Effects of activated protein C on coagulation and fibrinolysis in rabbits with endotoxin induced acute lung injury / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 2561-2565, 2008.
Article
in English
| WPRIM
| ID: wpr-265896
ABSTRACT
<p><b>BACKGROUND</b>Sepsis induced acute lung injury (ALI) as a common syndrome in clinical practice has a high mortality. Recombinant human activated protein C (APC) can significantly reduce the mortality of patients with severe sepsis. Several studies have implicated that APC may be protective in ALI.</p><p><b>METHODS</b>Twenty-one rabbits were operatively prepared and randomly divided into sham, control, or APC groups (n = 7 in each group). After a tracheotomy had been performed, ALI was produced in the control and APC groups by infusion of Escherichia coli endotoxin 100 microg/kg per hour intravenously for 1 hour. The sham group received only the vehicle, infusion of 20 ml of 0.9% saline. The rabbits were studied under anesthesia for 6 hours and were ventilated with 40% oxygen. Bovine APC (25 microg x kg(-1) x h(-1)) was intravenously administered. The infusion was initiated half an hour post-injury and lasted for 4 hours. The animals were resuscitated with Ringer's lactate solution.</p><p><b>RESULTS</b>In comparison with nontreatment in the control group, the infusion of APC significantly reduced the increase of thrombomodulin level (TM; control group was (0.68 +/- 0.06) ng/ml, vs APC group of (0.62 +/- 0.07) ng/ml at 6 hours, P < 0.05), and significantly attenuated the fall in protein S (PS; control group was (2.32 +/- 0.03) microg/ml at 2 hours, (2.24 +/- 0.06) microg/ml at 4 hours and (2.21 +/- 0.09) microg/ml at 6 hours, vs APC group (2.46 +/- 0.04) microg/ml at 2 hours, (2.40 +/- 0.05) microg/ml at 4 hours and (2.39 +/- 0.07) microg/ml at 6 hours, P < 0.01). In addition, APC limited the increase in plasminogen activator inhibitor-1 (PAI-1) both in plasma (control group was (0.68 +/- 0.12) ng/ml at 1 hour, (0.84 +/- 0.06) ng/ml at 2 hours, (0.87 +/- 0.08) ng/ml at 4 hours and (0.91 +/- 0.05) ng/ml at 6 hours, vs APC group (0.42 +/- 0.16) ng/ml at 1 hour, (0.43 +/- 0.04) ng/ml at 2 hours, (0.45 +/- 0.09) ng/ml at 4 hours and (0.45 +/- 0.14) ng/ml at 6 hours, P < 0.01) and in bronchoalveolar lavage fluid (at 6 hours sham, (1.05 +/- 0.05) ng/ml; control, (1.13 +/- 0.06) ng/ml; APC, (1.06 +/- 0.06) ng/ml; P < 0.05). However, APC failed to prevent the decrease in PaO(2)/FiO(2) ratio. APC-treated rabbits showed no significant difference in platelet count and antithrombin but exhibited less D-dimer production than did the controls. Moreover, APC limited the histopathological score of lung injury (2.6 +/- 0.8 in control, vs 1.4 +/- 0.6 in APC group, P < 0.01).</p><p><b>CONCLUSION</b>Anti-coagulation and pro-fibrinolysis activity may be two of the possible mechanisms by which activated protein C attenuated endotoxin-induced ALI.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Blood
/
Blood Coagulation
/
Blood Pressure
/
Protein C
/
Random Allocation
/
Antithrombin III
/
Protein S
/
Plasminogen Activator Inhibitor 1
/
Thrombomodulin
Limits:
Animals
Language:
English
Journal:
Chinese Medical Journal
Year:
2008
Type:
Article
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