Endothelium-dependent relaxation of canine pulmonary artery after prolonged lung graft preservation in University of Wisconsin solution: Role of L-arginine supplementation

Background The University of Wisconsin (UW) solution has been demonstrated to enhance pulmonary allograft preservation. Endothelial nitric oxide (NO) production has been shown to be significantly impaired after ischemia and reperfusion (I/R) injury. The present experiments aimed to determine the protective effects of pulmonary endothelium-dependent function by using supplemental NO in University of Wisconsin (UW) solution following prolonged lung graft preservation. Methods Thirty-six healthy mongrel dogs underwent thoracotomy to expose the left lung. In addition to a group given UW solution (n = 4), 100 μmol/liter L-arginine, (n = 7), 100 μmol/liter N ^G-monomethyl-L-arginine (L-NMMA n = 7) and 1.0 μmol/liter 3-morpholinosydnonimine (SIN-1, n = 18 respectively, were added to UW solution, and infused from the aortic root and pulmonary artery to the pulmonary vein. The perfused lung was then allowed to inflate to its maximum volume for 24-hour oxygenated preservation in each supplemented condition of UW solution at 4°C. In the SIN-1 group, the preservation period was further divided into 8 hours and 16 hours, respectively. Rings of the third-order pulmonary artery of the inflated lung were then suspended in organ chambers to measure isometric force. Results Endothelium-dependent relaxation (EDR) to acetylcholine, adenosine diphosphate and sodium fluoride of the pulmonary rings in the L-arginine group was significantly preserved compared with UW-solution-only group. The L-NMMA group showed significant EDR impairment after 24-hour preservation compared with the UW solution group. Similar to the L-arginine group, the SIN-1 group showed significant EDR protection with 8-hour preservation, but not with 24-hour preservation. In contrast, EDR to calcium ionophore A23187 showed no EDR changes after 24-hour preservation in any of the supplemented groups. Conclusions Supplemental L-arginine in UW solution ameliorates impaired pulmonary EDR following prolonged lung preservation of up to 24 hours.