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The ventilatory response to lowering potassium with dextrose and insulin in subjects with hyperkalaemia
Respiration Physiology, 76 (1989) 393-398 Elsevier
393
RSP 01541
The ventilatory response to lowering potassium with dextrose and insulin in subjects with hyperkalaemia David J. Paterson ~, Jon. S. Friedland 2, Des. O. Oliver 2 and Peter A. Robbins 1 I University Laboratory of Physiology, Parks Road, Oxford and 2Renal Unit, Churchill Hospital, Oxford, U.K. (Accepted for publication 11 February 1989) Abstract. Arterial plasma potassium concentration ([K + ]a) is increased during exercise. This change is
sufficient to excite arterial chemoreceptors and stimulate ventilation (VE) in the anaesthetized cat. Moreover, changes in [K + ]a and ~'E are highly correlated during exercise, however the contribution that [K +]a makes to the control of breathing in man is not yet known. Four otherwise relatively healthy male hyperkalaemic renal patients had their VE measured before, during and after an intravenous infusion of dextrose and insulin to lower their [K + ]a. Thirty-six minutes after the infusion began [K + ]a had been reduced by ca. 2 mM. Ventilation was virtually unchanged throughout the experiment. These results suggest that [K + ]a does not significantly affect ~'E in this group of subjects. The assumptions that would need to be made to extrapolate this conclusion to the general population are discussed.
Control of Breathing; Human; Hyperkalaemia; Renal failure; Ventilation
Arterial plasma potassium concentration ([K + ]a) and ventilation (VE) are highly correlated throughout exercise (Band et al., 1985a; Conway et al., 1988; Newstead, 1988). In healthy subjects [K + ]a may reach 7 mM during exhaustive exercise (Conway et al., 1988). This is a level that excites arterial chemoreceptors (Linton and Band, 1985; Paterson and Nye, 1988) and stimulates VE in the anaesthetized cat (Band et al., 1985b). However, the contribution that [ K + ]a makes to the control of breathing in man is not yet known. In order to elucidate further a role for [K + ]a in ventilatory control, the effect of lowering plasma potassium on VE was examined. Subjects who were hyperkalaemic from renal failure were studied since lowering their [K + ]a is easier and less hazardous than elevating the [K + ]a of normal subjects. A preliminary account of some of the
Correspondence address: D. Paterson, University Laboratory of Physiology, Parks Road, Oxford OXI 3PT, U.K. 0034-5687/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)
394
D.J. PATERSON et al.
findings in this paper have already been communicated in abstract form (Friedland et al., 1988).
Methods Subjects. Four hyperkalaemic patients with renal failure, who were otherwise relatively healthy and without evidence of pulmonary disease, volunteered to have their '~'E measured before, during and after the lowering of [K + ]a with dextrose and insulin. Following verbal and written explanation of the aims of the study, informed consent was obtained. This was done in consultation with the subjects' physician. Approval for this investigation had been given by the Central Oxford Research Ethics Committee. The clinical characteristics and medication of each subject are given in table 1. Respiratory apparatus. Patients breathed air through a mouthpiece whilst wearing a nose clip. Minute ventilation and the partial pressures of the end-tidal gas were measured on a breath-by-breath basis using a pneumotachograph and turbine device (Howson et al., 1986) and a mass spectrometer (Centronic 200 MGA) respectively. This information was collected using a computer running a real time data acquisition program. One probleni associated with measuring VE at rest is that a mouthpiece and nose clip may sometimes cause a subject to hyperventilate. As a check to ensure that this was not occurring, VE was also measured at the beginning and end of the experimental protocol using a second method which did not employ a mouthpiece or nose clip. Subjects breathed air via a face mask and VE was measured by collecting the expirate and passing it through a dry gas meter (Parkinson-Cowan) which had previously been calibrated against a Tissot spirometer.
TABLE 1 Clinical characteristics and medications of subjects. Subject
Age/sex Weight (year) (kg)
BP* (mm Hg)
Cause of renal disease
Medication*
727
27/M
78
192/97
Nifedipine
728
49/M
62
134/63
Idiopathic renal failure Amyloid
729
48/M
66
128/77
730
56/M
86
168/84
Chronic glomerulonephritis Focal proliferative chronic glomerulonephritis
Hydrocortisone Fludrocortisone Nifedipine
* Average of 3 pre-dialysis blood pressures from the week preceding the study; * all subjects received multivitamin supplements, folic acid, oral phosphate binders and 1 alfacalcidol.
VE RESPONSE TO LOWERED [K +]a
395
Procedures. Subjects presented themselves to the laboratory before their haemodialysis session. A venous catheter was inserted into a superficial vein in the arm. Blood was drawn and the plasma analysed for [K + ] by flame photometry (Instrumentation Laboratories 943). Subjects who had venous K + levels that were greater than 5.5 mM were eligible to be subjects. Each subject was given time to become familiar with breathing through both systems prior to the start of data collection. A catheter was inserted into the brachial artery of the non-fistula arm from which blood samples (3 ml) could be taken into an heparinised syringe for measurement of the partial pressure of O: and COe (Pao~, Paco~) pH (pHa) (Coming 166 Micro Analyser), glucose (Yellow Springs, Model 23AM) and [K + ]a. A three lead ECG was positioned on the chest wall in the CM5 position (Blackburn et al., 1967) and heart rate was monitored (Rigel Cardiac Monitor 302). Oxygen saturation was also monitored by a pulse oximeter (Ohemeda Biox 3700). Subjects breathed air for 15 rain using the face mask apparatus while their VE was determined. The apparatus was then changed, and they breathed air through a mouthpiece for a further 15 rain. The control arterial blood sample was collected. Eight units of human Actrapid insulin in 75 ml of 50~o dextrose was then infused intravenously. Ventilation was measured continuously using the apparatus associated with the mouthpiece. Following the infusion, arterial blood was sampled every 6 rain. After 18 rain an infusion of 50 ml of 50% dextrose was given to lower the [K + ]a further. Three more arterial samples were then taken at 6 rain intervals. After this, the apparatus was changed and the subject breathed through the face mask again for the 15 rain.
Results
The cc.ntrol values for [K ÷ ]a, ventilation (mask and mouthpiece), glucose, blood gases and pH for each subject are shown in table 2 (line B). It can be seen that all subjects were hyperkalaemic, all had normal blood glucose levels, three of the four subjects were metabolically acidotic, and all were hypocapnic. The "qE obtained from ~reathing through the face mask and mouthpiece were indistinguishable. Figure 1 illustrates the average changes that occurred during the course of the experimental period. A clear drop in [K + ]a was brought about by the infusions of dextrose and insulin. Glucose levels rose following each infusion and then declined. Hypoglycaemia did not occur in any subject. Ventilation was virtually unchanged during the experiment, although there appeared to be a very slight fall in pHa. All subjects remained hypocapnic with an average Pao2 of 98.7 Torr. Thirty-six minutes after the first infusion (line A, table 2), the effect of dextrose and insulin was to lower [ K + ]a by 1.86 ± 0.36 mM. There was no apparent change in "¢E. Blood glucose and pHa were also similar to control values.
396
D.J. PATERSON et al.
[K+]a
(raM) VE (llmin) Glucose (raM)
7]
6 5
12 ] I,
10 8
z
i
I_
I
16 12 8 4
7.341 PH a 7.321
7.30J PaC02
(Torr)
33t
30
27 Pa02
(Torr)
100. I 90.1 infusion
6
infGsion
12
18
'
24
'
36
30
TIME (min)
Fig. 1. Arterial K ÷ and "~E responses to the infusion of eight units of human actrapid insulin in 75 ml of 50% dextrose (first upward pointing arrow), followed by a second infusion of 50 ml of 50% dextrose (second upward pointing arrow). Results for the four subjects are expressed as means + l SD. From top down the variables are, arterial K + (mM), expired minute ventilation (L/min), pH, partial pressures for arterial carbon dioxide and oxygen (Torr).
TABLE 2 [K ÷ ]a, VE, blood gases, pH and glucose for each subject before (B) and after (A) the dextrose and insulin infusions. Means and SD are shown. Subject
727 728 729 730
Mean SD
pHa
Paco2 (Torr)
Pao2 (Torr)
Glucose (mM)
[K ÷ ]a (mM)
'VE (mouth piece) (L/min)
"VE (face mask) (L/min)
B A B A B A B A
7.39 7.38 7.33 7.30 7.29 7.27 7.37 7.35
26.2 30.3 34.1 33.3 26.1 27.5 38.9 31.7
89.0 90.9 104.6 109.4 104.2 103.0 96.0 91.5
5.3 3.5 5.0 4.6 3.2 3.4 4.9 6.6
6.96 5.34 6.43 4.58 6.56 4.80 7.89 5.50
9.2 10.4 8.6 8.6 8.5 9.2
8.9 10.5 8.7 7.5 8.8 9.3 8.6 8.7
B
7.34 0.04 7.32 0.05
31.4 6.23 30.7 2.46
4.6 0.94 4.5 1.48
6.95 0.65 5.05 0.38
A
98.4 7.44 98.7 9.02
8.8 0.38 9.4 0.92
8.7 0.12 9.0 1.25
"~/E RESPONSE TO LOWERED [K+]a
397
Discussion
This study has shown that ventilation remained similar to control values in four hyperkalaemic subjects with renal failure after their [K + ]a was lowered by ca. 2 mM following an intravenous infusion of dextrose and insulin. Previous studies have suggested that changes in [K + ]a might be important in contributing to ventilatory control during exercise (Band et al., 1985b; Sneyd et al., 1988; Burger et al., 1988; Paterson and Nye, 1988). We have also observed that two moderately hyperkalaemic renal subjects reached values of [K + ]a similar to those of normal subjects (ca. 7 raM) after an exhaustive bout of exercise (Fnedland and Paterson, 1988). Changes in VE and [K + ]a are highly correlated throughout exercise and recovery in healthy subjects (Band et al., 1985a; Conway et al., 1988; Newstead, 1988) and renal subjects (unpublished observations). Arterial chemoreceptors in the anaesthetized cat are stimulated by rises in [ K + ]a that are comparable with those observed during exercise (Linton and Band, 1985; Paterson and Nye, 1988). This effect is potentiated in hypoxia and abolished by hyperoxia (Burger et al., 1988). Moreover, the stimulation of VE by hyperkalaemia in the cat is abolished when both the aortic and carotid body chemoreceptor nerves are sectioned (Band et al., 1985b). From this study there is no evidence to support a role for potassium in the control of VE. There are, however, several reasons why extrapolating this conclusion to the general population may not be correct. First, the subjects here were at rest, and it is during exercise that [K + ]a and "V'Eare correlated (Conway et al., 1988). Secondly, they were metabolically acidotic and hypocapnic, and it is possible that the prevailing acid drive (mean pH = 7.32 + 0.05) might obscure the effect any reduction in [K + ]a could have on VE. Thirdly, we have evidence which suggests that the arterial chemoreceptors of metabolically acidotic renal patients may not respond normally to hypoxia and hypercapnia (unpublished observations), and consequently it is possible that their carotid bodies may also be insensitive to changes in [K + ]a. Finally, the subjects were chronically hyperkalaemic, and the long-term effects of this on arterial chemoreceptors are not known. Furthermore, Band and Linton (1986) have shown that discharge from the arterial chemoreceptors of the cat adapts to a steady-state infusion of potassium. Thus the fact that altering [K + ]a did not affect'qE in these subjects does not necessarily imply that changes in potassium are unimportant for ventilatory control. Acknowledgements.This work was supported by the Wellcome Trust and the Nuffield Foundation. D.J.P. is a Hackett Scholar from the University of Western Australia.
References Band, D. M., M. Lim, R. A. F. Linton and C. B. Wolff(1985a). Changes in arterial plasma potassium during exercise. J. Physiol. (London) 328: 74-75P.
398
D.J. PATERSON et al.
Band, D.M., R. A. F. Linton, R. Kent and F.L. Kurer (1985b). The effect of peripheral chemodenervation on the ventilatory response to potassium. Respir. Physiol. 60: 217-225. Band, D. M and R. A. F. Linton (1986). The effect of potassium on carotid body chemoreceptor discharge in the anaesthetized cat. J. Physiol. (London) 381: 39-47. Blackburn, H., H.L. Taylor, N. Okamoto, P. Rantamargin, P.L. Mitchell and A.C. Kerkhov (1967). In: Physical Activity and the Heart, edited by M. Karvonen and A. Barry. Springfield, Illinois. Burger, R. E., J. A. Estavillo, P. Kumar, P. C. G. Nye and D.J. Paterson (1988). Effects of potassium, oxygen and carbon dioxide on the steady-state discharge of cat carotid body chemoreceptors. J. Physiol. (London) 401: 519-531. Conway, J., D.J. Paterson, E.S. Petersen and P.A. Robbins (1988). Changes in arterial potassium and ventilation in response to exercise in humans. J. Physiol. (London) 399: 36P. Friedland, J.S. and D.J. Paterson (1988). Potassium and fatigue. Lancet ii: 961-962. Friedland, J.S., D.O. Oliver, D.J. Paterson and P.A. Robbins (1988). The ventilatory response to the lowering of potassium with dextrose and insulin in patients with hyperkalaemia. J. Physiol. (London) 407: 30P. Howson, M.G., S. Khamnei, D.F. O'Connor and P.A. Robbins (1986). The properties of a turbine device for measuring respiratory volumes in man. J. Physiol. (London) 382: 12P. Linton, R.A.F. and D.M. Band (1985). The effect of potassium on carotid chemoreceptor activity and ventilation in the cat. Respir. Physiol. 59: 65-70. Newstead, C. G. (1988). The relationship between arterial potassium and ventilation during exercise in man. J. Physiol. (London)403: 101P. Paterson, D.J. and P. C. G. Nye (1988). The effect of beta adrenergic blockade on the carotid body response to hyperkalaemia in the cat. Respir. Physiol. 74: 229-238. Sneyd, J.R., R.A.F. Linton and D.M. Band (1988). Ventilatory effects of potassium during hyperoxia, normoxia and hypoxia in anaesthetized cats. Respir. Physiol. 72: 59-64.
393
RSP 01541
The ventilatory response to lowering potassium with dextrose and insulin in subjects with hyperkalaemia David J. Paterson ~, Jon. S. Friedland 2, Des. O. Oliver 2 and Peter A. Robbins 1 I University Laboratory of Physiology, Parks Road, Oxford and 2Renal Unit, Churchill Hospital, Oxford, U.K. (Accepted for publication 11 February 1989) Abstract. Arterial plasma potassium concentration ([K + ]a) is increased during exercise. This change is
sufficient to excite arterial chemoreceptors and stimulate ventilation (VE) in the anaesthetized cat. Moreover, changes in [K + ]a and ~'E are highly correlated during exercise, however the contribution that [K +]a makes to the control of breathing in man is not yet known. Four otherwise relatively healthy male hyperkalaemic renal patients had their VE measured before, during and after an intravenous infusion of dextrose and insulin to lower their [K + ]a. Thirty-six minutes after the infusion began [K + ]a had been reduced by ca. 2 mM. Ventilation was virtually unchanged throughout the experiment. These results suggest that [K + ]a does not significantly affect ~'E in this group of subjects. The assumptions that would need to be made to extrapolate this conclusion to the general population are discussed.
Control of Breathing; Human; Hyperkalaemia; Renal failure; Ventilation
Arterial plasma potassium concentration ([K + ]a) and ventilation (VE) are highly correlated throughout exercise (Band et al., 1985a; Conway et al., 1988; Newstead, 1988). In healthy subjects [K + ]a may reach 7 mM during exhaustive exercise (Conway et al., 1988). This is a level that excites arterial chemoreceptors (Linton and Band, 1985; Paterson and Nye, 1988) and stimulates VE in the anaesthetized cat (Band et al., 1985b). However, the contribution that [ K + ]a makes to the control of breathing in man is not yet known. In order to elucidate further a role for [K + ]a in ventilatory control, the effect of lowering plasma potassium on VE was examined. Subjects who were hyperkalaemic from renal failure were studied since lowering their [K + ]a is easier and less hazardous than elevating the [K + ]a of normal subjects. A preliminary account of some of the
Correspondence address: D. Paterson, University Laboratory of Physiology, Parks Road, Oxford OXI 3PT, U.K. 0034-5687/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)
394
D.J. PATERSON et al.
findings in this paper have already been communicated in abstract form (Friedland et al., 1988).
Methods Subjects. Four hyperkalaemic patients with renal failure, who were otherwise relatively healthy and without evidence of pulmonary disease, volunteered to have their '~'E measured before, during and after the lowering of [K + ]a with dextrose and insulin. Following verbal and written explanation of the aims of the study, informed consent was obtained. This was done in consultation with the subjects' physician. Approval for this investigation had been given by the Central Oxford Research Ethics Committee. The clinical characteristics and medication of each subject are given in table 1. Respiratory apparatus. Patients breathed air through a mouthpiece whilst wearing a nose clip. Minute ventilation and the partial pressures of the end-tidal gas were measured on a breath-by-breath basis using a pneumotachograph and turbine device (Howson et al., 1986) and a mass spectrometer (Centronic 200 MGA) respectively. This information was collected using a computer running a real time data acquisition program. One probleni associated with measuring VE at rest is that a mouthpiece and nose clip may sometimes cause a subject to hyperventilate. As a check to ensure that this was not occurring, VE was also measured at the beginning and end of the experimental protocol using a second method which did not employ a mouthpiece or nose clip. Subjects breathed air via a face mask and VE was measured by collecting the expirate and passing it through a dry gas meter (Parkinson-Cowan) which had previously been calibrated against a Tissot spirometer.
TABLE 1 Clinical characteristics and medications of subjects. Subject
Age/sex Weight (year) (kg)
BP* (mm Hg)
Cause of renal disease
Medication*
727
27/M
78
192/97
Nifedipine
728
49/M
62
134/63
Idiopathic renal failure Amyloid
729
48/M
66
128/77
730
56/M
86
168/84
Chronic glomerulonephritis Focal proliferative chronic glomerulonephritis
Hydrocortisone Fludrocortisone Nifedipine
* Average of 3 pre-dialysis blood pressures from the week preceding the study; * all subjects received multivitamin supplements, folic acid, oral phosphate binders and 1 alfacalcidol.
VE RESPONSE TO LOWERED [K +]a
395
Procedures. Subjects presented themselves to the laboratory before their haemodialysis session. A venous catheter was inserted into a superficial vein in the arm. Blood was drawn and the plasma analysed for [K + ] by flame photometry (Instrumentation Laboratories 943). Subjects who had venous K + levels that were greater than 5.5 mM were eligible to be subjects. Each subject was given time to become familiar with breathing through both systems prior to the start of data collection. A catheter was inserted into the brachial artery of the non-fistula arm from which blood samples (3 ml) could be taken into an heparinised syringe for measurement of the partial pressure of O: and COe (Pao~, Paco~) pH (pHa) (Coming 166 Micro Analyser), glucose (Yellow Springs, Model 23AM) and [K + ]a. A three lead ECG was positioned on the chest wall in the CM5 position (Blackburn et al., 1967) and heart rate was monitored (Rigel Cardiac Monitor 302). Oxygen saturation was also monitored by a pulse oximeter (Ohemeda Biox 3700). Subjects breathed air for 15 rain using the face mask apparatus while their VE was determined. The apparatus was then changed, and they breathed air through a mouthpiece for a further 15 rain. The control arterial blood sample was collected. Eight units of human Actrapid insulin in 75 ml of 50~o dextrose was then infused intravenously. Ventilation was measured continuously using the apparatus associated with the mouthpiece. Following the infusion, arterial blood was sampled every 6 rain. After 18 rain an infusion of 50 ml of 50% dextrose was given to lower the [K + ]a further. Three more arterial samples were then taken at 6 rain intervals. After this, the apparatus was changed and the subject breathed through the face mask again for the 15 rain.
Results
The cc.ntrol values for [K ÷ ]a, ventilation (mask and mouthpiece), glucose, blood gases and pH for each subject are shown in table 2 (line B). It can be seen that all subjects were hyperkalaemic, all had normal blood glucose levels, three of the four subjects were metabolically acidotic, and all were hypocapnic. The "qE obtained from ~reathing through the face mask and mouthpiece were indistinguishable. Figure 1 illustrates the average changes that occurred during the course of the experimental period. A clear drop in [K + ]a was brought about by the infusions of dextrose and insulin. Glucose levels rose following each infusion and then declined. Hypoglycaemia did not occur in any subject. Ventilation was virtually unchanged during the experiment, although there appeared to be a very slight fall in pHa. All subjects remained hypocapnic with an average Pao2 of 98.7 Torr. Thirty-six minutes after the first infusion (line A, table 2), the effect of dextrose and insulin was to lower [ K + ]a by 1.86 ± 0.36 mM. There was no apparent change in "¢E. Blood glucose and pHa were also similar to control values.
396
D.J. PATERSON et al.
[K+]a
(raM) VE (llmin) Glucose (raM)
7]
6 5
12 ] I,
10 8
z
i
I_
I
16 12 8 4
7.341 PH a 7.321
7.30J PaC02
(Torr)
33t
30
27 Pa02
(Torr)
100. I 90.1 infusion
6
infGsion
12
18
'
24
'
36
30
TIME (min)
Fig. 1. Arterial K ÷ and "~E responses to the infusion of eight units of human actrapid insulin in 75 ml of 50% dextrose (first upward pointing arrow), followed by a second infusion of 50 ml of 50% dextrose (second upward pointing arrow). Results for the four subjects are expressed as means + l SD. From top down the variables are, arterial K + (mM), expired minute ventilation (L/min), pH, partial pressures for arterial carbon dioxide and oxygen (Torr).
TABLE 2 [K ÷ ]a, VE, blood gases, pH and glucose for each subject before (B) and after (A) the dextrose and insulin infusions. Means and SD are shown. Subject
727 728 729 730
Mean SD
pHa
Paco2 (Torr)
Pao2 (Torr)
Glucose (mM)
[K ÷ ]a (mM)
'VE (mouth piece) (L/min)
"VE (face mask) (L/min)
B A B A B A B A
7.39 7.38 7.33 7.30 7.29 7.27 7.37 7.35
26.2 30.3 34.1 33.3 26.1 27.5 38.9 31.7
89.0 90.9 104.6 109.4 104.2 103.0 96.0 91.5
5.3 3.5 5.0 4.6 3.2 3.4 4.9 6.6
6.96 5.34 6.43 4.58 6.56 4.80 7.89 5.50
9.2 10.4 8.6 8.6 8.5 9.2
8.9 10.5 8.7 7.5 8.8 9.3 8.6 8.7
B
7.34 0.04 7.32 0.05
31.4 6.23 30.7 2.46
4.6 0.94 4.5 1.48
6.95 0.65 5.05 0.38
A
98.4 7.44 98.7 9.02
8.8 0.38 9.4 0.92
8.7 0.12 9.0 1.25
"~/E RESPONSE TO LOWERED [K+]a
397
Discussion
This study has shown that ventilation remained similar to control values in four hyperkalaemic subjects with renal failure after their [K + ]a was lowered by ca. 2 mM following an intravenous infusion of dextrose and insulin. Previous studies have suggested that changes in [K + ]a might be important in contributing to ventilatory control during exercise (Band et al., 1985b; Sneyd et al., 1988; Burger et al., 1988; Paterson and Nye, 1988). We have also observed that two moderately hyperkalaemic renal subjects reached values of [K + ]a similar to those of normal subjects (ca. 7 raM) after an exhaustive bout of exercise (Fnedland and Paterson, 1988). Changes in VE and [K + ]a are highly correlated throughout exercise and recovery in healthy subjects (Band et al., 1985a; Conway et al., 1988; Newstead, 1988) and renal subjects (unpublished observations). Arterial chemoreceptors in the anaesthetized cat are stimulated by rises in [ K + ]a that are comparable with those observed during exercise (Linton and Band, 1985; Paterson and Nye, 1988). This effect is potentiated in hypoxia and abolished by hyperoxia (Burger et al., 1988). Moreover, the stimulation of VE by hyperkalaemia in the cat is abolished when both the aortic and carotid body chemoreceptor nerves are sectioned (Band et al., 1985b). From this study there is no evidence to support a role for potassium in the control of VE. There are, however, several reasons why extrapolating this conclusion to the general population may not be correct. First, the subjects here were at rest, and it is during exercise that [K + ]a and "V'Eare correlated (Conway et al., 1988). Secondly, they were metabolically acidotic and hypocapnic, and it is possible that the prevailing acid drive (mean pH = 7.32 + 0.05) might obscure the effect any reduction in [K + ]a could have on VE. Thirdly, we have evidence which suggests that the arterial chemoreceptors of metabolically acidotic renal patients may not respond normally to hypoxia and hypercapnia (unpublished observations), and consequently it is possible that their carotid bodies may also be insensitive to changes in [K + ]a. Finally, the subjects were chronically hyperkalaemic, and the long-term effects of this on arterial chemoreceptors are not known. Furthermore, Band and Linton (1986) have shown that discharge from the arterial chemoreceptors of the cat adapts to a steady-state infusion of potassium. Thus the fact that altering [K + ]a did not affect'qE in these subjects does not necessarily imply that changes in potassium are unimportant for ventilatory control. Acknowledgements.This work was supported by the Wellcome Trust and the Nuffield Foundation. D.J.P. is a Hackett Scholar from the University of Western Australia.
References Band, D. M., M. Lim, R. A. F. Linton and C. B. Wolff(1985a). Changes in arterial plasma potassium during exercise. J. Physiol. (London) 328: 74-75P.
398
D.J. PATERSON et al.
Band, D.M., R. A. F. Linton, R. Kent and F.L. Kurer (1985b). The effect of peripheral chemodenervation on the ventilatory response to potassium. Respir. Physiol. 60: 217-225. Band, D. M and R. A. F. Linton (1986). The effect of potassium on carotid body chemoreceptor discharge in the anaesthetized cat. J. Physiol. (London) 381: 39-47. Blackburn, H., H.L. Taylor, N. Okamoto, P. Rantamargin, P.L. Mitchell and A.C. Kerkhov (1967). In: Physical Activity and the Heart, edited by M. Karvonen and A. Barry. Springfield, Illinois. Burger, R. E., J. A. Estavillo, P. Kumar, P. C. G. Nye and D.J. Paterson (1988). Effects of potassium, oxygen and carbon dioxide on the steady-state discharge of cat carotid body chemoreceptors. J. Physiol. (London) 401: 519-531. Conway, J., D.J. Paterson, E.S. Petersen and P.A. Robbins (1988). Changes in arterial potassium and ventilation in response to exercise in humans. J. Physiol. (London) 399: 36P. Friedland, J.S. and D.J. Paterson (1988). Potassium and fatigue. Lancet ii: 961-962. Friedland, J.S., D.O. Oliver, D.J. Paterson and P.A. Robbins (1988). The ventilatory response to the lowering of potassium with dextrose and insulin in patients with hyperkalaemia. J. Physiol. (London) 407: 30P. Howson, M.G., S. Khamnei, D.F. O'Connor and P.A. Robbins (1986). The properties of a turbine device for measuring respiratory volumes in man. J. Physiol. (London) 382: 12P. Linton, R.A.F. and D.M. Band (1985). The effect of potassium on carotid chemoreceptor activity and ventilation in the cat. Respir. Physiol. 59: 65-70. Newstead, C. G. (1988). The relationship between arterial potassium and ventilation during exercise in man. J. Physiol. (London)403: 101P. Paterson, D.J. and P. C. G. Nye (1988). The effect of beta adrenergic blockade on the carotid body response to hyperkalaemia in the cat. Respir. Physiol. 74: 229-238. Sneyd, J.R., R.A.F. Linton and D.M. Band (1988). Ventilatory effects of potassium during hyperoxia, normoxia and hypoxia in anaesthetized cats. Respir. Physiol. 72: 59-64.