The Biocompatibility Evaluation Of A Wearable Artifical Pump Lung

[Objective] To address the need for ambulatory partial respiratory/ cardiopulmonary support for patients with advanced heart/lung disease, an ultracompact integrated wearable artificial pump-lung (APL) device suitable for the paracorporeal placement has been developed. The purpose of the present study was to evaluate the biocompatibility performance of the APL device through long term survival animal experiments.[Methods] Animal model by surgically placing the APL device between the right atrium and pulmonary artery with a set of implanted cannulae as the APL group (n=5). The anticoagulation treatment was maintained by continuous heparin infusion with a targeted ACT from 150 to 180 seconds. The device speed was maintained in the range from 5000 to 6000 rpm to made the flow of device begin at 3.2L/min. Sham surgery sheep (n=3) without device implanted were used for control.The device flow, gas transfer data and plasma free hemoglobin were measured continuously. Hematological data, platelet activation and blood biochemistry for biocompatibility, comprehensive metabolic panel and end-organ functions were assessed twice a week. After 30 days, the sheep were euthanized for necropsy. The explanted devices were examined for gross thrombosis and by scan electronic microscopy (SEM) for cell deposition.[Results] According to the in vivo study, all involved sheep survived for 30 days. The APL devices were capable of delivering an oxygen transfer rate of 140-160 ml/min with the flow rate went down to 2.44+ 0.10 L/min from 3.28±0.08L/min. The oxygen saturation at device outlet can keep above 95%. There were not significant different between APL and sham sheep in both the creatine phosphokinase and lactate dehydrogenase which relevant to the surgical trauma. APL sheep had acute kidney dysfunction after surgery but can recover to normal in a week. No effects on liver were found in both groups during study. Hematocrit elevated up to 34.58±2.10% during the later of study. Meanwhile, plasma free hemoglobin, the number of leucocytes and ratio of neutrophils of APL sheep were higher than sham sheep. Surface P-selectin, which can be consider as the marker of platelets activation had no significant differences between APL and sham sheep. However, soluble P-selectin level of APL sheep was stayed in higher level than sham sheep during the whole study period. After termination, the necropsy and tissue section reports are normal. Most of the device flow path and membrane surface was visibly clean with only a few tiny blood clots. In SEM, the weft fibers were easy to be the nidus of platelets adhesion and aggregateion.[Conclusions] In summary, the new and optimized pump-lung device exhibited capability of providing partly respiratory and circulation support with excellent biocompatibility and long-term reliability and the potential for clinical use.