Arterial hypoxemia and intrapulmonary vasodilatation in rat models of portal hypertension.
BACKGROUND
Rats with chronic bile duct ligation (CBDL) and portal vein ligation (PVL) are used as models of portal hypertension. CBDL rats show hypoxemia with intrapulmonary vasodilatation (IPVD), and are recognized as a model of hepatopulmonary syndrome (HPS), while PVL rats are normoxemic. We investigated the differences in arterial oxygenation between these models, and the key factors leading to HPS.


METHODS
Forty-eight Sprague-Dawley rats were prepared as CBDL or PVL models, or as Sham rats. Arterial oxygenation, hemodynamics (reference sample method), and IPVD were simultaneously evaluated in conscious and unrestrained animals, using (141)Ce- or (113)Sn-labeled microspheres (15 microm in diameter), respectively. Endothelin-1 (ET-1) and nitrate/nitrite (end products of nitric oxide; NOx) production by the lung tissue (increment across the lungs) was also determined.


RESULTS
The extent of IPVD was similar in both models, but hypoxemia was only observed in CBDL rats. The ET-1 level and the increment in NOx were significantly increased in CBDL rats, and the increment was directly correlated with impairment of oxygenation. Blood flow through the bronchial arteries (anatomical shunting) was increased in CBDL rats, reaching more than three times the level in PVL rats or Sham rats.


CONCLUSIONS
These results support the hypothesis that NO derived from the lung tissues contributes to hypoxemia, and IPVD appears to be a prerequisite for impaired oxygenation. The considerable increase of anatomical shunting may potentially contribute to impaired oxygenation in CBDL rats.
Katsuta
Yasumi
Y
First Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
Zhang
Xue-Jun
XJ
Ohsuga
Masaru
M
Akimoto
Toshio
T
Komeichi
Hirokazu
H
Shimizu
Shuji
S
Kato
Yoshihito
Y
Miyamoto
Akiko
A
Satomura
Katsuaki
K
Takano
Teruo
T
D000818:Animals; D001158:Arteries; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis; D020065:Hepatopulmonary Syndrome / Q000503:physiopathology*; D006975:Hypertension, Portal / Q000503:physiopathology*; D000860:Hypoxia / Q000209:etiology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008863:Microspheres; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000502:physiology*
D019332:Endothelin-1; D009566:Nitrates; D009573:Nitrites; D010100:Oxygen