In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric Flow Conditions: A Benchmark Study
In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric Flow Conditions: A Benchmark Study
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DOI：
10.1111/aor.13165
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发表时间：
2018-11-01
影响因子：
2.4
通讯作者：
Adachi, Iki
中科院分区：
文献类型：
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作者：
Chan, Chris Hoi Houng;Diab, Sara;Adachi, Iki
儿童心室辅助装置（VAD）的开发明显落后于成人装置。这种令人沮丧的现实反映在以下事实中：柏林心脏EXCOR VAD是目前美国唯一获批的儿科专用器械。另一种选择是标签外使用成人连续流VAD，如HeartMate II（HMII），这不可避免地会导致儿童患者-器械尺寸不匹配。我们试图在儿科血流条件下进行体外血液相容性试验，具体目的是为未来的儿科器械开发提供基准值。鉴于上述事实，即脉动装置和连续流动装置均用于儿科人群，我们选择在本研究中测试这两种类型的装置。在恒定血流动力学条件下（流速，Q = 2.5 +/-0.25 L/min;泵压差，Δ P = 68 +/-5 mm Hg），使用牛血测试EXCOR和HM II血泵。通过Harboe试验测量溶血。在体外试验期间，血浆游离血红蛋白稳定增加，EXCOR（P < 0.0001）和HM II（P <0.001）在5分钟和360分钟之间具有统计学显著差异。然而，血浆游离血红蛋白的增加程度与HMII相比更为显著（P < 0.001）。EXCOR和HM II的标准化溶血指数分别为0.003 +/-0.0026 g/100 L和0.085 +/-0.0119 g/100 L。使用流式细胞术通过CAPP 2A抗体检测的血小板活化也稳定增加，两种装置在5分钟和360分钟之间具有统计学显著差异（P < 0.05）。两种器械的血小板活化增加程度相似（P = 0.218）。通过免疫印迹法测量的高分子量血管性血友病因子（HMW vWF）多聚体降解在两种器械中均明显，但EXCOR的降解更为明显。所有三个时间点（120、240和360 min）的EXCOR血液样本与基线（5 min）存在显著差异，而只有360 min样本与HM II基线存在显著差异。总之，我们观察到EXCOR和HM II之间血液相容性特征的相似性和差异，这两种器械均常用于儿科人群。我们预计，本研究中的基准值将有助于未来儿童VAD的发展。
Development of pediatric ventricular assist devices (VADs) has significantly lagged behind that of adult devices. This frustrating reality is reflected by the fact that the Berlin Heart EXCOR VAD is currently the only approved pediatric-specific device in the USA. An alternative option is an off-label use of adult continuous-flow VADs, such as HeartMate II (HMII), which inevitably causes patient-device size mismatch in small children. We sought to conduct in vitro hemocompatibility testing in a pediatric flow condition, with a specific aim to provide benchmark values for future pediatric device development. Given the aforementioned fact that both pulsatile and continuous-flow devices are being used in the pediatric population, we opted to test both types of devices in the present study. The EXCOR and HMII blood pumps were tested using bovine blood under constant hemodynamic conditions (flow rate, Q = 2.5 +/- 0.25L/min; differential pressure across the pump, Delta P = 68 +/- 5mm Hg). Hemolysis was measured by Harboe assay. There was a steady increase in plasma free hemoglobin during in vitro testing, with a statistically significant difference between 5 and 360 min for both EXCOR (P < 0.0001) and HMII (P < 0.001). However, the degree of an increase in plasma free hemoglobin was more significant with HMII (P < 0.001). Normalized index of hemolysis for EXCOR and HMII were 0.003 +/- 0.0026g/100 L and 0.085 +/- 0.0119g/100 L, respectively. There was also a steady increase in platelet activation detected by CAPP2A antibody using flow cytometry, with a statistically significant difference between 5 and 360 min for both devices (P < 0.05). The degree of an increase in platelet activation was similar between the two devices (P = 0.218). High molecular weight von Willebrand factor (HMW vWF) multimer degradation measured by immunoblotting was evident for both devices, however, it was more pronounced with the EXCOR. EXCOR blood samples from all three time points (120, 240, and 360 min) were significantly different from the baseline (5 min), whereas only 360 min samples had a significant difference from the baseline with the HMII. In conclusion, we have observed similarities and differences in hemocompatibility profiles between the EXCOR and HMII, both of which are commonly used in the pediatric population. We anticipate the benchmark values in the present study will facilitate future pediatric VAD development.