Effect of chronic methylene blue administration on hypoxemia in rats with common bile duct ligation.
OBJECTIVE
Acute administration of methylene blue (MB) can reverse hypoxemia in patients with hepatopulmonary syndrome (HPS). We evaluated the effect of chronic MB administration in common bile duct-ligated rats, which develop HPS by 5 weeks after surgery.


METHODS
A total of 96 Sprague-Dawley rats were used, including 63 rats with common bile duct ligation (CBDL), 22 sham-operated rats and 11 normal control rats. MB (6 mg/kg) was injected s.c. once a day for 4 weeks. Evaluation of hemodynamics and intrapulmonary vascular dilatation (IPVD), as well as blood sampling for arterial blood gas analysis, were done under conscious and unrestrained conditions. Hemodynamics were assessed by the reference sample method using (141)Ce-microspheres (15 microm in diameter), and IPVD was also determined by i.v. injection of these microspheres. Histological examination of the lungs was done with hematoxylin-eosin staining and immunohistochemical staining for von Willebrand factor or vascular endothelial growth factor.


RESULTS
Both the arterial oxygen tension and alveolar-arterial oxygen difference were significantly improved in MB-treated CBDL rats. The hyperdynamic circulation and splanchnic hyperemia seen in untreated CBDL rats were also alleviated by MB treatment. However, IPVD was not affected by MB. Histological examination of the lungs indicated that MB treatment reduced the proliferation of alveolar capillary vessels and angiogenesis, leading to improvement of arterial dysoxygenation. Hepatic synthetic and detoxification functions, as well as renal function, were not altered by MB treatment.


CONCLUSIONS
Methylene blue may be a candidate treatment for HPS that does not cause deterioration of hepatic or renal function.
Miyamoto
Akiko
A
Division of Cardiology, Hepatology, Geriatrics and Integrated Medicine, Department of Internal Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Katsuta
Yasumi
Y
Zhang
Xue-Jun
XJ
Li
Hong-Li
HL
Ohsuga
Masaru
M
Komeichi
Hirokazu
H
Shimizu
Shuji
S
Akimoto
Toshio
T
Mizuno
Kyoichi
K