Protective Effect of Nitroglycerin on the Ischemia-Reperfusion Model of the Isolated Rat Lung

Jheon, Sanghoon; Lee, Sub; Lee, Jong Hoon; Son, Bok Kyoung; Cho, Gong Rae; Chung, Jin Yong; Cho, Soung Kyung; Kim, Bong Il; Lee, Young Man; Choh, Joong Haeng

Abstract

BACKGROUND: Protection against ischemia-reperfusion injury is crucial for successful transplantation of the lung. It has been known that nitric oxide has many favorable effects on the donor lungs but at the same time, has some potential side effects of cytotoxicity. In this regards, we investigated whether the administration of nitroglycerin could decrease ischemia-reperfusion injury in isolated rat lung reperfusion model for the confirmation of the effect of nitroglycerin, a donor of nitric oxide, on lung transplantation. MATERIAL AND METHOD: 35 Sprague-Dawley species male white rats were used for this experiment. For nitroglycerin group (n=18), nitroglycerin was administered intravenously followed by mixed in flushing solution for preservation. As a control group (n=17), we used the same amount of normal saline. To evaluate the effect of nitroglycerin on the lung, heart-lung block was obtained, weighed and stored in University of Wisconsin Solution at 10oC for 24 hours. In each group of the isolated lungs, reperfusion was carried out with Krebs-Hensleit-diluted human blood for 60 minutes. As parameters of the state of the isolated lung, peak inspiratory and pulmonary arterial pressures were continuously recorded. Oxygen and carbon dioxide tension of reperfusing blood were measured before and after 30, 60 minutes of reperfusion. After sixty minutes of reperfusion, protein content in bronchoalveolar lavage fluid was measured also for the evaluation of the degree of alveolar flooding. Lung myeloperoxidase activity was determined to verify the accumulation of neutrophils.
RESULTS
Although statistically significant differences were not noted in peak inspiratory and pulmonary arterial pressure between control and nitroglycerin group, latter group showed lowering tendency of pulmonary arterial pressure during the entire reperfusion period. Oxygen tension was higher (p<0.05) in nitroglycerin group compared with that of the control group, in contrast, there were no differences in carbon dioxide tension, protein content in bronchoalveolar lavage fluid and myeloperoxidase activity between the groups. In the examination of ultrastructural changes, nitroglycerin denoted the protective effect on the pulmonary architecture compared with that of control group.
CONCLUSION
Collectively, on the bases of these experimental results, prior treatment of donor lung with nitroglycerin could result in better preservation of the lung. Consequently, these nitroglycerin preserved lungs are thought to be more suitable for successful transplantation of the lung.