Development of a unilateral porcine emphysema model induced by porcine pancreatic elastase.

Abstract

Emphysema is one of the pathological hallmarks of chronic obstructive pulmonary disease. We have recently reported that radiofrequency therapy improves lung function in rodent models of emphysema. However, preclinical data using large animals is necessary for clinical translation. Here, we describe the work performed to establish a unilateral porcine emphysema model. Different doses of porcine pancreatic elastase (PPE) were instilled into the left lung of ten Yucatan pigs. Three additional pigs were used as controls. Six weeks after instillation, lungs were harvested. Lung compliance was measured by a water displacement method and plethysmography. Systematic uniform random sampling of left and right lungs was performed independently to measure alveolar surface area using micro-computed tomography (CT) and histology. In pigs instilled with 725-750 U/Kg of PPE (PPE group, n=6), the compliance of the left lung was significantly higher by 37.6% than that of the right lung (p=0.03) using the water displacement method. With plethysmography, the volume of the left lung was significantly larger than that of the right lung at 3, 5, and 10 cmH2O. Measurements from either micro-CT or histology images showed a significant decrease of alveolar surface area by 14.2 % or 14.5 % (p=0.031) in the left lung compared to the right lung of the PPE group. A unilateral model for mild emphysema in Yucatan pigs has been established, which can now be used for evaluating novel therapeutics and interventional strategies.