Submitted on October 9, 2006
Accepted on April 18, 2007
Effects of Pulmonary Ischemia on Lung Morphology
Michael J Fields1, John M Bishai1, Wayne Mitzner1, and Elizabeth M. Wagner1*
1 Pediatrics, Medicine and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland, United States
* To whom correspondence should be addressed. E-mail: wagnerem{at}jhmi.edu.
Pulmonary ischemia resulting from chronic pulmonary embolism leads to proliferation of the systemic circulation within and surrounding the lung. However, it is not clear how well alveolar tissue is sustained during the time of complete pulmonary ischemia. In the present study, we investigated how pulmonary ischemia after left pulmonary artery ligation (LPAL) would alter lung mechanical properties and morphology. In this established mouse model of lung angiogenesis after chronic LPAL (10), we evaluated lung function and structure before (3 days) and after (14 days) a functional systemic circulation to the left lung is established. Age matched naive and sham operated C57Bl/6 mice, and mice undergoing chronic LPAL were studied. Left and right lung pressure-volume relationships were determined. Next, lungs were inflated in situ with warmed agarose (25-30 cmH2O), fixed, and mean chord lengths (MCL) of histological sections were quantified. MCL of naive mice averaged 43.9±1.8 µm. No significant changes in MCL were observed at either time point after LPAL. Left lung volumes and specific compliances were significantly reduced 3 days after LPAL. However, by 14 days after LPAL, lung pressure-volume relationships were not different from controls. These results suggest that severe pulmonary ischemia causes changes in lung mechanics early after LPAL that are reversed by the time a new systemic vasculature is known to perfuse pulmonary capillaries. The LPAL model thus affords a unique opportunity to study lung functional responses to tissue ischemia and subsequent recovery.
