Linder A, Friedel G, Fritz P, Kivistö K T, McClellan M, Toomes H
Department of Thoracic Surgery, Schillerhöhe Hospital, Gerlingen, Germany.
Thorac Cardiovasc Surg. 1996 Jun;44(3):140-6. doi: 10.1055/s-2007-1012003.
An ex-vivo isolated, perfused, and ventilated human lung (IPHL) model is well suited for many kinds of physiological, pharmacological, and surgical studies, when the physiological and biochemical conditions in the lung can be maintained near to those in vivo. The aim of this work was to develop such a model. The lung preparations used were available after resection because of bronchial carcinoma. Since the tumor remains intact in these anatomical preparations, this model is particularly suitable for investigation of the pharmacokinetics and effects of anticancer agents. Carrying out a series of 52 IPHL experiments (with 11 whole-lung preparations and 41 lobe preparations), we have established an IPHL model which allows extracorporeal perfusion and ventilation of the resected lungs in physiological conditions for 2-3 hours. The net weight gain during the experiment, wet-to-dry weight ratio for lung tissue, angiography of the pulmonary artery, pulmonary vascular resistance, color and fluorescence of the lung surface, and alveolar gas diffusion into the perfusate proved to be useful parameters to assess the stability of the preparations and the quality of the experiments. To confirm that an intraparenchymal tumor was perfused via the pulmonary artery, methods to detect avidin and dextran-biotin in tumor tissue after administration into the perfusion solution were employed. Histological examination of bronchial as well as tumor tissue, a computerized histoanalyzation, and a tumor grading program demonstrated that IPHL experiments did not interfere with the grading and staging of the tumors-an important ethical precondition for the use of human preparations in an extracorporeal perfusion model.
体外分离、灌注和通气的人肺（IPHL）模型非常适合多种生理、药理和外科研究，前提是肺内的生理和生化条件能够维持在接近体内的水平。本研究的目的就是开发这样一种模型。所使用的肺标本是因支气管癌切除后获得的。由于在这些解剖标本中肿瘤保持完整，该模型特别适合用于研究抗癌药物的药代动力学和作用。通过进行一系列52次IPHL实验（使用11个全肺标本和41个肺叶标本），我们建立了一个IPHL模型，该模型能够在生理条件下对切除的肺进行2至3小时的体外灌注和通气。实验期间的净重增加、肺组织的湿重与干重比、肺动脉造影、肺血管阻力、肺表面颜色和荧光以及肺泡气体向灌注液中的扩散，被证明是评估标本稳定性和实验质量的有用参数。为了证实实质内肿瘤通过肺动脉灌注，采用了在灌注液中给药后检测肿瘤组织中抗生物素蛋白和葡聚糖 - 生物素的方法。对支气管以及肿瘤组织进行组织学检查、计算机组织分析和肿瘤分级程序表明，IPHL实验不会干扰肿瘤的分级和分期，这是在体外灌注模型中使用人体标本的一个重要伦理前提条件。
