Hypothetic roles of angiogenesis, osmotic swelling and ischemia in
high altitude cerebral edema.
Severinghaus, John W.
Dept of Anesthesia and Cardiovascular Research Institute, Univ
Calif Medical School, San Francisco, CA 94143-0542
APStracts 2:0195A, 1995.
High altitude cerebral edema (HACE) has been tentatively attributed to
either cellular ion pump failure from ATP depletion or high cerebral
blood flow inducing high capillary pressure. These hypotheses are
inadequate because a) ATP decrease occurs only after anoxia has
silenced neuronal activity, b) prolonged hypercapnic hyperemia
generates only minor transcapillary protein leakage localized to the
less hyperemic brain regions. In connection with this review of HACE
and its causes, three other hypothetic mechanisms which might
contribute are presented: 1) Osmotic cell swelling: Cellular and
mitochondrial osmotic pressure may rise 30 mOsm in ischemia or anoxia
(potentially a 7-10% expansion). Smaller rises caused by hypoxia may
be significant in the closed calvarium. 2) Focal ischemia: This may
result from intracranial hypertension from hyperemia and osmotic
swelling. 3) Angiogenesis: Cellular hypoxia initially attracts and
activates macrophages which express VEGF (vascular endothelial growth
factor) and other cytokines, dissolving capillary basement membranes
and degrading extracellular matrix, resulting in capillary leakage.
In HACE, petechial hemorrhages are seen in the nerve cell layers of
the retina and similar changes have been described throughout the
brain. Evidence linking HACE to angiogenesis is that Dexamethasone,
an effective inhibitor of angiogenesis, has demonstrated unique
success in preventing and treating HACE.
Received 8 February 1995; accepted in final form 17 April 1995.
APS Manuscript Number A858-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.