IPL- Isolated-perfused lung

© Fraunhofer ITEM, Ralf Mohr
The ex-vivo model “Isolated Perfused Rat Lung” (IPL) allows simulation of whole-organ exposure to inhalable substances. Due to this proximity to the in-vivo situation, the isolated perfused rat lung is an attractive tool for preclinical testing of new drug candidates and formulations as well as for acute toxicity testing of chemicals.

At Fraunhofer ITEM, the IPL has recently been established as a tool for investigations into the systemic uptake of inhaled substances through the lung. To this end, lungs from rats are ventilated and perfused with a physiologic buffer solution. Respiratory parameters, such as tidal volume, dynamic compliance, and pulmonary arterial pressure (VT, Cdyn, PAP), are measured online for monitoring of pulmonary viability.

For investigations into mass transfer processes through the lung, IPLs are exposed to rat-respirable aerosols. The concentration profile of the substance is subsequently analyzed in the perfusate.

Studies at Fraunhofer ITEM have shown that the analysis of such concentration profiles for small molecules delivered to the lungs as aerosols enables a qualitative ranking in regard to the transfer velocity through the lung into the systemic circulation, which is in good agreement with data from human clinical trials.

These experiments as well as further studies performed at Fraunhofer ITEM show a strong potential of the model for systematic investigations of mass transfer through the lung for different substances, though a quantitative comparison to the human situation and in this context between different products has not been carried out yet. In the context of absorption studies, the IPL model is also useful for further mechanistic investigations, such as the elucidation of transport-relevant mechanisms through the alveolar-epithelial membrane. 

Analysis options

 

Test substances can be from any source (medications, chemicals,  environmental pollutants etc.) and aerosol generation can be performed for both solid and liquid materials.

Besides the relevant inhaled substances, biomarkers can be analyzed in bronchoalveolar lavage fluid and lung perfusate. 

Imaging

  • Conventional staining, tissue pathohistology and conventional microscopy
  • Immunohistochemistry and fluorescence microscopy 
  • Confocal and electron microscopy

Chemical analysis

  • HPLC
  • LC/GC-MS

Lung function

  • Ex-vivo measurement of dynamic compliance (Cdyn), lung resistance (RL), and pO2 in perfusate 
  • Analysis of lung weight (edema, atelectasis formation) 
  • Perfusion flow, pulmonary artery/venous pressure

Other technologies

 

Predictive platform technologies for safety and efficacy testing: