Ischemic preconditioning attenuates the lipid peroxidation and remote lung injury in the rat model of unilateral lower limb ischemia reperfusion.

BACKGROUND: Ischemia and reperfusion of the skeletal muscle tissue may cause remote lung injury. We aimed to evaluate the protective effect of ischemic preconditioning (IP) on the lung during unilateral lower limb ischemia reperfusion (IR). METHODS: Four groups of rats were used in this study: (i) the sham group (sham, n = 6) served as time controls, they remained anesthetized for the whole duration of the study; (ii) the ischemia and reperfusion group (IR, n = 10) underwent 4 h of left lower limb ischemia followed by 2 h of reperfusion; (iii) the ischemic preconditioning group (IP, n = 10), the left lower limbs of rats were exposed to three cycles of IP (10 min of ischemia followed by 10 min of reperfusion); and (iv) the ischemic preconditioning plus ischemia reperfusion group (IP/IR, n = 10) underwent IP followed by IR as in the IP and IR groups. Plasma and tissue samples were taken at the end of the study period for determination of lung tissue myeloperoxidase activity (MPO) and polymorphonuclear leukocyte count (PMNL), histological lung injury score and plasma thiobarbituric acid reactive substances (TBARS) level. RESULTS: PMNL count and MPO activity in the lung tissue, and plasma TBARS level were higher in the IR group compared with other groups while there were no differences between the sham and the IP and between the sham and the IP/IR groups. Histological lung injury score was higher in the IR group than in the IP/IR and sham groups. The plasma TBARS level in the IP group was significantly lower than in the IP/IR group. CONCLUSION: IP pretreatment reduces lipid peroxidation and lung injury caused by lower limb IR.

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. MEASUREMENTS AND 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.

Antithrombin III pretreatment reduces neutrophil recruitment into the lung in a rat model of abdominal sepsis.

BACKGROUND: Antithrombin III (AT III) is a serine protease inhibitor and the mechanism of its anti-inflammatory action is still not understood. In the present study, we aimed to investigate the anti-inflammatory action of AT III on lung injury in a rat model of sepsis. METHODS: Three groups of animals were used in this controlled study: the sham-operated group (sham, n = 3) which only underwent a laparotomy; the control group (control, n = 7) which underwent cecal ligation and perforation (CLP); and the AT III-treated group (AT III, n = 6) which underwent CLP and received intravenous (i.v.) 250 U/kg AT III 30 min before induction of sepsis. Rats were killed 24 h after induction of sepsis by needle aspiration of the right ventricle after a sternotomy, and the lungs and trachea were removed en bloc under ether anesthesia. RESULTS: Pulmonary accumulation of polymorphonuclear leukocytes (PMN) was assessed by measuring lung tissue myeloperoxidase (MPO) activity. Lipid peroxidation in lung tissue was assessed by tissue thiobarbituric acid reactive substance (TBARS) levels. The plasma prostacyclin level was assessed by the plasma 6-keto prostaglandin F(1alpha)(6-keto-PGF(1alpha)) level, which is a stable derivative of prostacyclin. Histopathological changes in lung tissue were assessed by PMN count in the capillaries and alveolar spaces. The lung tissue TBARS level, MPO activity and PMN count in the control group were significantly higher than in the AT III group (P < 0.05). The change in plasma 6-keto-PGF(1alpha) level in the AT III group was insignificant compared with the control group (P = 0.15). CONCLUSIONS: AT III prevented pulmonary infiltration of PMN and subsequent injury by the endothelial release of prostacyclin in CLP-induced sepsis.