SECRETORY LEUKOPROTEASE INHIBITOR ATTENUATES LUNG INJURY-INDUCED BY CONTINUOUS AIR EMBOLIZATION INTO SHEEP

被引:5
作者
GOSSAGE, JR
PERKETT, EA
DAVIDSON, JM
STARCHER, BC
CARMICHAEL, D
BRIGHAM, KL
MEYRICK, B
机构
[1] VANDERBILT UNIV,SCH MED,CTR LUNG RES,DEPT MED,DIV PULM & CRIT CARE MED,NASHVILLE,TN 37232
[2] VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37232
[3] VANDERBILT UNIV,SCH MED,DEPT PATHOL,NASHVILLE,TN 37232
[4] VET ADM MED CTR,DEPT MED,NASHVILLE,TN 37232
[5] VET ADM MED CTR,DEPT PATHOL,NASHVILLE,TN 37232
[6] UNIV TEXAS,CTR HLTH,DEPT BIOCHEM,TYLER,TX 75710
关键词
ELASTASE INHIBITOR; CHRONIC PULMONARY HYPERTENSION; ELASTIN; NEUTROPHIL ELASTASE; AEROSOL; LUNG LYMPH;
D O I
10.1152/jappl.1995.79.4.1163
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Continuous air embolization (CAE) into the pulmonary arterial circulation of sheep results in functional and structural changes of chronic pulmonary hypertension. Release of elastin peptides into lung lymph during CAE and attenuation of CAE-induced pulmonary hypertension by neutrophil depletion suggest that neutrophil elastase may contribute to these changes. To investigate this notion, we treated awake sheep with a potent neutrophil elastase inhibitor, recombinant secretory leukoprotease inhibitor (SLPI) (100 mg/day by aerosol), during 12 days of CAE (CAE + SLPI; n = 7). Controls included sheep receiving CAE + vehicle (VEH) (n = 6), VEH alone (n = 3), and SLPI alone (n = 3). SLPI significantly attenuated the CAE-induced increases in lung lymph flow (day 8; 2.3 +/- 0.5 vs. 5.6 +/- 1.7 ml/15 min), protein clearance (day 8; 1.36 +/- 0.32 vs. 3.08 +/- 0.84 ml/15 min), and elastin peptide concentration (day 8; 243 +/- 41 vs. 398 +/- 44 ng/ml). SLPI delayed the onset of sustained pulmonary hypertension from day 8 to day 12. Both CAE groups showed similar structural changes in the pulmonary arteries. SLPI was well tolerated in control sheep and did not affect hemodynamics or structure. We conclude that serine proteases may contribute to the early initiation of chronic pulmonary hypertension but do not play a striking role in its eventual development.
引用
收藏
页码:1163 / 1172
页数:10
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