Hypoxic and ischemic hypoxia exacerbate brain injury associated with metabolic encephalopathy in laboratory animals.
Hypoxemia is a major comorbid factor for permanent brain damage in several metabolic encephalopathies. To determine whether hypoxia impairs brain adaptation to hyponatremia, worsening brain edema, we performed in vitro and in vivo studies in cats and rats with hyponatremia plus either ischemic or hypoxic hypoxia. Mortality with hypoxic hypoxia was 0%; with hyponatremia, 22%; and with hyponatremia+hypoxia, 100%. Hyponatremia in cats produced brain edema, with a compensatory decrease of brain sodium. Ischemic hypoxia also resulted in brain edema, but with elevation of brain sodium. However, when ischemic hypoxia was superimposed upon hyponatremia, there was elevation of brain sodium with further elevation of water. Outward sodium transport in cat cerebral cortex synaptosomes was measured via three major pathways through which brain osmolality can be decreased. After hyponatremia, sodium transport was significantly altered such that brain cell osmolality would decrease: 44% increase in Na(+)-K(+)-ATPase transport activity (ouabain inhibitable); 26% decrease in amiloride-sensitive sodium uptake. The change in veratridine-stimulated sodium uptake was not significant (P > 0.05). When ischemic hypoxia was superimposed upon hyponatremia, all of the cerebral adaptive changes induced by hyponatremia alone were eliminated. Thus, hypoxia combined with hyponatremia produces a major increase in brain edema and mortality, probably by eliminating the compensatory mechanisms of sodium transport initiated by hyponatremia that tend to minimize brain swelling.
Vexler
Z S
ZS
Neuroradiology Section, University of California at San Francisco 94143.
Ayus
J C
JC
Roberts
T P
TP
Fraser
C L
CL
Kucharczyk
J
J
Arieff
A I
AI
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000830:Animals, Laboratory; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001925:Brain Damage, Chronic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002415:Cats; D005260:Female; D007010:Hyponatremia / Q000473:pathology / Q000503:physiopathology*; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D000584:Amiloride; D012964:Sodium