|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1996 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1995 : ¥1,300,000 (Direct Cost : ¥1,300,000)
The standard clinical protocol for lung transplantation employs cold single pulmonary artery flush with Euro-Collins solution (ECS) or the University of Wisconsin solution (UWS). Prostaglandin El (PGE1) is usually given by direct injection into the pulmonary artery to reduce pulmonary vasoconstriction caused by high-potassium condition, however, the efficacy of PGE1 on lung preservation remains controversial. In the first experimental study using an isolated perfused rat lung model, we demonstrated that vasodilatory effects of PGE1 were markedly reduced under a high-potassium condition, and that potassium-induced pulmonary vasoconstriction were inhibited by calcium channel blocker nifedipine (Shigeyuki Sasaki, Keishu Yasuda, et al. Does PGE1 attenuate potassium-induced vasoconstriction in initial pulmonary artery flush on lung preservation? Submitted to The Journal of Heart and Lung Transplantation). Based on these results, we carried out the transplantation study using a rat lung tran
splant model which we have previously developed. The excised rat lungs (n=30) were flushed with either UWS with a prior injection of 50 mug/kg PGE1 into the pulmonary artery (UWS+PGE1 ; n=7) , UWS only (UWS ; n=7) , or UWS containing nifedipine (UWS+Nif ; n=8). After cold storage for 24 hours, all lungs were reperfused for 2 hours using an isolated, pulsatile blood perfused lung model. Control lungs (n=8) were reperfused immediately after harvest. Blood gas analysis and shunt fraction, lung airway resistance, dynamic lung compliance, and pulmonary vascular resistance were assessed. The pO2 in UWS and UWS+PGE1 group during the perfusion period were significantly deteriorated than those in UWS+Nif group. Shunt fraction, lung airway resistance, and dynamic lung complaince also demonstrated the superiority of UWS+Nif group. In conclusion, the early graft function after storage was significantly enhanced in lungs flushed with UWS containing nifedipine. Calcium channel blocker is more effective than PGE1 in reducing the potassium-induced vasoconstriction. Pretreatment with PGE1 prior to lung harvest in the current program should be replaced with the use of calcium hannel blocker (Shigeyuki Sasaki, Keishu Yasuda, et al.Calcium Channel Blocker Enhances Lung Preservation. Submitted to The Journal of Heart and Lung Transplantation).
次に肺保存モデルを確立する必要があったため、UW液を用いたラット肺保存(0,4,18,24時間保存)を行って肺保存標準モデルを確立し、その結果を英文論文(ShigeyukiSasaki,Keishu Yasuda,et al.A reliable eighteen‐hour rat lung preservation model with a pulsat‐ile perfusion system.)として英文誌The Japanese Journ‐al of Thoracic and Cardiovascular Surgeryに投稿した。この肺保存モデルを用いた研究では、Nifedipine(10-6M)を加えたUW液で初回灌流を行ったラット肺は、保存後の酸素化能、肺コンプライアンスなど対照肺(保存なし)と同様の優れた肺機能を示し、予想通りの結果が得られた。この結果は英文論文(Shigeyuki Sasaki,Keishu Yasuda,et al.Calcium Channel Blocker En‐hances Lung Preservation.)として英文誌The Journal ofHeart and Lung Transplantationに投稿した。投稿英文論文(3編)の内容は「科学研究費補助金研究成果報告書」に記載する予定である。 Less