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1 Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, UK
2 Departamento De Ciencias Biológicas y Fisiológicas, Instituto de Investigación de Altura, Universidad Peruana Cayetano Heredia, Lima 100, Peru
3 NMHEMC Research Foundation, 361, Big Horn Ridge, NE, Albuquerque, NM 87122, USA
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Abstract |
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(Received 13 March 2005;
accepted after revision 27 April 2005;
first published online 28 April 2005)
Corresponding author L. Norcliffe: Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, UK. Email: ugmljn{at}leeds.ac.uk
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Introduction |
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Chronic high-altitude exposure is associated with polycythaemia, although the extent of this varies between populations. The increase in haematocrit is particularly pronounced in Andean high-altitude dwellers (Beall et al. 2002), and even more so in those who suffer from chronic mountain sickness (CMS) (Milledge & Sorensen, 1972). CMS is characterized by haematocrits greater than 60% and various symptoms including fatigue and cognitive impairment (Leon-Velarde et al. 1994). Ultimately it leads to heart failure (Penaloza & Sime, 1971) and death.
Many of the symptoms of CMS are thought to be caused by cerebral hypoxia (Sorensen et al. 1974; Arregui et al. 1991), and this may be exacerbated by the low cerebral blood flow caused by the high viscosity of the blood (Massik et al. 1987).
There have been a number of studies which have investigated cerebrovascular control in Andean dwellers, and these have indicated an impaired vasodilatation to hypercapnia (Appenzeller et al. 2004), and to combined hypoxia and hypercapnia during sleep apnoea (Sun et al. 1996), but it is not known whether the vasodilatation to hypoxia alone, as well as the vasconstriction to hypocapnia, are also impaired. Cerebral autoregulation may also be impaired (Arregui et al. 1991; Sun et al. 1996), and this would cause cerebral blood flow to become deficient during decreases in blood pressure, for example during postural changes. The reason for these apparently abnormal cerebrovascular responses is unknown, but one possibility is that they may be related to the high haematocrit, as Andeans, who are both hypoxic and polycythaemic, have impaired cerebrovascular responses to changes in oxygen and carbon dioxide levels (Sun et al. 1996), whereas Tibetans, who are also hypoxic but less polycythaemic, have apparently normal responses (Jansen et al. 2000). These are not the only factors that may affect cerebrovascular control in these high-altitude dwellers and, in addition to possible effects of chronic hypoxia and high haematocrit levels, the different populations would have quite different genetic constitutions, and the possible influence of this should not be ignored. There may also be other environmental differences.
The present study was undertaken to try to determine the importance of chronic altitude-induced hypoxia and polycythaemia in influencing the chemical control of the cerebral circulation in Andeans. We studied responses of the cerebral circulation to hypoxia and hypocapnia, both separately and combined, in a high-altitude Andean population of presumed genetic similarity. Some of the subjects suffered from CMS and had haematocrits in excess of 60%, and this would thus allow the influence (amongst possibly other things) of haematocrit to be examined. To examine the possible effects of relief of the hypoxia, all subjects were taken to sea level, and studies of cerebrovascular responses were repeated within a day of arrival. We compared results from both high-altitude groups with those from sea-level residents studied at sea level to determine whether cerebrovascular control was different in these chronically hypoxic subjects.
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Methods |
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Subjects
Eighteen male high-altitude dwellers were recruited; all had been born and had lived all their lives in CP. Their previous visit to low altitude had been at least 6 months prior to the study. None had worked as a miner. The subjects were recruited from those who had taken part in our recently reported studies (Claydon et al. 2004, 2005). Nine of the subjects were known to suffer from CMS. On arrival at the laboratory in CP, subjects gave a detailed clinical history and had all test procedures explained. Peripheral haematocrit (Hct) was measured, and CMS scores (CMSSco) were calculated using the scoring system based on the absence or severity of the 10 most common clinical symptoms and signs of CMS (Leon-Velarde et al. 2003). The nine normal subjects had Hct <60% and were categorized as high-altitude normals (HA). The nine CMS subjects all had Hct >65% as well as high CMS scores. Eight sea-level male control subjects (age 33 ± 5 years) were also recruited from the University of Leeds. All were healthy normotensive volunteers and were assumed to have normal haematocrits. Figure 1 illustrates the time course of the procedures.
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Transcranial Doppler ultrasonography was used to measure changes in middle cerebral artery mean blood flow velocity (MCAVm), from which changes in cerebral blood flow were deduced in accordance with previous validation studies (Bishop et al. 1986; Aaslid et al. 1989). A 2 mHz pulsed-wave Doppler probe (Multi-Dop T2, TCD-8.01; DWL Elektronische System GmbH, Sipplingen, Germany) was mounted on a headband over the transcranial window. The middle cerebral artery (MCA) wave form was located at the optimal depth and the ultrasound probe fixed into position. Beat-to-beat values of MCAVm were recorded and analysed off-line after completion of the study. Blood pressure (autoinflating sphygmomanometer), heart rate (ECG) and arterial oxygen saturation (finger oximetry) were also measured throughout the study (Hewlett Packard 78325C, Boebringen, Germany).
Protocol 1: cerebrovascular responses to hypoxia
The protocol was designed to determine cerebrovascular responses to isocapnic hypoxia. Subjects were seated and breathed through a mouthpiece for a minimum of 10 min whilst recordings were stabilized. Dynamic end-tidal forcing was used to manipulate end-tidal gases (Robbins et al. 1982), which were assumed to be representative of arterial blood gases. The technique is a fast-flow breath-by-breath method using voltage-gated valves to alter the flow of inspiratory gases in order to clamp or forcibly change the end-tidal gases. Throughout all procedures, brachial blood pressure and arterial oxygen saturation were measured using the autoinflating sphygmomanometer and finger oximeter, respectively.
The subject's (PET,CO2) was held close to predetermined resting levels throughout the procedure. (PET,O2) was held at 100 mmHg for 10 min to establish a steady state. It was then dropped in a single step to 50 mmHg for 20 min, and recordings of cerebral blood velocity were taken throughout. Cerebrovascular responses to hypoxia were taken as the percentage changes in MCA velocity that occurred following the step decrease in (PET,O2) during the steady state, from minute 8 to minute 20.
Protocol 2: cerebrovascular responses to hypocapnia
The protocol was designed to determine cerebrovascular reactivity to hypocapnia with end-tidal oxygen clamped constant at two levels: normoxia (PET,O2 100 mmHg) and hypoxia (PET,O2 50 mmHg). Subjects breathed either normoxic or hypoxic gases with carbon dioxide unclamped until in a steady state. (PET,CO2) was then decreased over a range of (PET,CO2) levels by instructing the subjects to hyperventilate by varying amounts. Cerebral responses to hypocapnia were calculated using linear regression of the relationship between (PET,CO2) and change in MCA velocity (e.g. Fig. 2). Data points were only included in the linear range and where correlation coefficients were statistically significant. The gradient of the relationship was used to measure the vascular reactivity of the cerebral circulation.
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All data are expressed as means ± standard errors of the means (S.E.M.). Spearman ranked correlation coefficients were used to assess correlations between variables. Unpaired t tests were used to compare the HA and CMS groups. Kolmogorov and Smirnov assumption methods were used to examine data for normal distribution, and on the basis of these findings the appropriate parametric or nonparametric ANOVA test was used to compare differences in responses of groups at CP, Lima and Leeds to the various procedures. GraphPad Instat version 3.00 for Macintosh (Graph Pad software, San Diego, CA, USA) was used to perform all statistical analyses. P < 0.05 was considered significant.
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Results |
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During normoxia (PET,O2 100 mmHg), blood pressure and heart rate were not significantly different between the two altitude groups or at the two locations (Table 2). During normoxia (PET,O2 100 mmHg), diastolic blood pressure was significantly lower in the sea-level controls compared with HA and CMS at CP (both P < 0.01). Heart rate was significantly higher in the sea-level controls compared with high-altitude subjects at CP and Lima (all P < 0.05).
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Cerebrovascular responses to hypoxia
Satisfactory data were obtained from eight HA subjects, nine CMS patients and eight sea-level controls. At CP, the decrease in inspired oxygen during the protocol reduced arterial oxygen saturation in HA from 96.8 ± 0.2 to 86.9 ± 0.3%, and in CMS from 95.3 ± 0.4 to 86.5 ± 0.4%. At Lima, hypoxia reduced oxygen saturation in HA from 96.6 ± 0.4 to 86.5 ± 0.9%, and in CMS from 94.6 ± 0.8 to 84.3 ± 0.9%. These changes were similar in both groups at both locations. Heart rate and blood pressure changes were similar in all tests (Table 3).
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Complete data from CP and Lima, with significant correlations between MCAVm and (PET,CO2) (e.g. Fig. 2), were obtained from eight HA subjects and eight CMS patients. Data were unsatisfactory from two subjects due to poor-quality ultrasound signals resulting in insignificant correlation coefficients of the (PET,CO2)–MCAVm relationships. All remaining (PET,CO2)–MCAVm gradients were significantly correlated (mean correlation coefficient 0.89 ± 0.1). The range of changes in carbon dioxide were similar in all studies: at CP during hypoxia, HA changed from 28.0 ± 0.50 to 12.4 ± 0.4 mmHg, CMS from 31.4 ± 0.7 to 13.7 ± 0.9 mmHg; during normoxia, HA changed from 31.4 ± 2.2 to 14.5 ± 1.28 mmHg, CMS from 31.3 ± 0.7 to 15.1 ± 1.2 mmHg. At Lima during hypoxia, HA changed from 32.8 ± 0.8 to 15.0 ± 0.6 mmHg, CMS from 31.4 ± 0.7 to 15.6 ± 0.9 mmHg; during normoxia, HA changed from 35.8 ± 0.6 to 19.3 ± 1.5 mmHg, CMS from 35.6 ± 0.6 to 19.8 ± 0.5 mmHg). The range of change of carbon dioxide in sea-level controls was from 35.8 ± 1.0 to 18.8 ± 0.93 mmHg.
Comparison between results from all subjects revealed that baseline values of carbon dioxide at CP were lower in HA than in CMS (P < 0.01). They were also lower during normoxia in HA at CP than in the same subjects at Lima (P < 0.05), and lower than in sea-level controls (P < 0.001). Hyperventilation–hypocapnic values during normoxia were consequently lower in the HA group than in CMS at CP (P < 0.001) and lower than in the same group at Lima (P < 0.01). They were also lower than in sea-level controls (P < 0.01). The ranges of change of carbon dioxide induced by hyperventilation, however, were similar in all tests, and adequate to allow us to construct hypocapnic linear regression lines. MCAVm values were only included in the linear range.
During normoxia, there was no significant difference between the sensitivities of the cerebral circulation to hypocapnia in the two groups and at both locations (Fig. 4). The changes in sensitivity at CP and Lima in the HA subjects were 2.85 ± 0.29 and 2.55 ± 0.27% mmHg–1, and in CMS the corresponding values were 2.97 ± 0.49 and 2.60 ± 0.22% mmHg–1. During hypoxia, the sensitivities of the cerebral velocities were again similar in both groups. However in both groups, sensitivity was significantly less in Lima (Fig. 5). In HA it decreased from 3.29 ± 0.34 to 2.17 ± 0.23% mmHg–1 (P < 0.05), and in CMS from 3.23 ± 0.24 to 1.86 ± 0.16% mmHg–1 (P < 0.01).
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Discussion |
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The first main finding of this study was that there was no difference in the responses of the cerebral circulation to hypoxia or hypocapnia, separately or combined, between high-altitude residents with and without CMS, either determined at high altitude or within 24 h of arriving at sea level. The other main finding was that upon arrival at sea level, responses in both groups to hypoxia increased and, during hypoxia, the responses to hypocapnia were smaller. The responses to hypoxia in the high-altitude dwellers at sea level were similar to those in normal sea-level residents. Responses to normoxic hypocapnia in high-altitude dwellers, however, were greater than those in sea-level residents.
There has been a previous report which has suggested that CMS patients may have different cerebrovascular responses compared with high-altitude normals (Sun et al. 1996), and this would initially seem to be at variance with our results. The basis for the suggestion of different reactivities was that, during extreme hypoxia caused by sleep apnoea, cerebral flow decreased in CMS patients and increased in HA normals. However, the degree of hypoxia would have been considerably greater, particularly in the CMS patients, and very different from our moderate hypoxic stimulus. Interestingly, a recent report has indicated that hypoxia increases cerebral blood flow when subjects are awake, but decreases it during sleep (Meadows et al. 2004)
The mechanisms that cause the cerebrovascular response to hypoxia to be blunted at altitude are not known. One possibility is that it may be related to the release of vasoactive mediators, such as nitric oxide (NO). Acute hypoxia induces cerebral vasodilatation mainly through the release of NO (Van Mil et al. 2002). However, chronic hypoxia leads to a decline in nitric oxide synthase (NOS) levels (Mbaku et al. 2003), and it is possible that during chronic hypoxia at high altitude, the release of NO in response to acute hypoxia would be blunted. It is also possible that the sensitivity of the cerebral circulation to NO may be affected by chronic hypoxia and its alleviation. This suggestion is supported by a recent finding that NO donation causes a greater increase in cerebral flow in high-altitude dwellers after establishment of normoxia at sea level (Appenzeller et al. 2004). Another factor to be taken into consideration in our study is that carbon dioxide was higher at sea level during the hypoxia protocol. This may have had an effect on the sensitivity of the cerebral vessels to hypoxia. Whatever the mechanism responsible for the changes in reactivity, it does seem to take effect very rapidly because, within less than 24 h after arrival at sea level, responses were altered.
The results of the carbon dioxide reactivity tests are particularly intriguing. Although baseline carbon dioxide values were lower during concomitant hypoxia in the HA group at CP, this is unlikely to explain the difference in reactivity because reactivity was studied over a wide and overlapping linear range. Furthermore, in CMS patients, baseline values at CP were similar to those at Lima and cerebrovascular reactivity to hypocapnia showed the same change as in the HA subjects. We can only speculate on the possible reasons why the response of the cerebral blood flow velocity to hypocapnia were smaller at Lima that at CP, but only during concomitant hypoxia. At Lima, subjects had been normoxic and relatively normocapnic for between 12 and 18 h, and these changes in blood gas composition may have been responsible for the altered cerebrovascular reactivity to hypocapnia during hypoxia. Although the mechanism is uncertain, it is possible that NO might also have been involved in these changes. NO donation has been shown to blunt hypocapnic cerebral vasoconstriction (Lavi et al. 2003). Acute hypoxia increases flow and increases NO release. So, following the relief of the chronic hypoxia by descent to Lima when NOS increases, the acute hypoxia causes a greater release of NO and this would explain the reduction in the response to hypocapnia.
The altered cerebral blood flow responses at sea level implies that the adaptation to hypobaric hypoxia results in alteration of cerebrovascular reactivity in two ways: the vasodilatation induced by hypoxia is decreased, and the vasoconstriction induced by hypocapnia is exaggerated. In both cases this would lead to a reduction in cerebral blood flow and could be regarded as a potential maladaptation. However, by restricting blood flow it may have the benefit of protecting against cerebral oedema. Interestingly, bringing the subjects to sea level quickly alters cerebrovascular responses, suggesting that the change in cerebral control is rapidly reversible. This is supported by comparison of data with sea-level controls. Responses in high-altitude subjects to hypoxia were smaller at CP but similar at Lima to those in sea-level residents. Responses to normoxic hypocapnia, however, did not change and remained greater than those in sea level subjects.
One of the principal aims of this research was to try to determine whether cerebrovascular responses to changes in oxygen and carbon dioxide differed in subjects with different haematocrit values. The finding of identical cerebrovascular responses in subjects with varying degrees of polycythaemia suggests that haematocrit does not alter cerebrovascular control. Although we examined responses in subjects of presumed similar genetic constitutions in HA and CMS groups, we should perhaps insert a word of caution, as there may be other relevant differences between the CMS patients and the healthy Andeans. Furthermore, when relating the results of Andeans to sea-level subjects, the possible influences of both genetic and environmental differences must be taken into consideration. The enhanced vasodilatation in response to hypoxia, and decreased vasoconstriction to hypocapnia during hypoxia following sea-level descent, suggest that cerebrovascular control is impaired during chronic hypobaric hypoxia. However, this impairment is temporary as it is rapidly reversible within less than a day after arrival at low altitude. The changes in cerebrovascular reactivity have been clearly established, although we can only speculate on the likely mechanisms. What seems to be surprising is the speed with which these changes occurred, and it would be of interest to examine whether the changes could be detected within an even shorter period of time.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Appenzeller O, Passino C, Roach R, Gamboa J, Gamboa A, Bernardi L, Bonfichi M & Malcovati L (2004). Cerebral vasoreactivity in Andeans and headache at sea level. J Neurol Sci 219, 101–106.[CrossRef][Medline]
Arregui
A, Cabrera
J, Leon-Velarde
F, Paredes
S, Viscarra
D
&
Arbaiza
D (1991). High prevalence of migraine in a high-altitude population. Neurology
41, 1668–1669.
Beall
CM, Decker
MJ, Brittenham
GM, Kushner
I, Gebremedhin
A
&
Strohl
KP (2002). An Ethiopian pattern of human adaptation to high-altitude hypoxia. Proc Natl Acad Sci U S A
99, 17215–17218.
Bishop
CC, Powell
S, Rutt
D
&
Browse
NL (1986). Transcranial Doppler measurement of middle cerebral artery blood flow velocity: a validation study. Stroke
17, 913–915.
Chiodi
H (1957). Respiratory adaptations to chronic high altitude hypoxia. J Appl Physiol
10, 81–87.
Claydon
VE, Norcliffe
LJ, Moore
JP, Rivera
M, Leon-Velarde
F, Appenzeller
O
&
Hainsworth
R (2005). Cardiovascular responses to orthostatic stress in healthy altitude dwellers, and altitude residents with chronic mountain sickness. Exp Physiol
90, 103–110.
Claydon
VE, Norcliffe
LJ, Moore
JP, Rivera
ChM, Leon-Velarde
F, Appenzeller
O
&
Hainsworth
R (2004). Orthostatic tolerance and blood volumes in Andean high altitude dwellers. Exp Physiol
89, 565–571.
Jansen
GF, Krins
A, Basnyat
B, Bosch
A
&
Odoom
JA (2000). Cerebral autoregulation in subjects adapted and not adapted to high altitude. Stroke
31, 2314–2318.
Lassen
NA
&
Christensen
MS (1976). Physiology of cerebral blood flow. Br J Anaesth
48, 719–734.
Lavi
S, Egbarya
R, Lavi
R
&
Jacob
G (2003). Role of nitric oxide in the regulation of cerebral blood flow in humans: chemoregulation versus mechanoregulation. Circulation
107, 1901–1905.
Leon-Velarde
F, Arregui
A, Vargas
M, Huicho
L
&
Acosta
R (1994). Chronic mountain sickness and chronic lower respiratory tract disorders. Chest
106, 151–155.
Leon-Velarde F, McCullough RG, McCullough RE & Reeves JT (2003). Proposal for scoring severity in chronic mountain sickness (CMS). Background and conclusions of the CMS Working Group. Adv Exp Med Biol 543, 339–354.[Medline]
Massik
J, Tang
YL, Hudak
ML, Koehler
RC, Traystman
RJ
&
Jones
MD
Jr (1987). Effect of hematocrit on cerebral blood flow with induced polycythemia. J Appl Physiol
62, 1090–1096.
Mbaku
EM, Zhang
L, Pearce
WJ, Duckles
SP
&
Buchholz
J (2003). Chronic hypoxia alters the function of NOS nerves in cerebral arteries of near-term fetal and adult sheep. J Appl Physiol
94, 724–732.
Meadows
GE, O'Driscoll
DM, Simonds
AK, Morrell
MJ
&
Corfield
DR (2004). Cerebral blood flow response to isocapnic hypoxia during slow-wave sleep and wakefulness. J Appl Physiol
97, 1343–1348.
Milledge
JS
&
Sorensen
SC (1972). Cerebral arteriovenous oxygen difference in man native to high altitude. J Appl Physiol
32, 687–689.
Otis SM, Rossman ME, Schneider PA, Rush MP & Ringelstein EB (1989). Relationship of cerebral blood flow regulation to acute mountain sickness. J Ultrasound Med 8, 143–148.[Abstract]
Penaloza D & Sime F (1971). Chronic cor pulmonale due to loss of altitude acclimatization (chronic mountain sickness). Am J Med 50, 728–743.[CrossRef][Medline]
Poulin MJ, Fatemian M, Tansley JG, O'Connor DF & Robbins PA (2002). Changes in cerebral blood flow during and after 48 h of both isocapnic and poikilocapnic hypoxia in humans. Exp Physiol 87, 633–642.[Abstract]
Robbins
PA, Swanson
GD, Micco
AJ
&
Schubert
WP (1982). A fast gas-mixing system for breath-to-breath respiratory control studies. J Appl Physiol
52, 1358–1362.
Serrador
JM, Picot
PA, Rutt
BK, Shoemaker
JK
&
Bondar
RL (2000). MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke
31, 1672–1678.
Sorensen
SC, Lassen
NA, Severinghaus
JW, Coudert
J
&
Zamora
MP (1974). Cerebral glucose metabolism and cerebral blood flow in high-altitude residents. J Appl Physiol
37, 305–310.
Sun
S, Oliver-Pickett
C, Ping
Y, Micco
AJ, Droma
T, Zamudio
S, Zhuang
J, Huang
SY, McCullough
RG, Cymerman
A
&
Moore
LG (1996). Breathing and brain blood flow during sleep in patients with chronic mountain sickness. J Appl Physiol
81, 611–618.
Van Mil
AH, Spilt
A, Van Buchem
MA, Bollen
EL, Teppema
L, Westendorp
RG
&
Blauw
GJ (2002). Nitric oxide mediates hypoxia-induced cerebral vasodilation in humans. J Appl Physiol
92, 962–966.
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MCAVm (%), percentage change in middle cerebral artery blood flow velocity; r, correlation coefficient (P < 0.001); the gradient of the relationship was taken as a measure of cerebral reactivity to carbon dioxide.
