The Effects of addition of Cyclic Adenosine Monophosphate and NItric Oxide in Low Potassium Dextran Solution for Lung Preservation in an Isolated Rabbit Lung Perfusion Model

Cho, Deog Gon; Cho, Kyu Do; Kim, Young Du; Kwack, Moon Sub

Abstract

BACKGROUND: During organ preservation and reperfusion, both cyclic adenosine monophos-phate(cAMP) and nitric oxide(NO) play a central role in maintaining pulmonary vascular homeostasis. However , both cAMP and NO levels decline markedly during pulmonary ischemia and reperfusion. In this study we prepared a new solution in which a cAMP analog(dibutyryl cAMP, db-cAMP) and a nitric oxide donor (nitroglycerin, NTG) were added to the conventional low potassium dextran(LPD) solution. We investigated the effects of addition of cAMP and/or NO in LPD solution for lung preservation and compared the effectiveness of the solutions. MATERIAL AND METHOD: Rabbit lung grafts(six per group) were studied in an isolated lung perfusion model. The heart-lung blocks were harvested after flushing in situ with only LPD solution(group I, n = 6), plus NTG(group II, n = 6), plus db-cAMP(group III, n = 6), or plus NTG and db-cAMP(group IV, n = 6), and were preserved at 10degreesC for 24 hours. The stored lungs were ventilated with 100% oxygen and reperfused with fresh venous blood at 38degreesC for 30 minutes. We assessed the lung functions and subsequent lung edema. Tumor necrosis factor alpha(TNF-alpha) and nitrite/nitrate(total NO production) levels were also measured. In addition, we evaluated histologic and ultrastructual changes of the reperfused lungs. RESULT: Although Group IV demonstrated the best lung preservation, the differences were not significant among group II, III and IV. Group Irevealed the worst lung functions and severe pulmonary edema(p<0.05 versus all other groups). Although group II showed better lung preservation than in group III, the differences were not significant. TNF-alpha release was significantly reduced in group IV than in group I after reperfusion(p<0.01). NO levels were significantly increased in groups II and IV than in groups I and III after reperfusion(p<0.001). However , there were no significant differences between groups I and III or between groups II and IV. NO levels decreased gradually in groups I and III(p<0.05). Histologic and ultrastructual studies showed better preservation of the alveolar-capillary barrier in groups II, III and IV than in group I.
CONCLUSION
This study demonstrate that both of db-cAMP and NTG had beneficial effects on lung preservation with LPD solution, and there was no difference in the effect of each component. Especially, we expect that combined supplementation of db-cAMP and NTG will preserve better vascular homeostasis and minimize reperfusion inj ury after ischemic cold storage.