Antithrombin III pretreatment reduces neutrophil recruitment into the lung and skeletal muscle tissues in the rat model of bilateral lower limb ischemia and reperfusion: a pilot study.
BACKGROUND
Anti-inflammatory action of Antithrombin III (AT III) is still not well understood in ischemia/reperfusion (I/R) injury. In the present study, we aimed to investigate the anti-inflammatory action of AT III on remote lung and local skeletal muscle tissue injury in a rat model of bilateral lower limb I/R model.


METHODS
Bilateral lower limb ischemia and reperfusion were produced by means of tourniquets occlusions and releases, respectively. Three groups of rats were used in this controlled study: sham group (sham, n=3) underwent 5 h of anesthesia only; control group (I/R, n=7) underwent 3 h of bilateral lower limb ischemia followed by 2 h of reperfusion; and AT III pretreated group (I/R-AT III, n=6) underwent the same procedure as the control group, but also received i.v. 250 U kg-1 AT III 30 min before ischemia induction under midazolam and fentanyl anesthesia.


RESULTS
Lung and muscle tissue accumulation of polymorphonuclear leukocytes (PMN) were assessed by measuring tissue myeloperoxidase (MPO) activity. Histopathological changes in tissues were assessed by PMN counts in the lung, and muscle tissues and by histological lung injury score. Plasma 6-keto prostaglandin F(1alpha) and tumor necrosis factor alpha levels were measured by an enzyme immunoassay technique. Myeloperoxidase activity could not be detected in the muscle tissues of all groups. The lung and muscle tissue PMN counts in the I/R group were significantly higher compared with the I/R-AT III group (P<0.05).


CONCLUSIONS
Data from the present study provides some evidence that AT III pretreatment attenuates remote lung and local skeletal muscle tissue injury caused by lower limb I/R.
Duru
S
S
Department of Anesthesiology and Reanimation, Atatürk Training and Research Hospital, Dokuz Eylül University, School of Medicine, Izmir, Turkey.
Koca
U
U
Oztekin
S
S
Olguner
C
C
Kar
A
A
Coker
C
C
Ulukuş
C
C
Taşcł
C
C
Elar
Z
Z
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000990:Antithrombin III / Q000494:pharmacology*; D004195:Disease Models, Animal; D007511:Ischemia / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D019194:Ischemic Preconditioning / Q000379:methods; D035002:Lower Extremity / Q000098:blood supply*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D000925:Anticoagulants; D014409:Tumor Necrosis Factor-alpha; D015121:6-Ketoprostaglandin F1 alpha; D000990:Antithrombin III; D009195:Peroxidase