Bronchoscopic lung volume reduction using tissue engineering principles

Bronchoscopic lung volume reduction using tissue engineering principles
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DOI:
10.1164/rccm.200208-842oc
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发表时间:
2003-03-01
影响因子:
24.7
通讯作者:
Hoffman, A
Hoffman, A
中科院分区:
医学1区
文献类型:
--
作者:
Ingenito, EP;Berger, RL;Hoffman, A

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采用基于组织工程学原理的微创肺减容术(BLVR),对6只患木瓜蛋白酶诱导的实验性肺气肿(EMPH)的绵羊进行了肺减容术。在基础状态、EMPH发生后、BLVR后3周和9周进行生理学测量,包括肺容量、弥散量(DLCO)、肺和胸壁的压力-体积关系、呼吸肌肉主动收缩时产生的胸膜压力、肺阻力和动态弹性。动物模型表现出过度充气(总肺活量变化+8%;残气量变化+66%),DLCO减少(-21%),呼吸道阻力增加(+76%),类似于晚期人类EMPH。BLVR耐受性良好,没有并发症,它减少了肺容量(总肺活量变化-16%;残气量变化-55%),导致肺活量显著改善(10%)。在尸检中,在36个治疗部位中有33个(91%)观察到与组织收缩相关的组织良好的周边疤痕。没有感染、脓肿、肉芽肿形成或过敏反应的证据。由BLVR产生的疤痕组织取代了过度膨胀的肺,减少了总肺容量,并安全和持续地改善了呼吸功能。这项研究中使用的BLVR技术解决了我们之前尝试BLVR治疗时发现的局限性,似乎足够安全和有效,足以证明在人体上进行试验是合理的。
Bronchoscopic lung volume reduction (BLVR), a minimally invasive procedure based on tissue engineering principles, was performed in six sheep with papain-induced experimental emphysema (EMPH). Physiologic measurements, at baseline, after generation of EMPH, and at 3 and 9 weeks after BLVR, included lung volumes, diffusing capacity (DLCO), pressure-volume relationships for the lung and chest wall, pleural pressures generated during active respiratory muscle contraction, lung resistance and dynamic elastance. The animal model displayed hyperinflation (change in total lung capacity +8%; change in residual volume +66%), reduced DLCO (-21%), and elevated airway resistance (+76%) that resembled advanced human EMPH. BLVR was well tolerated without complications, and it reduced lung volumes (change in total lung capacity -16%; change in residual volume -55%) in a pattern that resulted in significant improvements in vital capacity (10%). At autopsy, well-organized, peripheral scars associated with tissue contraction were observed at 33 of the 36 (91%) treated sites. There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyperinflated lung, reduced overall lung volume, and improved respiratory function safely and consistently. The BLVR technology employed in this study addresses the limitations identified in our prior attempt at BLVR therapy and appears safe and effective enough to justify a trial in humans.