Rat model of left pulmonary artery hypoplasia

Abstract

To create an animal model of pulmonary artery hypoplasia, we banded the left pulmonary artery (LPA) of 9-week Sprague-Dawley rats. Pulmonary artery (PA) architecture was studied by internally casting with Microfil. After anesthetizing and orally intubating, we placed an LPA band via a left lateral thoracotomy and allowed the rats to recover. At various time points (usually 14 days), we injected Microfil into the main PA and sacrificed the animal. Lung tissue was cleared with ethanol and methyl salicylate, preserving the 3D architecture of the lungs. We evaluated the lungs grossly with a stereoscope at 0.63X, then took color Z-stacks of image planes at 4X and converted each image to monochrome. Using Metamorph software, we deconvolved the stack to create a single 2D image, which we then pseudocolored, bringing out the terminal processes of vessels filled with Microfil, allowing for counting and comparison. Post-LPA banding lungs compared grossly with the normal right lungs. The left pulmonary artery architecture was generally less dense and often had dropout peripherally. Terminal branches decreased by 23.1% in the banded vs. the unbanded lung (SE 6.1, N=6). This animal model of unilateral pulmonary artery hypoplasia induced in juvenile rats will allow for the study of angiogenic effects of growth factors, with the intention of translating this knowledge to humans with congenital heart disease.