Du Z Y, Hicks M, Winlaw D, Spratt P, Macdonald P
Cardiopulmonary Transplant Unit, St. Vincent's Hospital, Darlinghurst, NSW, Australia.
J Heart Lung Transplant. 1996 Dec;15(12):1258-67.
Ischemic preconditioning achieved by brief periods of ischemia and reperfusion before a prolonged period of ischemia can significantly reduce the extent of cardiac damage in many mammalian species and human beings. In this study we used a rat model of single lung transplantation to show that ischemic preconditioning also occurs in the lung.
Rats randomly selected for ischemic preconditioning had their left main bronchus and pulmonary artery occluded for 5 minutes, followed by 10 minutes of reperfusion and ventilation. Lungs of control rats were ventilated for 15 minutes. The lungs were perfused with University of Wisconsin solution, then heart and lungs were excised en bloc and stored in University of Wisconsin solution at 0 degree C for 6 or 12 hours. After left pneumonectomy, the left lung of the donor was then implanted into the recipient via left thoracotomy. After 1 hour of ventilation and reperfusion, a right pneumonectomy was performed making the animal completely dependent on the transplanted lung. Samples of arterial blood from the left ventricle were then taken for arterial oxygen tension and arterial carbon dioxide tension determination. Water contents of the donor lungs were measured before and after reperfusion. Thiobarbituric acid reactive substances were measured in the right donor lung after storage.
Lungs transplanted after 12 hours of storage had profoundly impaired gas exchange (arterial oxygen tension = 34 +/- 5; arterial carbon dioxide tension = 69 +/- 7 mm Hg) compared with the normal levels in the 6-hour storage group (arterial oxygen tension = 308 +/- 22; arterial carbon dioxide tension = 17 +/- 1 mm Hg). Ischemic preconditioning significantly improved gas exchange in the 12-hour storage group (arterial oxygen tension = 83 +/- 11; arterial carbon dioxide tension = 40 +/- 4 mm Hg). Ischemic preconditioning also significantly decreased thiobarbituric acid reactive substances formation at both 6- and 12-hour storage.
These results show that the phenomenon of ischemic preconditioning occurs in the lung and that it may reduce injury to the donor lung during prolonged cold ischemic storage.
在长时间缺血之前,通过短暂的缺血和再灌注实现的缺血预处理可显著降低许多哺乳动物和人类的心脏损伤程度。在本研究中,我们使用单肺移植大鼠模型来表明肺中也会发生缺血预处理。
随机选择用于缺血预处理的大鼠,其左主支气管和肺动脉被阻断5分钟,随后进行10分钟的再灌注和通气。对照大鼠的肺通气15分钟。用威斯康星大学溶液灌注肺,然后将心脏和肺整块切除,并在0℃下保存在威斯康星大学溶液中6或12小时。左肺切除术后,将供体的左肺通过左胸切开术植入受体。通气和再灌注1小时后,进行右肺切除术,使动物完全依赖移植肺。然后从左心室采集动脉血样本,用于测定动脉血氧分压和动脉血二氧化碳分压。在再灌注前后测量供体肺的含水量。在储存后测量右供体肺中的硫代巴比妥酸反应性物质。
与6小时储存组的正常水平(动脉血氧分压 = 308 ± 22;动脉血二氧化碳分压 = 17 ± 1 mmHg)相比,储存12小时后移植的肺气体交换严重受损(动脉血氧分压 = 34 ± 5;动脉血二氧化碳分压 = 69 ± 7 mmHg)。缺血预处理显著改善了12小时储存组的气体交换(动脉血氧分压 = 83 ± 11;动脉血二氧化碳分压 = 40 ± 4 mmHg)。缺血预处理在6小时和12小时储存时也显著减少了硫代巴比妥酸反应性物质的形成。
这些结果表明缺血预处理现象发生在肺中,并且它可能减少长时间冷缺血储存期间对供体肺的损伤。