Attenuation of acute lung injury following lower limb ischemia/reperfusion: the pharmacological approach.
OBJECTIVE
The purpose of this study was to examine the effects of N-acetylcysteine (NAC), calcium dobesilate (DOBE) and aprotinin on the amelioration of lung damage following ischemia/reperfusion injury in a rat hind limb model. A well known antioxidant dimethyl-sulfoxide (DMSO) was also tested for comparison.


METHODS
Ischemia was induced in the lower limb for 4 h by vascular clamping and followed by 1 h of reperfusion. Lung injury was evaluated in 5 groups as a saline (control), DMSO, NAC, DOBE and aprotinin group. Plasma creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS) as well as lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. P<0.005 was considered statistically significant.


RESULTS
Plasma TBARS values were found to be significantly lower in the DMSO (P<0.005), NAC (P<0.005) and aprotinin (P<0.005) groups compared to the control group. Lung TBARS values were significantly lower in the DMSO, NAC, DOBE and aprotinin groups compared to the control group (P<0.001, P<0.001, P<0.001). Also in the aprotinin group lung TBARS values were found to be significantly lower compared to DMSO (P<0.001), NAC (P<0.001) and DOBE (P<0.001) groups. Histological examination showed less prominent peribronchial leukostasis (P<0.005) and interstitial leukostasis (P<0.005) in all drug groups compared to the control group.


CONCLUSIONS
These observations indicate that DOBE and NAC, which are known to have antioxidant properties and aprotinin, a serine proteinase inhibitor, acted effectively on the prevention of lung injury in a rat hind limb ischemia/reperfusion model. The reason why aprotinin exerts a more protective effect than the other drugs is not clear, however, its clinical use may have the dual advantage of hemostasis and lung protection in surgical practice.
Koksal
C
C
Department of Cardiovascular Surgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. cengizkoksal@hotmail.com
Bozkurt
A K
AK
Ustundag
N
N
Konukoglu
D
D
Musellim
B
B
Sirin
G
G
Cortelekoglu
T
T
Sayin
A G
AG
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002123:Calcium Dobesilate / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006490:Hemostatics / Q000627:therapeutic use; D007770:L-Lactate Dehydrogenase / Q000097:blood; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016896:Treatment Outcome
D015415:Biomarkers; D016166:Free Radical Scavengers; D006490:Hemostatics; D017392:Thiobarbituric Acid Reactive Substances; D002123:Calcium Dobesilate; D007611:Aprotinin; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D000111:Acetylcysteine