Pierre A F, Xavier A M, Liu M, Cassivi S D, Lindsay T F, Marsh H C, Slutsky A S, Keshavjee S H
Division of Thoracic Surgery, The Toronto Hospital, Ontario, Canada.
Transplantation. 1998 Sep 27;66(6):723-32. doi: 10.1097/00007890-199809270-00006.
Lung dysfunction after transplantation continues to be a significant clinical problem. Soluble complement receptor 1 (sCR1) is a potent inhibitor of complement activation. We evaluated the inhibitory effect of sCR1 on complement activation and reperfusion injury in pig lung allografts.
In a randomized and blinded study, left lung transplantation was performed in 13 pigs. Donor lungs were flushed and then stored for 30 hr at 4 degrees C. Control pigs (n=7) received saline, and the treatment group (n=6) received 15 mg/kg sCR1 1 hr before reperfusion. One hour after reperfusion, the right pulmonary artery was clamped for 10 min to assess the function of the transplanted lung. Pulmonary function was assessed again on day 3.
Complement inhibition was 93% in the sCR1 group and returned to baseline (8% inhibition) after 3 days. There was a trend toward a higher partial pressure of oxygen at 1 hr in the sCR1 group compared with the control group (mean +/- SE: 408+/-42 mmHg vs. 288+/-69 mmHg, P = 0.19). Alveolar ventilation was better in the sCR1 group than in the control group (P = 0.01) at 1 hr. Mixed venous saturation was significantly lower in the control group at both 1 hr (P = 0.02) and 3 days (P = 0.001). The wet/dry weight of the lung tissue was lower in the sCR1 group compared with the control group on day 3 (P < 0.05). Chemiluminescence, an index of phagocyte priming, was lower in the sCR1 group when cells were stimulated with complement opsonized zymosan but not when stimulated with zymosan or phorbol myristate acetate.
sCR1 improves ventilation, reduces pulmonary edema, and may be beneficial in improving posttransplant lung oxygenation.
移植后肺功能障碍仍然是一个重大的临床问题。可溶性补体受体1（sCR1）是补体激活的有效抑制剂。我们评估了sCR1对猪肺同种异体移植中补体激活和再灌注损伤的抑制作用。
在一项随机双盲研究中，对13头猪进行左肺移植。供体肺冲洗后，在4℃下保存30小时。对照组（n = 7）接受生理盐水，治疗组（n = 6）在再灌注前1小时接受15mg/kg sCR1。再灌注1小时后，夹闭右肺动脉10分钟以评估移植肺的功能。在第3天再次评估肺功能。
sCR1组补体抑制率为93%，3天后恢复至基线水平（抑制率8%）。与对照组相比，sCR1组在1小时时氧分压有升高趋势（均值±标准误：408±42mmHg对288±69mmHg，P = 0.19）。在1小时时，sCR1组的肺泡通气优于对照组（P = 0.01）。对照组在1小时（P = 0.02）和3天（P = 0.001）时混合静脉血氧饱和度均显著降低。在第3天，sCR1组肺组织的湿/干重低于对照组（P < 0.05）。当用补体调理酵母聚糖刺激细胞时，sCR1组的化学发光（吞噬细胞激活指数）较低，但用酵母聚糖或佛波酯肉豆蔻酸酯刺激时则不然。
sCR1可改善通气，减轻肺水肿，可能有助于改善移植后肺的氧合。
