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大鼠对侧肺移植后野百合碱诱导的肺血管疾病

Monocrotaline-induced pulmonary vascular disease after contralateral lung transplantation in the rat.

作者信息

Kawaguchi A T, Kawashima Y, Ishibashi-Ueda H, Mizuta T, Kitoh Y, Kunieda T

机构信息

National Cardiovascular Center, Osaka, Japan.

出版信息

J Heart Lung Transplant. 1993 Mar-Apr;12(2):325-8; discussion 328-9.

PMID:8476905
Abstract

To test a hypothesis that reduction in pulmonary perfusion pressure and flow affect underlying vascular disease, pulmonary pathology was studied in monocrotaline-treated rats undergoing single lung transplantation. Inbred rats were treated with 40 mg/kg (group T1, n = 6) and 80 mg/kg of monocrotaline (group T2, n = 9), received a left lung isograft 2 and 4 weeks after medication, and were killed 4 and 6 weeks after single lung transplantation, respectively. For each group, rats receiving the same amount of monocrotaline (M1, M2) or vehicle (N1, N2) served as controls. Monocrotaline-treated rats developed pulmonary vascular disease and right heart failure, resulting in severe exercise intolerance in M1 or death in M2 unless single lung transplantation had been carried out. At death, pulmonary blood flow was directed toward the left lung isograft, and the retained right lung received a significantly reduced fraction of cardiac output. Right to left ventricular weight ratio was significantly reduced in both groups as compared to the respective control rats, suggesting reduced perfusion pressure. Although thickness of media in small pulmonary arteries (media/radius) was normal (34% +/- 4%) in the lung isografts, it was significantly increased in the contralateral lung (group T1, 45% +/- 5%; group T2, 48% +/- 3%), which was not significantly different from that of monocrotaline-treated control rats, respectively (group M1, 47% +/- 7%; group M2, 49% +/- 6%). Although single lung transplantation reduced perfusion pressure and flow toward the monocrotaline-treated native lung, it failed to affect vascular morphology significantly.

摘要

为了验证肺动脉灌注压和血流量的降低会影响潜在血管疾病这一假设,我们对接受单肺移植的用野百合碱处理的大鼠的肺部病理进行了研究。近交系大鼠分别接受40mg/kg(T1组,n = 6)和80mg/kg的野百合碱(T2组,n = 9)处理,在用药后2周和4周接受左肺同种异体移植,并分别在单肺移植后4周和6周处死。对于每组,接受相同剂量野百合碱(M1、M2)或赋形剂(N1、N2)的大鼠作为对照。用野百合碱处理的大鼠出现了肺血管疾病和右心衰竭,导致M1组出现严重运动不耐受或M2组死亡,除非进行了单肺移植。在死亡时,肺血流流向左肺同种异体移植肺,而保留的右肺接受的心输出量比例显著降低。与各自的对照大鼠相比,两组的右心室与左心室重量比均显著降低,提示灌注压降低。尽管肺同种异体移植肺中小肺动脉的中膜厚度(中膜/半径)正常(34%±4%),但对侧肺中膜厚度显著增加(T1组,45%±5%;T2组,48%±3%),分别与用野百合碱处理的对照大鼠(M1组,47%±7%;M2组,49%±6%)无显著差异。尽管单肺移植降低了流向用野百合碱处理的天然肺的灌注压和血流量,但它未能显著影响血管形态。

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