inspiration was stimulated; in the other traces there was no effect. Lengthening of expiration can be seen in traces 1, 2, 11, and 12 but is more obvious in Nye et al. 340.

Adapted from Black and Torrance 47


Figure 19.

Lung‐to‐ear circulation time during mild‐to‐moderate exercise in one air‐breathing subject plotted against respiratory period: linear correlation coefficient, 0.89. Circulation time was not significantly correlated with either Vt or mean inspiratory flow.

Adapted from Coulter et al. 81


Figure 20.

Two of 3 relations between Vt and Tt. 1: Cigar‐shaped clusters around their means (•) show distributions of individual breaths under steady respiratory drive 371; their long axes point toward origin indicating that, at each level, Vt/Tt (i.e., single‐breath ventilation) is relatively constant in face of breath‐by‐breath scatter of Vt and Tt. With greater mean (resulting from increased drive), cigar‐shaped clusters slope more steeply around shorter Tt and larger Vt. 2: Curve describing mean steady‐state values (solid line) below break point is (Vt ‐ k) (Tt − 60/m) = constant = 60k/ m. This reduces to Eq. 24 224. Mean steady‐state relation is largely independent of the nature of the drive in awake humans. Third relation (not illustrated here) is observed during transitions between steady states (e.g., during rebreathing, step changes, etc.) and is illustrated in Fig. 24.



Figure 21.

Steady‐state pattern of breathing in conscious humans. Vt‐Ti‐Te relations incorporating variation of Te below breakpoint; Te is plotted leftward from origin following usage of Kay et al. 248]. See Fig. 20 for explanation of • and cigar‐shaped clusters. Breath‐by‐breath scatter occurs in both inspiratory and expiratory variables. In range 1, with increasing , nearly all shortening of Tt (Fig. 20) is due to shortening of Te. In range 2, increasing Vt is associated with shortening of both Ti and Te. Below breakpoint, therefore, Ti is correlated with Te only on the basis of individual breaths; means are not correlated. Above breakpoint, means of Ti and Te are also correlated. In anesthetized cats, “range 2” pattern is usually seen over the whole range of Vt. In unanesthetized cats, pattern is qualitatively like the human one 183.

Adapted from Clark and Euler 71 and Gardner 178


Figure 22.

Effects of partial and complete vagal blockade on pattern of breathing in anesthetized rabbits. Blockade of pulmonary stretch afferents by SO2 inhalation A: data from Davies et al. 114] and cooling to 8°C [B: data from Kiwull‐Schoene et al. 255] (control, C). Complete vagal blockade by vagotomy (A) and cooling vagi to 0°C (B). In both cases, upper high‐ventilation points were obtained by CO2 inhalation.

Reprinted by permission of the publisher from the chapter by Petersen in Modelling and Control of Breathing, p. 248–257. © 1983 by Elsevier Science Publishing Co., Inc


Figure 23.

Top: scatter in Vt, Ti, and Te in steady states of CO2 inhalation with (•) and without (○) hypoxia in normal subject at rest. Fitted relation (not shown) had breakpoint at Vt ∼1.5 liters. There was an unusually large amount of scatter, especially above breakpoint. Bottom: same Te data replotted after subtracting (0.7 × Ti) from each point. Coefficient 0.7 was obtained as described by Cunningham and Gardner 99. Scatter was substantially reduced, showing that most of it in Te was linked to scatter in Ti. Furthermore there was now no obvious breakpoint, suggesting that this, too, was primarily an inspiratory phenomenon.

From Gardner 178


Figure 24.

Relations between Vt and Te and between Vt and Ti during transitions between steady states (+). Top: isocapnic steps of between 85 and 50 Torr. Bottom: hyperoxic steps of (5–7 Torr). Seven to 12 runs of each kind averaged. •, Upward steps of drive; ○, downward steps of drive. Note different pathways followed with the two kinds of step.

From Gardner 179


Figure 25.

Average of 8 responses to intravenous injection of 0.045 mmol KCl in anesthetized cat. Ventilation shown as mean values ± 1 SD. Time zero is time at which [K+]a (measured with electrode positioned in abdominal aorta) started to rise. For the 8 injections, mean [K+]a was calculated at 0.2‐s intervals and line was drawn through these points. Mean discharge rate (impulses/s) recorded from chemoreceptor fiber was calculated at 0.2‐s intervals. •, Three‐point running average of these means.

From Linton and Band 287


Figure 26.

Cumulative plot (from papers of C. G. Douglas) of relationships between , and ambient barometric pressure (Pb) and between , and Pb in normal men acclimatized to a wide range of high altitudes. Data from FitzGerald (•; refs. 162,163) are supplemented by various U.S. expeditions to the Chilean Andes (x; ref. 123) and to Mount Everest [*; ref. 202 (G), 423 (W)] and by data from Rahn and Otis (Δ; ref. 374) and Houston and Riley (+; ref. 234). FitzGerald's , was calculated from measured , and an assumed R of 0.83. Houston and Riley's values were for men not fully acclimatized and were obtained in a chamber. Height (axis on right of figure) equivalent to Pb is found from curved line. Striking linearity of relations between gas tensions and Pb can be seen, at least from sea‐level pressure to approximately half this value.

Adapted from Cunningham and Drysdale 95


Figure 27.

Each point represents and in a single patient with chronic asthma, stable for at least 1 wk. Least squares regression line ( = 0.23 + 16.6 mmHg) was not significantly different from that derived as likely from data of Fig. 26 ( = 0.269 + 14.3 mmHg) assuming alveolar‐arterial gradient for of 7 mmHg 437. This group of patients with intermittent obstructive airway disease seemed most likely to acclimatize normally because 4 such patients had been found to have virtually normal respiratory oscillations. They seem to adjust their eupneic to essentially the same value as would be expected from their had they been altitude dwellers. See ref. 73 for patients' details.

From Cochrane et al. 73
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Article Title: Integration of Respiratory Responses to Changes in Alveolar Partial Pressures of CO2 and O2 and in Arterial pH
 

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D. J. C. Cunningham, P. A. Robbins, C. B. Wolff. Integration of Respiratory Responses to Changes in Alveolar Partial Pressures of CO2 and O2 and in Arterial pH. Compr Physiol 2011, Supplement 11: Handbook of Physiology, The Respiratory System, Control of Breathing: 475-528. First published in print 1986. doi: 10.1002/cphy.cp030215