Overall, these findings demonstrate kidney and heart protective effects of AZL-M in SHROB, and these effects were associated with its ability to lower blood pressure and improve endothelial function.

Background Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Methods Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. Studies were performed 7 days later. Relative pulmonary and systemic flow to each lung was measured by injection of 99mTc-macroaggregated albumin. Histological sections were examined for structure and necrosis and scored for BOOP. Apoptosis was detected by immunohistochemistry with an antibody against cleaved caspase-3. Results Pulmonary artery blood flow to left lungs was <0.1% of the cardiac output, and bronchial artery circulation was ~2% of aortic artery flow. Histological sections from ischemic left lungs consistently showed Masson bodies, inflammation and young fibroblasts filling the distal airways and alveoli, consistent with BOOP. Quantitative evaluation of BOOP using epithelial changes, inflammation and fibrosis were higher in ischemic left lungs than right or sham-operated left lungs. Apoptosis was increased in areas exhibiting histological BOOP, but there was no histological evidence of necrosis. TLR4 expression was increased in ischemic left lungs over right. Conclusions An occlusive slipknot around the main left PA in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP.