Pitavastatin prevents intestinal ischemia/reperfusion-induced bacterial translocation and lung injury in atherosclerotic rats with hypoadiponectinemia.
BACKGROUND
Atherosclerosis with hypoadiponectinemia can be further aggravated by intestinal ischemia/reperfusion (II/R)-induced injuries, such as bacterial translocation and lung injury. We investigated the effect of statin administration on the risk of II/R-induced injury in atherosclerotic rats with hypoadiponectinemia.


METHODS
Wistar rats were divided into 4 groups: (1) the Normal group (normal diet), (2) the Chol group (2% high cholesterol diet), (3) the St-1w group, and (4) the St-2w group (Chol group plus pitavastatin administration for 1 or 2 weeks, respectively). The serum concentrations of lipids and adiponectin were measured preoperatively. After midline laparotomy (time, T0), the superior mesenteric artery was occluded with a microvascular clamp for 30 min, followed by 360 min of reperfusion (T1). Intestinal and lung nitric oxide (NO) concentrations were measured. Intestinal injury was assessed by microcirculatory flow, histology, and permeability. Bacterial translocation was assessed by analysis of serum peptidoglycan concentration. Lung injury was assessed by histologic examination, pulmonary permeability index, and wet/dry lung weight ratio.


RESULTS
The 2-week administration of statins with high-cholesterol feeding (St-2w group) improved hypoadiponectinemia to levels similar to those of the Normal group. Intestinal and lung NO concentrations were significantly lower at T1 in the Normal and St-2w groups than in the Chol group. Statin administration improved poor recovery of intestinal microcirculatory flow in the Chol group. At T1, intestinal and lung injuries were significantly aggravated and serum peptidoglycan concentration was significantly elevated in the Chol group compared with the Normal and St-2w groups. The 1-week administration of statins had no significant influence on serum adiponectin levels, tissue NO concentration, or tissue injury.


CONCLUSIONS
Administration of pitavastatin reduces the risk of II/R-induced injury in atherosclerotic rats with hypoadiponectinemia by improving hypoadiponectinemia and inhibiting inducible NO synthase-produced NO. Furthermore, preoperative improvement of hypoadiponectinemia may be important as an index of the protective effect of pitavastatin for II/R-induced injury in atherosclerotic rats with hypoadiponectinemia.
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Japan. hinakaga@m.ehime-u.ac.jp
Hiromichi
H
Nakagawa
Nobuo
N
Tsunooka
Yuji
Y
Yamamoto
Motohira
M
Yoshida
Tatsuhiro
T
Nakata
Kanji
K
Kawachi
D052242:Adiponectin / Q000097:blood; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D018988:Bacterial Translocation; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007410:Intestinal Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D055370:Lung Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control*
D052242:Adiponectin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010457:Peptidoglycan; D011804:Quinolines; D009569:Nitric Oxide; C108475:pitavastatin