Protective effects of alpha 1-antitrypsin on acute lung injury in rabbits induced by endotoxin.
OBJECTIVE
To investigate whether pretreatment with alpha(1)-antitrypsin (AAT) can attenuate acute lung injury (ALI) in rabbits induced with endotoxin.


METHODS
Thirty-two healthy adult New Zealand rabbits were anaesthetized, tracheotomized and mechanically ventilated. They were then randomly divided into four groups (n = 8): (1) Infusion of Escherichia coli endotoxin [Lipopolysaccharide (LPS) 500 microg/kg] without AAT (Group LPS). (2) Infusion of AAT 120 mg/kg at 15 minutes after LPS (Group LAV). (3) Infusion of AAT 120 mg/kg without endotoxin (Group AAT). (4) Infusion of saline 4 ml/kg as control (Group NS). Arterial blood gases, peripheral leukocyte counts and airway pressure were recorded every hour for eight hours. Physiologic intrapulmonary shunting (Qs/Qt) was measured every four hours. After eight hours, blood samples were collected for measurement of plasma concentration and activity of AAT. Then, the animals were sacrificed, and bronchoalveolar lavage fluid (BALF) was collected for measurement of concentrations of total protein (TP), interleukin-8 (IL-8), tumor necrosis factor (TNF alpha, the activities of NE and AAT, total phospholipids (TPL) and disaturated phosphatidylcholine (DSPC). In addition, the wet-to-dry lung weight ratio (W/D) was measured.


RESULTS
The infusion of endotoxin induced decreases in arterial oxygen pressure (PaO(2)), peripheral leukocyte counts, total respiratory compliance (TLC) and the increases in peak pressure (P(peak)), Qs/Qt compared with the baseline values (P < 0.05). The increased plasma concentration but reduced activity of AAT was also found in contrast to that in Group NS (P < 0.05). In the BALF, the activity of AAT, TPL, DSPC/TPL were lower than those in Group NS (P < 0.05), but the concentrations of albumin, IL-8, TNF alpha, the activity of NE and the ratio of W/D were higher than those in Group NS (P < 0.05). The pretreatment of AAT attenuated the deterioration of oxygenation, the reduction of compliance and the deterioration of other physiological and biochemical parameters mentioned above.


CONCLUSIONS
Pretreatment with AAT could attenuate endotoxin-induced lung injury in rabbits. Those beneficial effects of AAT might be due, in part, to reduction in the levels of mediators that could activate neutrophils, in addition to the direct inhibitory effect on neutrophil elastase.
Jie
Zhijun
Z
Department of Pulmonology, Zhongshan Hospital, Medical Center of Fudan University, Shanghai 200032, China. jiezj@citiz.net
Cai
Yingyun
Y
Yang
Wenlan
W
Jin
Meiling
M
Zhu
Wei
W
Zhu
Cifang
C
D000818:Animals; D004731:Endotoxins / Q000633:toxicity; D008171:Lung Diseases / Q000517:prevention & control*; D011817:Rabbits; D011897:Random Allocation; D000515:alpha 1-Antitrypsin / Q000494:pharmacology* / Q000627:therapeutic use
D004731:Endotoxins; D000515:alpha 1-Antitrypsin; C044101:endotoxin, Escherichia coli