Liver function in rats acclimatized to a simulated altitude of 5500 m.

ABSTRACT

We examined the functional and morphological characteristics of the liver in rats acclimatized to a simulated altitude of 5500 m. We examined the metabolic activity and cytoplasmic distribution of liver mitochondria and the capacity of the liver to regenerate after partial hepatectomy. Mitochondrial respiration, oxidative phosphorylation, the respiratory control ratio (RCR), and the morphological characteristics of mitochondria in liver sections were studied after 3 months acclimatization to high altitude (HA). Partial hepatectomy was performed in a subset of animals after 30 days acclimatization to 5500 m. The rate of hepatic regeneration, induction of ornithine decarboxylase and uridine diphosphate glucuronyltransferase (UGT1a1), and plasma bilirubin were measured 24, 48, 72, and 96 hours after hepatectomy. Acclimatization to 5500 m did not affect the mitochondrial respiratory capacity or oxidative phosphorylation. The RCR decreased and acid phosphatase activity increased, which suggests that there were subtle changes in mitochondrial integrity. In addition, mitochondria were distributed more homogeneously in hepatocytes. Hepatic regeneration, which was associated with 25-fold induction of the ornithine decarboxylase, did not differ between controls and the altitude-exposed animals. Plasma bilirubin levels rose markedly 24 hours after hepatectomy, but returned to control levels 48 hours after the operation in the altitude-exposed animals. Thus, the remarkable functional capacity of the liver was retained at simulated HA. Redistribution of hepatic mitochondria seems to play an important role in maintaining hepatic function despite severe cellular hypoxia.