THE EX-VIVO ISOLATED, PERFUSED HUMAN LUNG MODEL - DESCRIPTION AND POTENTIAL APPLICATIONS

An ex-vivo isolated, perfused, and ventilated human lung (IPHL) model is well suited for many kinds of physiological, pharmacological, and s urgical 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 availabl e after resection because of bronchial carcinoma. Since the tumor rema ins intact in these anatomical preparations, this model is particularl y suitable for investigation of the pharmacokinetics and effects of an ti-cancer agents. Carrying out a series of 52 IPHL experiments (with 1 1 whole-lung preparations and 41 lobe preparations), we have establish ed 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 lun g tissue, angiography of the pulmonary artery, pulmonary vascular resi stance. color and fluorescence of the lung surface, and alveolar gas d iffusion into the perfusate proved to be useful parameters to assess t he stability of the preparations and the quality of the experiments, T o confirm that an intraparenchymal tumor was perfused via the pulmonar y artery, methods to detect avidin and dextran-biotin in tumor tissue after administration into the perfusion solution were employed. Histol ogical examination of bronchial as well as turner tissue, a computeriz ed histoanalyzation, and a tumor grading program demonstrated that IPH L experiments did not interfere with the grading and staging of the tu mors - an important ethical precondition for the use of human preparat ions in an extracorporeal perfusion model.