Furrer M, Lardinois D, Thormann W, Altermatt H J, Betticher D, Triller J, Mettler D, Althaus U, Burt M E, Ris H B
Department of Thoracic and Cardiovascular Surgery, University of Berne, Switzerland.
Ann Thorac Surg. 1998 Jun;65(6):1523-8. doi: 10.1016/s0003-4975(98)00235-5.
Different modalities of cytostatic lung perfusion were compared regarding plasma and tissue drug concentrations to assess the efficacy of an endovascular blood flow occlusion technique.
A cytostatic lung perfusion study with doxorubicin hydrochloride was performed on large white pigs (n = 12). Plasma and tissue concentrations of doxorubicin were compared for isolated lung perfusion with open cannulation (ILP), blood flow occlusion perfusion with open cannulation of the pulmonary artery alone (BFO), and intravenous drug administration (i.v.). In a fourth group, thoracotomy-free BFO perfusion was performed by endovascular balloon catheterization of the pulmonary artery (endovascular BFO). The 3 animals in this group were used to compare the doxorubicin-perfused pulmonary tissue with the contralateral nonperfused lobes after 1 month.
The mean lung tissue doxorubicin concentration at the end of perfusion was 19.8 +/- 1.6 microg/g after ILP, 27.6 +/- 2.2 microg/g after BFO (p = not significant), and 3.0 +/- 0.8 microg/g after i.v. perfusion (p < 0.01). Whereas doxorubicin was not detectable in the plasma in the ILP group, concentrations ranged from not detectable to 0.44 microg/mL in the BFO group and from 0.31 to 0.84 microg/mL in the i.v. group (p < 0.05). Mean myocardial tissue concentration was not significantly different after BFO than i.v. perfusion (1.1 +/- 0.5 microg/g and 1.8 +/- 0.1 microg/g, respectively). In the endovascular BFO group, balloon-blocked pulmonary artery perfusion was successfully performed in all animals, and after 1 month, lung tissue showed no cytostatic-induced histologic changes.
Compared with ILP, BFO cytostatic lung perfusion produced an insignificantly higher lung-tissue concentration, corresponding to a sixfold to ninefold higher level than after i.v. perfusion. Plasma drug levels during BFO perfusion were lower than during i.v. perfusion. Endovascular BFO may be a promising technique for repeated cytostatic lung perfusion.
比较了不同的细胞毒性肺灌注方式,观察血浆和组织药物浓度,以评估血管内血流阻断技术的疗效。
对大型白色猪(n = 12)进行了盐酸多柔比星的细胞毒性肺灌注研究。比较了盐酸多柔比星在开放插管的离体肺灌注(ILP)、仅开放肺动脉插管的血流阻断灌注(BFO)和静脉给药(i.v.)后的血浆和组织浓度。在第四组中,通过肺动脉血管内球囊导管插入术进行无开胸的BFO灌注(血管内BFO)。该组的3只动物用于比较1个月后多柔比星灌注的肺组织与对侧未灌注叶。
灌注结束时,ILP后肺组织多柔比星平均浓度为19.8±1.6μg/g,BFO后为27.6±2.2μg/g(p =无显著性差异),静脉灌注后为3.0±0.8μg/g(p < 0.01)。ILP组血浆中未检测到多柔比星,BFO组浓度范围为未检测到至0.44μg/mL,静脉组为0.31至0.84μg/mL(p < 0.05)。BFO后心肌组织平均浓度与静脉灌注后无显著差异(分别为1.1±0.5μg/g和1.8±0.1μg/g)。在血管内BFO组中,所有动物均成功进行了球囊阻断肺动脉灌注,1个月后,肺组织未出现细胞毒性诱导的组织学变化。
与ILP相比,BFO细胞毒性肺灌注产生的肺组织浓度略高,比静脉灌注后高六至九倍。BFO灌注期间的血浆药物水平低于静脉灌注期间。血管内BFO可能是一种有前景的重复细胞毒性肺灌注技术。