Johnston M R, Christensen C W, Minchin R F, Rickaby D A, Linehan J H, Schuller H M, Boyd M R, Dawson C A
Surgery. 1985 Jul;98(1):35-44.
The objectives of this study were to develop a surgical procedure that would allow for bilateral isolated lung perfusion in vivo as a means of delivering organ-specific chemotherapy and to evaluate the influence of the procedure on certain pulmonary physiologic parameters. The sterile surgical procedure that was carried out in dogs involved the setting up of two separate perfusion circuits. Once standard systemic cardiopulmonary bypass was established, a second circuit was devised to perfuse the lungs by placing an inflow cannula into the main pulmonary artery and collecting venous effluent in the left atrium. Cross-contamination between perfusion circuits was determined in acute studies with labeled plasma protein or red blood cells and was found to be in an acceptable range if the aorta was cross-clamped and the heart arrested. Only about 0.4 ml/min of pulmonary perfusate leaked into the systemic circulation, indicating that systemic toxicity should not be a major concern when chemotherapy agents are added to the pulmonary perfusate. Chronic studies demonstrated that hemodynamic parameters, lung water, pulmonary endothelial serotonin extraction, and histologic findings all showed minimal changes after 50 minutes of isolated lung perfusion. Five days after perfusion, lung dynamic compliance and peak serotonin extraction showed significant decreases. However, all of the measured parameters had returned toward baseline levels by the end of the 8-week postoperative study period. The procedure offers significant advantages over the previously described single lung perfusion and may provide a method of delivering immediate high-concentration adjuvant chemotherapy to coincide with resection of primary or metastatic lung tumors.
本研究的目的是开发一种手术方法，该方法能够在体内实现双侧孤立肺灌注，以此作为输送器官特异性化疗药物的一种手段，并评估该手术方法对某些肺生理参数的影响。在犬类身上实施的无菌手术过程包括建立两个独立的灌注回路。一旦建立标准的全身心肺转流，通过将流入插管置入主肺动脉并在左心房收集静脉流出液来设计第二个回路以灌注肺脏。在使用标记血浆蛋白或红细胞的急性研究中确定了灌注回路之间的交叉污染情况，并且发现如果夹闭主动脉并使心脏停搏，交叉污染在可接受范围内。仅有约0.4毫升/分钟的肺灌注液漏入体循环，这表明当向肺灌注液中添加化疗药物时，全身毒性不应成为主要担忧。慢性研究表明，在进行50分钟的孤立肺灌注后，血流动力学参数、肺水含量、肺内皮5-羟色胺摄取以及组织学结果均显示出最小程度的变化。灌注后5天，肺动态顺应性和5-羟色胺摄取峰值出现显著下降。然而，在术后8周的研究期结束时，所有测量参数均已恢复至基线水平。该手术方法相较于先前描述的单肺灌注具有显著优势，并且可能提供一种在切除原发性或转移性肺肿瘤时同时给予即时高浓度辅助化疗的方法。
