Chiang, Chi-Huei, Kang Hsu, Horng-Chin Yan, Horng-Jyh Harn, and Deh-Ming Chang. PGE₁, dexamethasone, U-74389G, or Bt₂-cAMP as an additive to promote protection by UW solution in I/R injury. J. Appl. Physiol. 83(2): 583-590, 1997.A method to reduce ischemia-reperfusion (I/R) injury can be an important criterion to improve the preservation solution. Although University of Wisconsin solution (UW) works as a lung preservation solution, its attenuation effect on I/R injury has not been investigated. We attempted to determine whether, by adding various protective agents, modified UW solutions will enhance the I/R attenuation by UW. We examined the I/R injury in an isolated rat lung model. Various solutions, e.g., physiological salt solution (PSS), UW, and modified UW solutions containing various protective agents such as prostaglandin E₁, dexamethasone, U-74389G, or dibutyryl adenosine 3,5-cyclic monophosphate were perfused individually to evaluate the I/R injury. Isolated rat lung experiments, with ischemia for 45 min, then reperfusion for 60 min, were conducted in a closed circulating system. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficient (K_fc), protein content of lavage fluid, concentration of cytokines, and lung histopathology were analyzed. Results showed that the acute I/R lung injury with immediate permeability pulmonary edema was associated with an increase in tumor necrosis factor- (TNF-) production. A significant correlation existed between TNF- and K_fc (r = 0.8, P < 0.0001) and TNF- and LWG (r = 0.9, P < 0.0001), indicating that TNF- is an important cytokine modulating early I/R injury. Significantly lower levels of K_fc, LWG, TNF-, and protein concentration of lung lavage (P < 0.05) were found in the UW-perfused group than in the control group perfused with PSS. Modified UW promoted the protective effect of UW to further decrease K_fc, LWG, and TNF- (P < 0.05). Histopathological observations also substantiated this evidence. In the UW+U-74389G group, bronchial alveolar lavage fluid contained lowest protein concentration. We conclude that the UW solution attenuates I/R injury of rat lung and that the modified UW solutions further enhance the effect of UW in reducing I/R injury. Among modified solutions, UW+U-74389G is the best. Further investigation of the improved effects of the modified UW solutions would be beneficial in lung transplantation.