INCREASED PULMONARY VASCULAR-PERMEABILITY IN RATS WITH BILIARY-CIRRHOSIS - ROLE OF THROMBOXANE-A2

被引:33
作者
CHANG, SW
OHARA, N
机构
[1] DENVER VET ADM MED CTR,MED SERV,DENVER,CO 80220
[2] DENVER VET ADM MED CTR,RES SERV,DENVER,CO 80220
[3] NORTHWESTERN UNIV,SCH MED,DEPT MED,CHICAGO,IL 60611
[4] LAKESIDE VET ADM MED CTR,CHICAGO,IL 60611
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1993年 / 264卷 / 03期
关键词
LIVER CIRRHOSIS; PULMONARY CIRCULATION; EICOSANOIDS; BILE DUCT LIGATION; DAZOXIBEN; WEB-2086; PULMONARY INTRAVASCULAR MACROPHAGE;
D O I
10.1152/ajplung.1993.264.3.L245
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Rats with liver cirrhosis exhibit arterial hypoxemia and loss of hypoxic pulmonary vasoconstriction similar to some patients with end-stage liver disease. We hypothesized that the pulmonary circulatory dysfunction in cirrhosis results from vascular endothelial cell injury and interstitial lung edema. To investigate this hypothesis, we compared the extravascular lung albumin leak, lung ultrastructural changes, and tissue eicosanoid levels in control and cirrhotic rats. In comparison to sham-operated controls, rats with biliary cirrhosis, 6 wk after ligation of the common bile duct, had increased lung albumin leak index (1.46 +/- 0.12 vs. 0.80 +/- 0.04, P < 0.001) and bloodless lung wet-to-dry weight ratio (4.94 +/ 0.05 vs. 4.78 +/- 0.03, P < 0.05). Electron-microscopic sections of lungs from cirrhotic rats demonstrated infiltration with intravascular macrophage-like cells, endothelial cell injury, and interstitial edema. In addition, lung tissue thromboxane B2 was significantly increased in cirrhotic rats, and pretreatment with a thromboxane synthase inhibitor, dazoxiben, reduced lung thromboxane B2 level and attenuated extravascular lung albumin leak (control 1.03 +/- 0.07, cirrhotic 2.29 +/- 0.06, cirrhotic plus dazoxiben, 1.57 +/- 0.17). In contrast, WEB 2086, a platelet-activating factor antagonist, had no effect on lung albumin leak. We conclude that pulmonary vascular permeability is increased in rats with biliary cirrhosis and that thromboxane A2 contributes to the pulmonary circulatory abnormalities in cirrhosis.
引用
收藏
页码:L245 / L252
页数:8
相关论文
共 39 条
[1]  
Arita A, 1985, Nihon Geka Gakkai Zasshi, V86, P1517
[2]   PULMONARY INTRAVASCULAR MACROPHAGES METABOLIZE ARACHIDONIC-ACID INVITRO - COMPARISON WITH ALVEOLAR MACROPHAGES [J].
BERTRAM, TA ;
OVERBY, LH ;
DANILOWICZ, R ;
ELING, TE ;
BRODY, AR .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1988, 138 (04) :936-944
[3]   INCREASED LEVELS OF PLATELET-ACTIVATING-FACTOR IN BLOOD FROM PATIENTS WITH CIRRHOSIS OF THE LIVER [J].
CARAMELO, C ;
FERNANDEZGALLARDO, S ;
SANTOS, JC ;
INARREA, P ;
SANCHEZCRESPO, M ;
LOPEZNOVOA, JM ;
HERNANDO, L .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1987, 17 (01) :7-11
[4]  
CASALSSTENZEL J, 1987, J PHARMACOL EXP THER, V241, P974
[5]  
CHANG S, 1990, American Review of Respiratory Disease, V141, pA644
[6]   BENEFICIAL EFFECT OF A PLATELET-ACTIVATING FACTOR ANTAGONIST, WEB-2086, ON ENDOTOXIN-INDUCED LUNG INJURY [J].
CHANG, SW ;
FERNYAK, S ;
VOELKEL, NF .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (01) :H153-H158
[7]   PULMONARY CIRCULATORY DYSFUNCTION IN RATS WITH BILIARY-CIRRHOSIS - AN ANIMAL-MODEL OF THE HEPATOPULMONARY SYNDROME [J].
CHANG, SW ;
OHARA, N .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1992, 145 (04) :798-805
[8]   ENDOTOXIN-INDUCED LUNG INJURY IN RATS - ROLE OF EICOSANOIDS [J].
CHANG, SW ;
WESTCOTT, JY ;
PICKETT, WC ;
MURPHY, RC ;
VOELKEL, NF .
JOURNAL OF APPLIED PHYSIOLOGY, 1989, 66 (05) :2407-2418
[9]   PLATELET-ACTIVATING-FACTOR MEDIATES HEMODYNAMIC-CHANGES AND LUNG INJURY IN ENDOTOXIN-TREATED RATS [J].
CHANG, SW ;
FEDDERSEN, CO ;
HENSON, PM ;
VOELKEL, NF .
JOURNAL OF CLINICAL INVESTIGATION, 1987, 79 (05) :1498-1509
[10]   FAILURE OF HYPOXIC PULMONARY VASOCONSTRICTION IN PATIENTS WITH LIVER CIRRHOSIS [J].
DAOUD, FS ;
SCHAEFER, JW ;
REEVES, JT .
JOURNAL OF CLINICAL INVESTIGATION, 1972, 51 (05) :1076-&