Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 103: 518-523, 2007. First published April 26, 2007; doi:10.1152/japplphysiol.01429.2006
8750-7587/07 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
103/2/518    most recent
01429.2006v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jansen, G. F. A.
Right arrow Articles by Ince, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jansen, G. F. A.
Right arrow Articles by Ince, C.

Role of the altitude level on cerebral autoregulation in residents at high altitude

Gerard F. A. Jansen,1 Anne Krins,1 Buddha Basnyat,2 Joseph A. Odoom,1 and Can Ince3

1Department of Anesthesiology and 3Department of Physiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; and 2Nepal International Clinic, Kathmandu, Nepal

Submitted 16 December 2006 ; accepted in final form 24 April 2007


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Cerebral autoregulation is impaired in Himalayan high-altitude residents who live above 4,200 m. This study was undertaken to determine the altitude at which this impairment of autoregulation occurs. A second aim of the study was to test the hypothesis that administration of oxygen can reverse this impairment in autoregulation at high altitudes. In four groups of 10 Himalayan high-altitude dwellers residing at 1,330, 2,650, 3,440, and 4,243 m, arterial oxygen saturation (SaO2), blood pressure, and middle cerebral artery blood velocity were monitored during infusion of phenylephrine to determine static cerebral autoregulation. On the basis of these measurements, the cerebral autoregulation index (AI) was calculated. Normally, AI is between zero and 1. AI of 0 implies absent autoregulation, and AI of 1 implies intact autoregulation. At 1,330 m (SaO2 = 97%), 2,650 m (SaO2 = 96%), and 3,440 m (SaO2 = 93%), AI values (mean ± SD) were, respectively, 0.63 ± 0.27, 0.57 ± 0.22, and 0.57 ± 0.15. At 4,243 m (SaO2 = 88%), AI was 0.22 ± 0.18 (P < 0.0005, compared with AI at the lower altitudes) and increased to 0.49 ± 0.23 (P = 0.008, paired t-test) when oxygen was administered (SaO2 = 98%). In conclusion, high-altitude residents living at 4,243 m have almost total loss of cerebral autoregulation, which improved during oxygen administration. Those people living at 3,440 m and lower have still functioning cerebral autoregulation. This study showed that the altitude region between 3,440 and 4,243 m, marked by SaO2 in the high-altitude dwellers of 93% and 88%, is a transitional zone, above which cerebral autoregulation becomes critically impaired.

cerebral circulation; hypoxia

THE BLOOD FLOW TO THE BRAIN is autoregulated, which means that, between mean arterial blood pressure (MAP) values of 60 and 160 mmHg, ~60 ml blood·100 g brain tissue–1·min–1 is delivered. Loss of cerebral autoregulation (CA) is thought to be rare, and most often reported in severe brain pathology, such as in ischemic stroke (31), traumatic brain injury (6), after cardiac arrest (36), and in malignant hypertension (16). In these patients, cerebral blood flow (CBF) fluctuates parallel with arterial blood pressure, implicating that a decrease in blood pressure can jeopardize cerebral perfusion, whereas an increase in blood pressure may cause cerebral edema.

Impaired CA has also been reported in healthy lowland subjects when they are exposed to high altitudes. Measurements in mountain climbers entering 5,500 m (22) or 4,243 m (17) revealed that middle cerebral artery (MCA) blood flow velocity (Vmca) changes along with blood pressure. In addition, in newcomers at 3,900 m, CA is reduced during sleep but not during wakefulness (2). Also in Sherpas in Nepal who reside permanently above 4,000 m and who are known for their superior exercise capacity under extreme hypoxia, CA is impaired (17).

The observation that in newcomers to high altitude and in permanent high-altitude residents CA is lost may suggest that CA is a reversible response of the cerebral vessel tone regulation to the hypoxia of high altitude. In support, animal studies demonstrate that, during acute hypoxia, CA is impaired when the arterial PO2 is below 25 Torr, values that are not compatible with sustained life at altitude (13, 20).

We hypothesize that CA is intact in high-altitude residents when they live at lower altitudes, but the altitude where autoregulation is lost remains unknown. We further tested the hypothesis that the administration of oxygen restores a totally impaired autoregulation. It is important to understand CBF regulation under conditions of high-altitude hypoxia, since high-altitude hypoxia affects workers and tourists and at least some 140 million persons who reside at altitudes above 2,500 m worldwide. In this study, we investigated CA at various altitude levels and we also studied whether the impaired autoregulation at the highest altitude may be corrected with the administration of oxygen.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Four groups of 10 Sherpas each were investigated in Nepal at four altitude levels. Three of these groups were studied in villages in the Khumbu valley at 2,650 m (Pakding), 3,440 m (Namche Bazar), and 4,243 m (Pheriche). These participants were studied at the altitude of residence. The fourth group was investigated at 1,330 m in Kathmandu. These Sherpas had been born in the Kumbu valley but resided in Kathmandu for an average of 3.5 yr (range = 0.5–12 yr). The four locations were selected for ease of access and because of the relatively equal altitude difference between them. Physical examination showed the studied Sherpas to be healthy. A systolic blood pressure above 150 mmHg and age under 18 yr and above 55 yr were exclusion criteria for the study. A group of healthy Caucasians (n = 10) was also studied in Amsterdam at sea level to document that our procedure yielded values of autoregulation that approximate published data for normal individuals (12, 37). The study was approved by the human research review board of the Academic Medical Center of the University of Amsterdam and performed in accordance with the guidelines outlined in the Declaration of Helsinki. Informed consent was obtained from all participants.

Measurements.   A blood pressure cuff (Light Monitor, Datex, Finland) was applied on the upper arm to measure MAP. This monitor was also used to measure percent oxygen saturation of arterial hemoglobin (SaO2) with fingerpulse oximetry and to measure end-tidal PCO2 (PETCO2) from a mouthpiece using side-stream sampling (200 ml/min).

Vmca was measured with a 2-MHz pulsed-wave transcranial Doppler system with online spectrum analysis (T2–64; EME). With a hand-held probe, Doppler signals from the left MCA were identified through the temporal window and obtained at a depth of 45–60 mm, corresponding to the proximal segment of the MCA. The MCA mean velocity (Vmca) is automatically calculated by the standard algorithm of the instrument for each 4-s sweep and is displayed on the apparatus. Each Vmca value, as used in the study, is then the average of four successive readings over 1–1.5 min. We analyzed the reproducibility of the velocities both at sea level and at altitude by calculating the coefficient of variation (CV) of each of four readings. The CV value was calculated from the equation CV = SD of four Vmca readings/mean value of the four readings x 100%, where SD is standard deviation. Twenty (4.4%) of a total of 474 CVs were higher than 6%, and only 7 (1.4%) were between 7.5% and 12%. Thus CV values of each of the four readings are within the CV of 6–11% as determined for intraobserver variation for measurements of Vmca (25). The reproducibility of the four readings is thus acceptable for our measurement method of Vmca.

Blood from a forearm vein was sampled to measure hematocrit (Ht) (Depex). Given Ht values (%) are expressed as the average of two measurements.

Protocol.   The subjects, who were lying comfortably in a supine position, rested at least 15 min before the start of the measurements. An intravenous needle was introduced in a forearm vein. Baseline values for MAP, Vmca, SaO2, and PETCO2 were obtained during stable hemodynamic and ventilatory conditions. Thereafter, a slow increase of MAP of ~30–35 mmHg was induced over a 20- to 30-min interval period by intravenous infusion of phenylephrine (0.02%), administered through a pump (Perfusor Secura, Braun, Germany). During this period, 5–12 paired values of MAP and Vmca were obtained in each subject (35, 38). At the end of the protocol, SaO2 and PETCO2 were measured to verify that ventilatory conditions had not changed.

To study whether the acute administration of oxygen had an effect on the CA, we repeated the study in the Sherpas in the highest village at 4,243 m (Pheriche-O2 group). Thus they were allowed to breath, with a nose clip, through a mouthpiece with the addition of oxygen (5 l/min) to the inspired air. After an adjustment period of ~15 min, the study protocol was repeated.

Autoregulation index.   Because the relation between the systemic blood pressure and CBF within the autoregulatory range is considered linear, regression analysis on the acquired blood pressure values and their corresponding Vmca values were performed to yield a regression line. When MAP1 and MAP2 are, respectively, the lowest and the highest blood pressure values as measured in each subject, then Vmca1 and Vmca2 are considered the corresponding Vmca values on the regression line.

To compare the autoregulation between groups and subjects, the autoregulatory capacity was quantified using the autoregulation index (AI) (35). AI is the percent change in estimated cerebral vascular resistance (CVRe, which is calculated as MAP/Vmca) per percent change in MAP:

Formula 1(1)
The CVRe values at the lowest and at the highest blood pressure are then, respectively,

Formula 2(2)

Full autoregulatory capacity is present when the percent change in CVRe is equal to the percent change in MAP. No change in Formula 2mca in response to an increase of MAP would result in an AI of 1.0 and implies that Formula 2mca is totally independent of MAP. A totally absent autoregulation would result in an AI of 0, and Formula 2mca changes proportionally with alterations of MAP (35, 38).

Statistical analysis.   Data are presented as means ± SD. Possible association between AI and the baseline characteristics (age, weight) in the four Sherpa groups was explored with Pearson correlation coefficient. ANOVA and Bonferroni correction for post hoc analysis and paired t-test were used where appropriate. A level of P < 0.05 was considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
No dependence was found between the AI and the studied baseline characteristics in the four Sherpa groups. There were no differences in age, weight, PETCO2, MAP, and Formula 2mca between the four Sherpa groups (Table 1). The Sherpas at 4,243 m had significantly higher Ht than the group at 1,330 m. SaO2 at 4,243 m was significantly lower than at the lower altitudes, and SaO2 at 3,440 m was lower than at 2,650 and 1,330 m. During the study protocol, mean PETCO2 values of each group remained within 0.08 kPa, and mean SaO2 values remained within 0.3% from the resting control values. During the highest phenylephrine infusion rate, MAP increases in the various groups were 31–35 mmHg (Table 2), and corresponding Formula 2mca changes showed increases in Formula 2mca that were higher in the group at 4,243 m than in all other groups (P < 0.01).


View this table:
[in this window]
[in a new window]

  		Table 1. Demographic and physiological values in Sherpas residing at four various altitude levels and in Caucasians at sea level

 

View this table:
[in this window]
[in a new window]

  		Table 2. Changes of physiological variables from baseline during maximal phenylephrine infusion and autoregulation index

 
Autoregulation curves, as calculated from the paired MAP and Formula 2mca data of each subject at the five altitude levels, are shown in Fig. 1. The mean AI of Sherpas at 4,243 m was lower than the mean AI of Sherpas who resided at the lower altitudes (P < 0.0005). The Caucasian group at sea level had an AI of 0.81.


Figure 1
View larger version (14K):
[in this window]
[in a new window]

  		Fig. 1. Individual autoregulation curves (thin lines), composed of middle cerebral artery blood flow velocity (Formula 2mca) as a function of mean arterial blood pressure (MAP) during infusion of phenylephrine in 4 Sherpa groups at various altitude levels (1,330, 2,650, 3,440, and 4,243 m) and in Caucasians at sea level. For each group, the mean autoregulatory curve has been depicted (thick lines).

 
During the administration of oxygen at 4,243 m, SaO2 increased from 88 to 98% (paired t-test; P < 0.001), PETCO2 decreased from 4.0 to 3.8 kPa (paired t-test; P = 0.01), and Formula 2mca decreased from 59 to 56 cm/s (paired t-test; P = 0.039). AI increased from 0.22 to 0.49 (paired t-test; P = 0.0082; Fig. 2).


Figure 2
View larger version (12K):
[in this window]
[in a new window]

  		Fig. 2. Individual autoregulation index ({circ}), along with mean values (bullet) and 95% confidence limits, for 4 Sherpa groups residing at various altitudes and for a Caucasian group at sea level. In the group living at 4,243 m, measurements were also made while individuals breathed a hyperoxic mixture.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The major findings of this study were that CA was severely impaired in Sherpas residing at 4,243 m, confirming reports from a previous study (17). We also found that Sherpas, residing at 1,330, 2,650, and 3,440 m, showed identical values of autoregulation, although these values were less than normally seen in healthy sea-level subjects. Our second finding is that the administration of oxygen at 4,243 m improved the CA to values that were not different from the values in Sherpas at the lower altitudes. The results of these investigations demonstrate that, from an altitude of ~4,000 m, critical changes occur in CA of high-altitude dwellers, which are reversible with the administration of oxygen.

The effect of acute hypoxia on the cerebral circulation shows invariably vasodilatation and an increase in CBF (19). With more prolonged exposure to hypoxia at altitude, the effect diminishes after 3–5 days and CBF returns to the prehypoxic CBF levels (28, 29, 32). However, Tibetan and Andean highlanders have a normal or below normal CBF (15, 26, 27, 33). This normal, sea-level CBF, despite a low arterial PO2, is probably caused by an increased blood viscosity due to the higher Ht in high-altitude residents as a result of erythropoietin upregulation (5, 27). Milledge and Sørensen (27) found that breathing 100% oxygen in natives in Cerro de Pasco decreased CBF by 18%, demonstrating no blunting of the vasodilatation reflex under lifelong hypoxia, and showed that vasodilatation by hypoxia persists after a lifetime of exposure to high altitude. Krasney et al (21), in a review, provided evidence that the primary CBF response to acute hypoxia does not adapt during lifelong hypoxia. There is thus no resetting of the CBF in the face of a continuing hypoxic stimulus for vasodilatation. Thus highlanders are left with some cerebral vasodilatation due to a low Po2 and an average sea-level CBF due to an increase in packed cell volume. The identical Formula 2mca values in our subjects at 4,243 and at 1,330 m are thus fully explained by the 25% lower Ht in the latter group.

Loss of autoregulation.   Although the nature of the autoregulatory dysfunction is unknown, our results are consistent with the idea that vasodilatation of the cerebral vessels occurring during high-altitude hypoxia at 4,243 m might be responsible for the loss of autoregulation. Mechanisms that, at sea level, produce cerebral vasodilatation have an inherent capability to impair CA. Such mechanisms include hypercapnia (13), drugs that "directly" dilate cerebral vessels such as volatile anesthetics, and severe hypoxia in animals (13, 20). Cerebral vessel dilatation probably also occurs during high-altitude hypoxia at 4,243 m. Support for cerebral vessel dilatation at high altitude is provided by a study that showed that, during acute exposure to increasing hypoxic levels, Formula 2mca increases when SaO2 drops below 90% (11). This corresponds to an arterial PO2 of 58 Torr, which is higher than conventionally reported arterial PO2 levels of 50–53 Torr, which were obtained in anesthetized dogs (24). We measured SaO2 of 88% in the Sherpas at 4,243 m, and, because Sherpas have a normal hemoglobin-oxygen dissociation curve (30), the SaO2 of 88% corresponds with an arterial PO2 of 55 Torr, which is even lower when we consider that chronic mountain dwellers have a slightly alkalotic pH, yielding a lower arterial PO2 at a given oxygen saturation through a leftward shift of the hemoglobin-oxygen dissociation curve. This effect of vasodilatation below the SaO2 level of 90% may play a role in explaining the almost total loss of CA at 4,243 m.

Hyperoxic breathing.   The underlying idea that vasodilatation of the cerebral vessels at 4,243 m as a response to the high-altitude hypoxia may account for the critically impaired autoregulation is supported by our finding of the improvement of the autoregulation during the administration of oxygen. Paulson et al. (29) found that, just as cerebral vasodilatation impairs autoregulation, cerebral vasoconstriction, as caused by oxygen replenishment, reestablishes an impaired autoregulation. During hyperoxic breathing, at least two mechanisms contribute to produce cerebral vasoconstriction. First, hyperoxia has a direct cerebral vasoconstrictive effect and produces a marked decrease in CBF at altitude, as shown in Andean high-altitude natives (26, 27, 33), as well as at sea level (9, 40). Second, hyperoxia causes an increase in minute ventilation and a decrease of PETCO2 (4). This last process is possibly initiated by increased production of reactive oxygen species during hyperoxia, which stimulate central carbon dioxide chemoreceptors to increase ventilation and is known as hyperoxic hyperventilation (7). During oxygen administration in our study, Formula 2mca decreased from 59 to 56 cm/s and PETCO2 decreased from 4.0 to 3.8 kPa. Thus it is likely that cerebral vasoconstriction occurs during hyperoxic breathing at altitude, which might improve the impaired autoregulation. We did not measure the effect of hyperoxic breathing on the autoregulation in the lower altitude regions. However, if we consider the AI values of 0.63, 0.57, and 0.57 at 1,330, 2,650, and 3,440 m, respectively, as slightly impaired compared with AI values of 0.80–0.90 in our Caucasian group at sea level and in healthy awake subjects (12, 37), hyperoxic breathing should similarly improve CA at the lower altitudes.

Physiological mechanism.   Although impairment of the CA at altitude can be, at least partially, explained by physiological mechanisms that produce cerebral vasodilatation, on the molecular level there exists a lack of contractility of the vessels that regulate CA in the brain. There should be either a surplus of vasodilator activity, such as nitric oxide (NO), or a lack of vasoconstrictors, such as endothelin-1 (1).

NO acts locally on the arteriolar smooth muscle. However, NO regulation of vessel diameter, which resides within the endothelium, is separate from the NO regulation of vessel diameter, which is dependent on the oxygen content of blood, more specifically on the red blood cells. Red blood cells are able to release NO in the presence of hypoxia far from their location of formation, and this function, mediated by S-nitrosohemoglobin, accounts for hypoxia-induced vasodilatation (34). In this respect, exhalation of NO by Tibetans living at 4,200 m is increased compared with that shown in sea-level subjects (3). Recently, it was shown that, in rat brains during permanent exposure to hypobaric hypoxia, there is a decrease of endothelin-1 production within the brain, which may help protect neurons by preventing or limiting the constriction of cerebral microvessels during hypoxia (18). Thus a surplus of NO and/or a decrease of endothelin-1 production might account for the impaired CA in the high-altitude residents.

Critique of the study.   Hypoxia can impair the autoregulation in one of two ways: it can affect either the position of the upper and/or lower limits of autoregulation (width of the autoregulatory plateau) or the gradient of the autoregulatory plateau or both. Because the maximally attained MAP did not exceed 160 mmHg in any subject, the MAP values remained within the normal autoregulatory range of ~60–160 mmHg, and we assessed the gradient of the autoregulatory plateau. However, it is possible that under the hypoxic conditions at 4,243 m the gradient of the autoregulatory plateau had been affected or that the right upper limit of the autoregulatory plateau had been shifted. On the one hand, hypoxia and vasodilatation might shift the upper limit leftward, which would cause increases in MAP beyond this limit to produce pressure passive increases in CBF. On the other hand, an increased sympathetic activity, as has been demonstrated at least in newcomers at altitude (14), might shift the upper limit rightward and thus prevent cerebral hyperperfusion. Because the raw autoregulatory curves at 4,243 m in Fig. 1A all show upward inclinations and fit a straight line, it might indicate that we assessed the gradient of the autoregulatory plateau and that the upper limit was not shifted leftward.

Employing transcranial Doppler sonography to test for "static" CA requires, under the hypoxic circumstances of high altitude, the diameter of the MCA to not change during the infusion of phenylephrine. The intravenous infusion of phenylephrine, an exogenous amine with {alpha}1-agonist properties, besides its effect of increasing MAP, may have produced vasoconstriction of the MCA. However, studies performed at sea level show a lack of vasoconstriction of cerebral blood vessels from {alpha}-adrenergic agonists (8, 10). Furthermore, in response to chronic high-altitude hypoxia, the cerebral arteries of adult sheep show decreased density of {alpha}1-adrenergic receptors (39) and decreased contractile responses to norepinephrine and other {alpha}-agonists (23, 24). Thus it is not likely that the administration of phenylephrine, as in this study, has important effects on the diameter of the MCA, which might interfere with autoregulation measurements.

In summary, the results of these investigations demonstrate that, with increasing altitudes, CA becomes increasingly impaired in Himalayan high-altitude dwellers. Furthermore, the altitude region between ~3,500 and 4,200 m is a region above which CA becomes critically impaired, and we demonstrated that increasing the SaO2 with the administration of oxygen partially improves this critically impaired autoregulation.


   FOOTNOTES
 

Address for reprint requests and other correspondence: G. F. A. Jansen, Dept. of Anesthesiology, H1-Z, Academic Medical Centre, Univ. of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands (e-mail: g.f.jansen{at}amc.uva.nl)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Andresen J, Nadeem IS, Bryan RM Jr. Endothelial influences on cerebrovascular tone. J Appl Physiol 100: 318–327, 2006.[Abstract/Free Full Text]
  2. Ainslie PN, Burgess K, Subedi P, Burgess KR. Alterations in cerebral dynamics at high altitude following partial acclimatization in humans: wakefulness and sleep. J Appl Physiol 102: 658–664, 2007.[Abstract/Free Full Text]
  3. Beall CM, Laskowsky D, Strohl KP, Soria R, Villena M, Vargas E, Alarcon AM, Gonzales C, Erzurum SC. Pulmonary nitric oxide in mountain dwellers. Nature 414: 411–412, 2001.[CrossRef][Medline]
  4. Becker H, Polo O, McNamara SG, Berthon-Jones M, Sullivan CE. Ventilatory response to isocapnic hyperoxia. J Appl Physiol 78: 696–701, 1995.[Abstract/Free Full Text]
  5. Brown MM, Wade JP, Marshall J. Fundamental importance of arterial oxygen content in the regulation of cerebral blood flow in man. Brain 108: 81–93, 1985.[Abstract/Free Full Text]
  6. Czosnyka M, Smielewski P, Piechnik S, Steiner LA, Pickard JD. Cerebral autoregulation following head injury. J Neurosurg 95: 756–763, 2001.[CrossRef][ISI][Medline]
  7. Dean JB, Mulkey DK, Henderson RA 3rd, Potter SJ, Putnam RW. Hyperoxia, reactive oxygen species, and hyperventilation: oxygen sensitivity of brain stem neurons. J Appl Physiol 96: 784–791, 2004.[Abstract/Free Full Text]
  8. Edvinsson L, Owman C. Pharmacological characterization of adrenergic alpha and beta receptors mediating the vasomotor responses of cerebral arteries in vitro. Circ Res 35: 835–849, 1974.[Abstract/Free Full Text]
  9. Floyd TF, Clark JM, Gelfand R, Detre JA, Ratcliffe S, Guvakov D, Lambertsen CJ, Eckenhoff RG. Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA. J Appl Physiol 95: 2453–2461, 2003.[Abstract/Free Full Text]
  10. Giller CA, Bowman G, Dyer H, Mootz L, Krippner W. Cerebral arterial diameters during changes in blood pressure and carbon dioxide during craniotomy. Neurosurgery 32: 737–742, 1993.[ISI][Medline]
  11. Gupta AK, Menon DK, Czosnyka M, Smielewski P, Gareth Jones J. Thresholds for hypoxic cerebral vasodilation in volunteers. Anesth Analg 85: 817–820, 1997.[Abstract]
  12. Gupta S, Heath K, Matta BF. Effect of incremental doses of sevoflurane on cerebral pressure regulation in humans. Br J Anaesth 79: 469–472, 1997.[Abstract/Free Full Text]
  13. Häggendal E, Johansson B. Effects of arterial carbon dioxide tension and oxygen saturation on cerebral blood flow autoregulation in dogs. Acta Physiol Scand 66, Suppl 258: 27–53, 1965.
  14. Hansen J, Sander M. Sympathetic neural overactivity in healthy humans after prolonged exposure to hypobaric hypoxia. J Physiol 546: 921–929, 2002.[CrossRef][ISI]
  15. Huang SY, Sun S, Droma T, Zhuang J, Tao JX, McCullough RG, McCullough RE, Micco AJ, Reeves JT, Moore LG. Internal carotid arterial flow velocity during exercise in Tibetan and Han residents of Lhasa (3,658 m). J Appl Physiol 73: 2638–2642, 1992.[Abstract/Free Full Text]
  16. Immink RV, van den Born BJH, van Montfrans GA, Koopmans RP, Karemaker JM, van Lieshout JJ. Impaired cerebral autoregulation in patients with malignant hypertension. Circulation 110: 2241–2245, 2003.[CrossRef][ISI]
  17. Jansen GFA, Krins A, Basnyat B, Bosch A, Odoom JA. Cerebral autoregulation in subjects adapted and not adapted to high altitude. Stroke 31: 2314–2318, 2000.[Abstract/Free Full Text]
  18. Kanazawa F, Nakanishi K, Osada H, Kanamaru Y, Ohrui N, Uenoyama M, Masaki Y, Kanatani Y, Hiroi S, Tominaga S, Yakata-Suzuki A, Matsuyama S, Kawai T. Expression of endothelin-1 in the brain and lung of rats exposed to permanent hypobaric hypoxia. Brain Res 1036: 145–154, 2005.[CrossRef][ISI][Medline]
  19. Kety SS, Schmidt CF. The effect of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 27: 484–492, 1948.[ISI][Medline]
  20. Kogure K, Scheinberg P, Reinmuth OM, Fujishima M, Busto R. Mechanisms of cerebral vasodilatation in hypoxia. J Appl Physiol 29: 233–229, 1970.
  21. Krasney JA, Jensen JB, Lassen NA. Cerebral blood flow does not adapt to sustained hypoxia. J Cereb Blood Flow Metab 10: 759–764, 1990.[ISI][Medline]
  22. Levine BD, Zhang R, Roach RC. Dynamic cerebral autoregulation at high altitude. Adv Exp Med Biol 474: 319–322, 1999.[ISI][Medline]
  23. Longo LD, Ueno N, Zhao Y, Pearce WJ, Zhang L. Developmental changes in {alpha}1-adrenergic receptors, IP3 responses, and NE-induced contraction in cerebral arteries. Am J Physiol Heart Circ Physiol 271: H2313–H2319, 1996.[Abstract/Free Full Text]
  24. Longo LD, Pearce WJ. High altitude, hypoxic-induced modulation of noradrenergic mediated responses in fetal and adult cerebral arteries. Comp Biochem Physiol 119A: 683–694, 1998.
  25. Maeda H, Etani H, Handa N, Tagaya M, Oku N, Kim BH, Naka M, Kinoshita N, Nukada T, Fukunaga R. A validation study on the reproducibility of transcranial Doppler velocimetry. Ultrasound Med Biol 16: 9–14, 1990.[CrossRef][ISI][Medline]
  26. Marc-Vergnes JP, Antezana G, Coudert J, Gourdin D, Durand J. Débit sanguin et métabolisme énergétique du cerveau et équilibre acido-basique du liquide céphalo-rachidien chez les résidents en altitude. J Physiol Paris 88: 633–654, 1974.
  27. Milledge JS, Sørensen SC. Cerebral arteriovenous oxygen difference in man native to high altitude. J Appl Physiol 32: 687–689, 1972.[Free Full Text]
  28. Moller K, Paulson OB, Hornbein TF, Colier WN, Paulson AS, Roach RC, Holm S, Knudsen GM. Unchanged cerebral blood flow and oxidative metabolism after acclimatisation to high altitude. J Cereb Blood Flow Metab 22: 118–126, 2002.[CrossRef][ISI][Medline]
  29. Paulson OB, Olesen J, Christensen MS. Restoration of autoregulation of cerebral blood flow by hypocapnia. Neurology 22: 286–293, 1972.[Free Full Text]
  30. Samaja M, Veicsteinas A, Cerretelli P. Oxygen affinity of blood in altitude Sherpas. J Appl Physiol 47: 337–341, 1979.[Abstract/Free Full Text]
  31. Schwarz S, Georgiadis D, Aschoff A, Schwab S. Effects of induced hypertension on intracranial pressure and flow velocities of the middle cerebral arteries in patients with large hemispheric stroke. Stroke 33: 998–1004, 2002.[Abstract/Free Full Text]
  32. Severinghaus JW, Chiodi H, Eger EI, Brandstater B, Hornbein TF. Cerebral blood flow in man at high altitude. Circ Res 19: 274–282, 1966.[Abstract/Free Full Text]
  33. Sørensen SC, Lassen NA, Severinghaus JW, Coudert J, Paz Zamora M. Cerebral glucose metabolism and cerebral blood flow in high-altitude residents. J Appl Physiol 37: 305–310, 1974.[Free Full Text]
  34. Stamler JS, Jia L, Eu JP, McMahon TJ, Demchenko IT, Bonaventura J, Gernert K, Piantadosi CA. Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276: 2034–2037, 1997.[Abstract/Free Full Text]
  35. Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell DW. Dynamic and static cerebral autoregulation during isoflurane, desflurane and propofol anesthesia. Anesthesiology 83: 66–76, 1995.[CrossRef][ISI][Medline]
  36. Sundgreen C, Larsen FS, Herzog TM, Knudsen GM, Boesgaard M, Aldershvile J. Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest. Stroke 32: 128–132, 2001.[Abstract/Free Full Text]
  37. Tibble RK, Girling KJ, Mahajan RP. A comparison of transient hyperaemic response test and static autoregulation tests to assess graded impairment in cerebral autoregulation during propofol, desflurane, and nitrous oxide anesthesia. Anesth Analg 93: 171–176, 2001.[Abstract/Free Full Text]
  38. Tiecks FP, Lam AM, Aaslid R, Newell DW. Comparison of static and dynamic autoregulation measurements. Stroke 26: 1014–1019, 1995.[Abstract/Free Full Text]
  39. Ueno N, Zhao Y, Zhang L, Longo LD. High altitude-induced changes in {alpha}1-adrenergic receptors and Ins(1,4,5)P3 responses in cerebral arteries. Am J Physiol Regul Integr Comp Physiol 272: R669–R674, 1997.[Abstract/Free Full Text]
  40. Watson NA, Beards SC, Altaf N, Kassner A, Jackson A. The effect of hyperoxia on cerebral blood flow: a study in healthy volunteers using magnetic resonance phase-contrast angiography. Eur J Anaesthesiol 17: 152–159, 2000.[CrossRef][ISI][Medline]



This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
P. N. Ainslie, S. Ogoh, K. Burgess, L. Celi, K. McGrattan, K. Peebles, C. Murrell, P. Subedi, and K. R. Burgess
Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation: alterations with hyperoxia
J Appl Physiol, February 1, 2008; 104(2): 490 - 498.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
103/2/518    most recent
01429.2006v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jansen, G. F. A.
Right arrow Articles by Ince, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jansen, G. F. A.
Right arrow Articles by Ince, C.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.