Background

Artificial lungs have the potential to serve as a bridge to transplantation or recovery for children with end-stage lung disease dependent on extracorporeal life support, but such devices currently require systemic anticoagulation. We describe our experience using the novel Nitric Oxide (NO) Surface Anticoagulation (NOSA) system—an NO-releasing circuit with NO in the sweep gas—with the Pediatric MLung—a low-resistance, pumpless artificial lung.

Methods

NO flux testing: MLungs (n = 4) were tested using veno-venous extracorporeal life support in a sheep under anesthesia with blood flow set to 0.5 and 1 L/min and sweep gas blended with 100 ppm NO at 1, 2, and 4 L/min. NO and NO₂ were measured in the sweep and exhaust gas to calculate NO flux across the MLung membrane. Pumpless implants: Sheep (20–100 kg, n = 3) underwent thoracotomy and cannulation via the pulmonary artery (device inflow) and left atrium (device outflow) using cannulae and circuit components coated with an NO donor (diazeniumdiolated dibutylhexanediamine; DBHD-N₂O₂) and argatroban. Animals were connected to the MLung with 100 ppm NO in the sweep gas under anesthesia for 24 h with no systemic anticoagulation after cannulation.

Results

NO flux testing: NO flux averaged 3.4 ± 1.0 flux units (x10⁻¹⁰ mol/cm²/min) (human vascular endothelium: 0.5–4 flux units). Pumpless implants: 3 sheep survived 24 h with patent circuits. MLung blood flow was 716 ± 227 mL/min. Outlet oxygen saturation was 98.3 ± 2.6%. Activated clotting time was 151±24 s. Platelet count declined from 334,333 ± 112,225 to 123,667 ± 7,637 over 24 h. Plasma free hemoglobin and leukocyte and platelet activation did not significantly change.

Conclusions

The NOSA system provides NO flux across a gas-exchange membrane of a pumpless artificial lung at a similar rate as native vascular endothelium and achieves effective local anticoagulation of an artificial lung circuit for 24 h.

中文翻译：

---

无需全身抗凝的无泵人工肺：一氧化氮表面抗凝系统

背景

人工肺有可能成为依赖体外生命支持的终末期肺病儿童移植或康复的桥梁，但此类装置目前需要全身抗凝。我们描述了我们使用新型一氧化氮 (NO) 表面抗凝 (NOSA) 系统（扫气中含有 NO 的 NO 释放回路）和小儿 MLung（一种低阻力、无泵人工肺）的经验。

方法

NO 通量测试：MLungs（n  = 4）在麻醉下使用静脉-静脉体外生命支持进行测试，血流量设置为 0.5 和 1 L/min，吹扫气体与 100 ppm NO 混合，浓度为 1、2 和 4升/分钟。测量吹扫气和废气中的NO 和 NO _{2以计算穿过 MLung 膜的 NO 通量。}Pumpless implants: Sheep (20–100 kg, n  = 3) underwent thoracotomy and cannulation via the pulmonary artery (device inflow) and left atrium (device outflow) using cannulae and circuit components coated with an NO donor (diazeniumdiolated dibutylhexanediamine; DBHD-N ₂氧₂) 和阿加曲班。动物在麻醉下连接到 MLung，在吹扫气体中含有 100 ppm NO，插管后不进行全身抗凝治疗 24 小时。

结果

NO 通量测试：NO 通量平均为 3.4 ± 1.0 通量单位 (x10 ^-10  mol/cm ² /min)（人血管内皮：0.5–4 通量单位）。无泵植入物：3 只绵羊在专利电路下存活 24 小时。MLung 血流量为 716 ± 227 mL/min。出口氧饱和度为 98.3 ± 2.6%。活化凝血时间为 151±24 秒。血小板计数在 24 小时内从 334,333 ± 112,225 下降到 123,667 ± 7,637。血浆游离血红蛋白和白细胞和血小板活化没有显着变化。

结论

NOSA 系统以与天然血管内皮相似的速率提供穿过无泵人工肺气体交换膜的 NO 通量，并实现人工肺回路 24 小时的有效局部抗凝。