Tremblay Alain, Kearney Christine T, Hanks Chris, Hughes Hanks Jennifer, White David S, Pereira Marcia E, Zook Craig E, Sargis Karen, Zhang Luke
a Department of Medicine , University of Calgary Cumming School of Medicine , Calgary , AB. Canada.
b Becton, Dickinson and Company Inc. , Vernon Hills , Illinois , USA.
Exp Lung Res. 2017 Nov-Dec;43(9-10):388-394. doi: 10.1080/01902148.2017.1384865. Epub 2017 Dec 4.
Purpose/Aim of the study: This study assessed the safety and potential toxicity of a silver nitrate coated indwelling pleural catheter (SNCIPC) designed to create pleurodesis in a large animal model.
Sixteen animals underwent insertion of either a SNCIPC or an uncoated silicone catheter. Half of the animals were sacrificed at day 7 and the others at day 30. Animal weight and assessment of well-being, pleural fluid and blood collection were performed at regular intervals. Pleurodesis was assessed at necropsy and histopathological examination of organs performed.
No mortality or significant clinical findings were observed throughout the experiment. SNCIPC treated animals had increased pleural fluid drainage overall (p < 0.001) and specifically on days 1-4. No differences in hemoglobin, white blood cell count or neutrophil counts were detected between groups. No treatment related histological findings were observed in any of the evaluated tissues outside of the treated area. Serum silver levels in SNCIPC catheter treated animals peaked on Day 4 (0.185 μg/mL, 30 day group) then gradually decreased for the remainder of the study period. The highest tissue silver concentrations were noted in the SNCIPC groups in tissues close to the treatment site in addition to the liver (59.8ug/g +/- 8.6 and 73.3ug/g +/- 25). Pleurodesis scores were significantly higher in SNCIPC treated animals for both the 7 day (median 6.5 vs. 1.0, p = 0.029) and 30 day cohorts (median 7.0 vs. 1.5, p = 0.029).
SNCIPC are well tolerated and not associated with any significant signs of toxicity. Silver levels were elevated in local tissues, serum and liver but without evidence of pathological impact. Effective pleurodesis was present by day 7 and more established by day 30. Clinical studies to investigate the safety and efficacy of this device in patients with malignant pleural effusions appear warranted.
研究目的：本研究评估了一种设计用于在大型动物模型中形成胸膜固定术的硝酸银涂层留置胸膜导管（SNCIPC）的安全性和潜在毒性。
16只动物接受了SNCIPC或未涂层硅胶导管的插入。一半动物在第7天处死，另一半在第30天处死。定期测量动物体重并评估其健康状况、采集胸水和血液。在尸检时评估胸膜固定术，并对器官进行组织病理学检查。
在整个实验过程中未观察到死亡或明显的临床发现。接受SNCIPC治疗的动物总体胸水引流量增加（p < 0.001），特别是在第1 - 4天。两组之间在血红蛋白、白细胞计数或中性粒细胞计数方面未检测到差异。在治疗区域以外的任何评估组织中均未观察到与治疗相关的组织学发现。接受SNCIPC导管治疗的动物血清银水平在第4天达到峰值（0.185μg/mL，30天组），然后在研究期的剩余时间逐渐下降。除肝脏外，SNCIPC组中靠近治疗部位的组织中银浓度最高（59.8μg/g ± 8.6和73.3μg/g ± 25）。在第7天（中位数6.5对1.0，p = 0.029）和第30天队列（中位数7.0对1.5，p = 0.029）中，接受SNCIPC治疗的动物胸膜固定术评分均显著更高。
SNCIPC耐受性良好，且与任何明显的毒性迹象无关。局部组织、血清和肝脏中的银水平升高，但无病理影响的证据。到第7天出现了有效的胸膜固定术，到第30天更加稳固。对该装置在恶性胸腔积液患者中的安全性和有效性进行临床研究似乎是必要的。
