A murine model of lung ischemia and reperfusion injury: tricks of the trade.

Abstract

BACKGROUND: Pulmonary ischemia-reperfusion injury (IRI) causes postoperative morbidity in patients undergoing lung transplantation, isolated lung perfusion, and cardiopulmonary bypass and may lead to potentially lethal pathologies such as respiratory shock. In-depth study of this pathology requires a reliable animal model. Mice are a popular species to develop experimental models because of their logistic advantages and the availability of knock outs. However, their small size warrants microsurgical techniques and a skilled surgeon. MATERIALS AND METHODS: We developed a murine model of pulmonary anoxic IRI through hilar clamping using adult female Swiss mice. After left thoracotomy, we expose the pulmonary hilum keeping the ribs and the muscles of back and forepaw intact. A microvascular clamp is placed over the entire hilum, occluding bronchus, pulmonary artery, and vein. RESULTS: Our model proved to be simple, reliable, and reproducible, showing minimal preoperative and postoperative mortality. Histopathologic analysis indicated all characteristic features of pulmonary IRI, such as an early recruitment of lymphocytes followed by neutrophil influx. CONCLUSIONS: This article presents a murine surgery model for pulmonary IRI based on a muscle-sparing thoracotomy. The minimal approach limits manipulation of lung tissue, minimizing mortality and non-IRI-induced injury.