Improved lung preservation using a dimethylthiourea flush.

The purpose of this study was to evaluate the ability of dimethylthiourea (DMTU), a low molecular weight hydroxyl free radical scavenger, to improve preservation of the lung for transplantation. Following preservation, 15 isolated canine left lower lobes were reperfused for 90 min with autologous blood. Five group I lobes served as controls and were not subjected to ischemia prior to reperfusion. Five group II lobes were flushed and submerged in a cold Euro-Collins solution and stored for 4 hr at 4 degrees C prior to reperfusion. Group III lobes were flushed with a 20 mM DMTU-enhanced Euro-Collins solution, stored for 4 hr, and then reperfused. The isogravimetric method was utilized to determine the capillary permeability coefficient (Kfc) for the reperfused lobes. The Kfc values were 0.10 +/- 0.01, 0.17 +/- 0.01, and 0.10 +/- 0.008 ml/min/mm Hg/100 g lung for groups I, II, and III, respectively (P less than 0.01 II vs I, III). Extravascular lung water values in the reperfused lobe were 4.44 +/- 0.45, 6.57 +/- 0.38, and 5.23 +/- 0.22 ml/g blood free dry lung weight for groups I, II, and III (P less than .05, II vs. I, III). Lung lipid peroxidation, measured as thiobarbituric acid-reactive material, was higher in group II, 146 +/- 6 nmole/g, than in either group I, 90 +/- 5 nmole/g, or group III, 91 +/- 4 nmole/g (P less than 0.01). The results indicate that the addition of DMTU improves hypothermic lung preservation by reducing lipid peroxidation and edema formation upon reperfusion.

Reperfusion injury in the lung preserved for 24 hours.

The left lower lobes of 28 canine lungs were isolated, preserved, and then reperfused for 150 minutes. Five groups of lobes were studied: group 1, control (n = 5); group 2, one hour of warm ischemia (n = 5); group 3, one hour of warm ischemia + oxygen free radical scavengers (n = 5); group 4, 24 hours of cold ischemia (n = 8); and group 5, 24 hours of cold ischemia + oxygen free radical scavengers (n = 5). Oxygen free radical scavengers consisted of superoxide dismutase and catalase (100 micrograms/mL) given at the moment of reflow. Extravascular lung water (grams per gram of blood-free dry lobe weight) after reperfusion was 2.75 +/- 0.19, 5.46 +/- 0.60, 4.08 +/- 0.37, 9.43 +/- 0.98, and 6.91 +/- 0.95 for groups 1 through 5, respectively (p less than 0.05, groups 2 through 5 versus group 1; p less than 0.05, group 2 versus group 3 and group 4 versus group 5). Lung tissue lipid peroxidation, measured as thiobarbituric acid reactive material, was 117 +/- 14, 314 +/- 19, and 163 +/- 25 nmol/g dry lobe weight for groups 1, 4, and 5, respectively (p less than 0.05, group 4 versus group 1 and group 4 versus group 5). The data suggest that oxygen free radical scavengers attenuate reperfusion injury after long-term hypothermic lung preservation.