title: Changes of hepatic sinusoids in experimental septicemia of rats are correlated with the production of nitrogen monoxide. A morphometrical and immunohistochemical study.
abstract: OBJECTIVE
  Two types of experimental septic models were prepared to morphologically and histometrically analyze the changes in the hepatic sinusoid. Furthermore, the local expression of nitrogen monoxide synthetase was analyzed by immunohistochemical and immune electron microscopical studies for the purpose of investigating the involvement of nitrogen monoxide in these changes.
  
  
  METHODS
  Using Sprague-Dawley strain male rats, two types of experimental septic models were prepared. These were a bacterial peritonitis model induced by a cecal ligation and puncture method, and a peritonitis model after intraperitoneal administration of endotoxin at 10 mg/kg. Serum alanine aminotransferase and endotoxin were measured in due order. The liver tissues were sampled and examined by usual light microscopical and electron microscopical analyses. The sites of the portal and central vein regions were randomly selected, and the sinusoidal cavity/liver volume ratio was estimated by the point counting method under high magnification. In addition, the expressions of nitrogen monoxide synthetase were investigated in the collected samples of the liver, lung and aortic wall.
  
  
  RESULTS
  According to the histometrical analysis of the sinusoid, the sinusoidal cavity volume ratio at 6 hours after the onset increased from 0.0690 +/- 0.0147 to 0.089 +/- 0.004 in the central vein region. The ratio rapidly increased from 0.058 +/- 0.009 to 0.093 +/- 0.008 in the portal region from 6 to 12 hours after the onset. The values of serum alanine aminotransferase and endotoxin were significantly increased from 6 to 12 hours after the onset of peritonitis. The inducible nitrogen monoxide synthetase was observed in the alveolar macrophages, monocytes, and hepatic Kupffer cells from 6 to 12 hours after the onset of peritonitis.
  
  
  CONCLUSIONS
  These results demonstrated that the sinusoidal cavity became dilated in the sepsis model and at the same time nitrogen monoxide synthetase was expressed in the sinusoidal wall-composing cells. There is a possibility that the action of nitrogen monoxide is involved in the changes in the volume of the sinusoidal cavity, suggesting the involvement of nitrogen monoxide derived from sinusoidal wall-composing cells in the hepatic dysfunction caused by sepsis in addition to nitrogen monoxide generation from Kupffer cells.
authors.affiliation: Department of Surgery, Division of Gastroenterological Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574 Sendai, Miyagi, Japan.
authors.forename: Kojin
authors.initials: K
authors.lastname: Endo
authors.forename: Masanori
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tohru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.forename: Hajime
authors.initials: H
authors.lastname: Iwasashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Seiki
authors.initials: S
authors.lastname: Matsuno
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D019446:Endotoxemia; D004731:Endotoxins / Q000008:administration & dosage / Q000097:blood; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D023421:Models, Animal; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D010538:Peritonitis; D011183:Postoperative Complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000209:etiology / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000410:Alanine Transaminase