Increase of Cerebral Blood Flow at High Altitude: Its Possible Relation to AMS N. A. Lassen Department of Clinical Physiology and Nuclear Medicine, Bispebjerg Hospital, Copenhagen NV, Denmark
Abstract
N. A. Lassen, Increase of Cerebral Blood Flow at High Altitude: Its Possible Relation to AMS. mt J Sports Med, Vol 13, Suppl 1,pp S47—S48, 1992.
CBF increases with acute hypoxia despite the
opposing vasoconstrictor effects of the drop in pCO2
is seen over days at constant altitude primarily due to increase in the hematocrit. The cerebral vasodilatation cannot explain the usual (mild) form of AMS. But it may well be involved in the pathogenesis of the rare but severe cerebral form of AMS, as prolonged increased capillary pressure in vasodilated areas could lead to vasogenic cerebral edema.
caused by hyperventilation. Maintaining normocapnla by
Key words
adding C02 the hypoxic CBF responsiveness about doubles. As we have shown recently by this test, the hypoxic
CBF response is not blunted but rather somewhat sharpened over five days at almost 4000 meters of aliitude. This, along with other evidence, shows that CBF does not in itself adapt to chronic hypoxia. Nevertheless, a decrease in CBF Tnt. J . Sports Med.
13(1992) 547—S48
GeorgThieme Verlag StuttgartNew York
Acute mountain sickness, role of cerebral vasodilatation, cerebral blood flow, high altitude, hypoxia, high altitude cerebral edema, cerebral blood flow regulation
Downloaded by: National University of Singapore. Copyrighted material.
mt. J. Sports Med. 13(1992) S47
S48 mt. S48 mt.J.J.Sports SportsMed. Med. 13(1992) 13(1992)
Niels A. Lassen
Comments on AMS
Acute hypoxia causes a sharp increase in cerebral blood flow (1). At the same time ventilation increases, so that arterial pCO2 drops. The hypocapnia constitutes a vasoconstrictory stimulus for the cerebral resistance vessels. The
full effect of acute hypoxia and CBF can therefore only be seen, if pCO2 is kept constant at its normal level, at eucapnia, by adding C02 to the inspired air. In studies of this kind in eucapnic hypoxia CBF increases by about double as much as, when when the the spontaneously spontaneously pCO2 pCO2 is is allowed allowed to to drop. drop.
We have recently studied studied the the effect effect on on CBF CBF of of
more protracted eucapnic hypoxia in human volunteers. These studies lasting 6 to 8 hours showed that CBF remained
constantly elevated throughout the study. Krasney and coworkers have carried out the same type of eucapnic hypoxic studies over four days. Again a sustained elevation of CBF was found.
In another study we assessed assessed CBF CBF by by the the transtranscranial Doppler method in human subjects (ourselves) living for five days at almost 4000 4000 meters meters of of altitude altitude on on White WhiteMounMountain in California. The studies were carried out by varying the oxygen tension at a set value of pCO2 (eucapnia). This allowed
to measure the hypoxic response quantitatively during during the the early phase of adaptation to high altitude. The results showed no dampening of the percentical increase in CBF caused by hypoxia. It can be concluded, that the cerebral circulation retains
its responsiveness to hypoxia: this regulation safeguarding
Is the increase of CBF a causative factor in acute mountain sickness. This is highly unlikely. The increase in blood flow is almost instantaneous, while AMS, more specifically the headache, sets on only after hours. Also, the acute alleviation of AMS headache by acetazolamide (Diamox) (Diarnox) is associated by a further increase in CBF, not a decrease. The same effect, a slight improvement of AMS headache, has been found by elevating pCO2 moderately, a stimulus also increasing CBF.
There is thus no evidence pointing to a role of hypoxic cerebral arteriolar dilatation in the pathogenesis of Acute Acute Mountain Mountain Sickness, Sickness, of of the the usual usual mild mild type. type. In In the the few few inindividuals that that go go on on to to develop developthe thesevere severecerebral cerebralform called dividuals form called High Altitude Cerebral Edema (HACE), the situation appears to be quite different, as will be briefly explained. In HACE the symptoms point to acute brain edema: the eye-grounds eye-grounds show show papil-edema papil-edema and and very very importantly importantly aa few few Magnetic Magnetic Resonance Resonance
Images (MRI) taken a few hours after acute descent have directly shown edema fluid in the white matter. These studies,
that we owe to Peter Hackett's group studying sick mountaineers on Mt. Logan in Alaska, show practically the same changes as seen in acute hypertensive encephalopathy, where multifocal multifocal hyperemia hyperemia is is the the suspected suspected key key pathogenetic pathogenetic mechmechanism. anism. This strengthens the theory of hypoxic cerebral cerebral vasodivasodilatation via increase in the capillary pressure causes a vasogenic cerebral edema of key genie key pathogenetic pathogenetic importance importance for forthe the development of HACE.
cerebral oxygen supply does not show any signs of adaptation (Fig. 1).
But what happens in man breathing spontaneously and climbing to high and higher altitudes. Again CBF increases despite the opposing forces of hypocapnia and of the increase in the hematocrit caused by hemoconcentration and beginning polycythemia. This was observed under field Xenon-133 conditions measuring cerebral blood flow by the Xenon-I 33 clearance clearance method in the Himalayas at 3,800 meters meters 44 days days after after leaving sea level altitude and again at 5000 meters 8 to 10 days after starting the ascent.
Therefore, it can be concluded, that the sustained and progressive hypoxia of climbing higher and higher over a few weeks to reach very high peaks is associated by a marked elevation of CBF, an elevation that the adaptive vasoconstricting mechanisms mentioned cannot fully counteract.
CO,- CB COj CB
CB Rtiv,f CB
CQ
Ititde.
— -4ypc.1 -4ypc1
3 C&
4PCOz
2 di.id.a divjd. b,, O7.
3
i-a 1-a
3:q
5
S JvL dz t Iffl.d Ag. 1 Fig.
Cerebral blood flow reactivity to C02 and hypoxia at 3800 meters of altitude.
This is the currently most favoured theory of the development of HACE. It should, however, be mentioned
that fatal cerebral accidents accidents at at extreme extreme altitude altitude may may result result from very different mechanisms. In particular cases of cerebral venous thrombosis (related to dehydration?) have been noted at autopsy. It is here assumed that the changes are not secondary (agonal) but primary (causing fatal brain lesion).
The data on CBF and cerebral edemas in High Altitude, in particular in AMS sufferers, are very incomplete.
We hope more data will be collected, so that the combined knowledge — from all body systems — can allow one to prevent
the severe often fatal AMS. No doubt bad judgement, confu-
sion/delusion/euphoria/depression/extreme weakness, dehydration, cold exposure and insomnia all contribute. But, nevertheless, a concise elucidation of the pathogenetic role of hypoxia per se versus secondary factors as brain capillary hypertension and edema is also of interest, as they may be preventable by simple means. References Kety S. S., Schmidt C. F.: The effect of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. JJClin ClinIn Invest vest27: 27:484— 484— 492, 1948. 2 Hackett P. (unpublished observations). observations).
Prof Niels A. A. Lassen, Lassen, M. M D. Dept. Dept. of of Clinical Clinical Physiology/Nuclear Physiology/Nuclear Medicine Medicine Bispebjerg Hospital Bispebjerg Bispebj erg Bakke Bakke 23 DK-2400 Copenhagen NV, Denmark
Downloaded by: National University of Singapore. Copyrighted material.
Introduction
Abstract
N. A. Lassen, Increase of Cerebral Blood Flow at High Altitude: Its Possible Relation to AMS. mt J Sports Med, Vol 13, Suppl 1,pp S47—S48, 1992.
CBF increases with acute hypoxia despite the
opposing vasoconstrictor effects of the drop in pCO2
is seen over days at constant altitude primarily due to increase in the hematocrit. The cerebral vasodilatation cannot explain the usual (mild) form of AMS. But it may well be involved in the pathogenesis of the rare but severe cerebral form of AMS, as prolonged increased capillary pressure in vasodilated areas could lead to vasogenic cerebral edema.
caused by hyperventilation. Maintaining normocapnla by
Key words
adding C02 the hypoxic CBF responsiveness about doubles. As we have shown recently by this test, the hypoxic
CBF response is not blunted but rather somewhat sharpened over five days at almost 4000 meters of aliitude. This, along with other evidence, shows that CBF does not in itself adapt to chronic hypoxia. Nevertheless, a decrease in CBF Tnt. J . Sports Med.
13(1992) 547—S48
GeorgThieme Verlag StuttgartNew York
Acute mountain sickness, role of cerebral vasodilatation, cerebral blood flow, high altitude, hypoxia, high altitude cerebral edema, cerebral blood flow regulation
Downloaded by: National University of Singapore. Copyrighted material.
mt. J. Sports Med. 13(1992) S47
S48 mt. S48 mt.J.J.Sports SportsMed. Med. 13(1992) 13(1992)
Niels A. Lassen
Comments on AMS
Acute hypoxia causes a sharp increase in cerebral blood flow (1). At the same time ventilation increases, so that arterial pCO2 drops. The hypocapnia constitutes a vasoconstrictory stimulus for the cerebral resistance vessels. The
full effect of acute hypoxia and CBF can therefore only be seen, if pCO2 is kept constant at its normal level, at eucapnia, by adding C02 to the inspired air. In studies of this kind in eucapnic hypoxia CBF increases by about double as much as, when when the the spontaneously spontaneously pCO2 pCO2 is is allowed allowed to to drop. drop.
We have recently studied studied the the effect effect on on CBF CBF of of
more protracted eucapnic hypoxia in human volunteers. These studies lasting 6 to 8 hours showed that CBF remained
constantly elevated throughout the study. Krasney and coworkers have carried out the same type of eucapnic hypoxic studies over four days. Again a sustained elevation of CBF was found.
In another study we assessed assessed CBF CBF by by the the transtranscranial Doppler method in human subjects (ourselves) living for five days at almost 4000 4000 meters meters of of altitude altitude on on White WhiteMounMountain in California. The studies were carried out by varying the oxygen tension at a set value of pCO2 (eucapnia). This allowed
to measure the hypoxic response quantitatively during during the the early phase of adaptation to high altitude. The results showed no dampening of the percentical increase in CBF caused by hypoxia. It can be concluded, that the cerebral circulation retains
its responsiveness to hypoxia: this regulation safeguarding
Is the increase of CBF a causative factor in acute mountain sickness. This is highly unlikely. The increase in blood flow is almost instantaneous, while AMS, more specifically the headache, sets on only after hours. Also, the acute alleviation of AMS headache by acetazolamide (Diamox) (Diarnox) is associated by a further increase in CBF, not a decrease. The same effect, a slight improvement of AMS headache, has been found by elevating pCO2 moderately, a stimulus also increasing CBF.
There is thus no evidence pointing to a role of hypoxic cerebral arteriolar dilatation in the pathogenesis of Acute Acute Mountain Mountain Sickness, Sickness, of of the the usual usual mild mild type. type. In In the the few few inindividuals that that go go on on to to develop developthe thesevere severecerebral cerebralform called dividuals form called High Altitude Cerebral Edema (HACE), the situation appears to be quite different, as will be briefly explained. In HACE the symptoms point to acute brain edema: the eye-grounds eye-grounds show show papil-edema papil-edema and and very very importantly importantly aa few few Magnetic Magnetic Resonance Resonance
Images (MRI) taken a few hours after acute descent have directly shown edema fluid in the white matter. These studies,
that we owe to Peter Hackett's group studying sick mountaineers on Mt. Logan in Alaska, show practically the same changes as seen in acute hypertensive encephalopathy, where multifocal multifocal hyperemia hyperemia is is the the suspected suspected key key pathogenetic pathogenetic mechmechanism. anism. This strengthens the theory of hypoxic cerebral cerebral vasodivasodilatation via increase in the capillary pressure causes a vasogenic cerebral edema of key genie key pathogenetic pathogenetic importance importance for forthe the development of HACE.
cerebral oxygen supply does not show any signs of adaptation (Fig. 1).
But what happens in man breathing spontaneously and climbing to high and higher altitudes. Again CBF increases despite the opposing forces of hypocapnia and of the increase in the hematocrit caused by hemoconcentration and beginning polycythemia. This was observed under field Xenon-133 conditions measuring cerebral blood flow by the Xenon-I 33 clearance clearance method in the Himalayas at 3,800 meters meters 44 days days after after leaving sea level altitude and again at 5000 meters 8 to 10 days after starting the ascent.
Therefore, it can be concluded, that the sustained and progressive hypoxia of climbing higher and higher over a few weeks to reach very high peaks is associated by a marked elevation of CBF, an elevation that the adaptive vasoconstricting mechanisms mentioned cannot fully counteract.
CO,- CB COj CB
CB Rtiv,f CB
CQ
Ititde.
— -4ypc.1 -4ypc1
3 C&
4PCOz
2 di.id.a divjd. b,, O7.
3
i-a 1-a
3:q
5
S JvL dz t Iffl.d Ag. 1 Fig.
Cerebral blood flow reactivity to C02 and hypoxia at 3800 meters of altitude.
This is the currently most favoured theory of the development of HACE. It should, however, be mentioned
that fatal cerebral accidents accidents at at extreme extreme altitude altitude may may result result from very different mechanisms. In particular cases of cerebral venous thrombosis (related to dehydration?) have been noted at autopsy. It is here assumed that the changes are not secondary (agonal) but primary (causing fatal brain lesion).
The data on CBF and cerebral edemas in High Altitude, in particular in AMS sufferers, are very incomplete.
We hope more data will be collected, so that the combined knowledge — from all body systems — can allow one to prevent
the severe often fatal AMS. No doubt bad judgement, confu-
sion/delusion/euphoria/depression/extreme weakness, dehydration, cold exposure and insomnia all contribute. But, nevertheless, a concise elucidation of the pathogenetic role of hypoxia per se versus secondary factors as brain capillary hypertension and edema is also of interest, as they may be preventable by simple means. References Kety S. S., Schmidt C. F.: The effect of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. JJClin ClinIn Invest vest27: 27:484— 484— 492, 1948. 2 Hackett P. (unpublished observations). observations).
Prof Niels A. A. Lassen, Lassen, M. M D. Dept. Dept. of of Clinical Clinical Physiology/Nuclear Physiology/Nuclear Medicine Medicine Bispebjerg Hospital Bispebjerg Bispebj erg Bakke Bakke 23 DK-2400 Copenhagen NV, Denmark
Downloaded by: National University of Singapore. Copyrighted material.
Introduction
