Early graft dysfunction after lung transplantation is a significant and unpredictable problem. Our study aimed at a detailed investigation of structure-function correlations in a rat isolated heart-lung model of ischemia/ reperfusion injury.
Variable degrees of injury were induced by preservation with potassiummodified Euro-Collins solutions, 2 hr of cold ischemia, and 40 min of reperfusion. Pulmonary artery pressure (P pa ), pulmonary vascular resistance (PVR), peak inspiratory pressure (PIP), and perfusate gases (โฌP O2 , โฌP CO2 ) were recorded during reperfusion. Right lungs were used to calculate W/D-weight ratios. Nineteen experimental and six control left lungs were fixed for light and electron microscopy by vascular perfusion. Systematic random samples were analyzed by stereology to determine absolute and relative volumes of lung structures, the amount of interstitial and intraalveolar edema, and the extent of epithelial injury. Lectin-and immunohistochemistry using established epithelial cell markers were performed in three animals per group to reveal sites of severe focal damage.
Experimental lungs showed a wide range in severity of ischemia/ reperfusion injury. Intraalveolar edema fluid amounted to 77-909 mm 3 with a mean of 448ฯฎ250 mm 3 as compared with 22ฯฎ22 mm 3 in control lungs (Pฯฝ0.001). Perfusate oxygenation (โฌP O2 ) decreased from 30.5ฯฎ15.2 to 21.7ฯฎ15.2 mm Hg (Pฯญ0.05) recorded after 5 and 40 minutes of reperfusion. In experimental lungs, a surface fraction of 1% to 58% of total type I pneumocyte surface was damaged. Intraalveolar edema per gas exchange region (Vv ape,P) and โฌP O2 were related according to โฌP O2 ฯญ 96 ฯช 60 ฯซ log 10 (Vv ape,P) [mm Hg]. The extent of epithelial injury did not correlate with โฌP O2 nor with intraalveolar edema, but increased significantly with PVR. Lectin-and immunohistochemistry revealed focal severe damage to the alveolar epithelium at the border of perivascular cuffs.