Protective effects of moderate hypothermia on phosphoenergetic metabolism in rat liver during gradual hypoxia studied by in vivo 31P nuclear magnetic resonance spectroscopy.
BACKGROUND
Hepatic hypoxia during resuscitation and other critically ill conditions is a serious cause of acute hepatic failure. Measurement of the ATP concentration is a sensitive method to evaluate the extent of hypoxic damage in the liver. Hypothermia has been shown to attenuate organ injury in hypoxia. Our aim was to evaluate the effects of moderate hypothermia on the hepatic energy metabolism in rats during gradual hypoxia using (31)P nuclear magnetic resonance (NMR) spectroscopy.


METHODS
The rats were divided into two groups: a normothermia group (n = 8, rectal temperature at 37-37.5 degrees C) and a hypothermia group (n = 8, rectal temperature at 30-32 degrees C). The fraction of inhaled oxygen (F(I)O(2)) was reduced gradually (0.5, 0.2, 0.15, 0.125, 0.1, 1.0) and rectal temperature was regulated using a water perfusion mat under the rat body. Phosphoenergetic metabolism of the liver was evaluated from the changes in peak areas of beta-adenosine triphosphate (ATP) and inorganic phosphate (P(i)) in (31)P NMR spectra. Intracellular pH (pH(i)) was calculated from the chemical shifts between P(i) and alpha-ATP peaks.


RESULTS
In the normothermia group, beta-ATP decreased markedly and P(i) increased during hypoxia, while in the hypothermia group, both beta-ATP and P(i) changed only slightly from the initial state during hypoxia. During hypoxia, the minimal changes in beta-ATP were 18% and 80%, and the maximal changes in P(i) were 270% and 160% in the normothermia and hypothermia groups, respectively. Significant difference between the two groups was observed during hypoxia. The recoveries of beta-ATP and P(i) were more complete in the hypothermia group. The decrease in pH(i) during hypoxia was less in the hypothermia group.


CONCLUSIONS
During gradual hypoxia, beta-ATP decreased, P(i) increased, and pH(i) decreased in the rat liver, depending on the oxygen concentration. These changes were more prominent in the NT group than in the HT group. We conclude that moderate hypothermia effectively protects high energy phosphoenergetic metabolites in rat liver during gradual hypoxia as compared to normothermia.
Takahashi
Kan
K
Department of Intensive Care, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga 520-2192, Japan. kan@belle.shiga-med.ac.jp
Morikawa
Shigehiro
S
Inubushi
Toshiro
T
Nosaka
Shuichi
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D004734:Energy Metabolism; D007036:Hypothermia, Induced; D000860:Hypoxia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D010758:Phosphorus; D051381:Rats; D017208:Rats, Wistar
D010710:Phosphates; D010758:Phosphorus; D009320:Atrial Natriuretic Factor