国产新型人造心脏瓣膜——全热解碳双叶瓣的研制和植入研究

STUDIES ON PREPARATION AND IMPLANTATION OF A NEWLY DOMESTIC-MADE SOLID PYROLYTIC CARBON BILEAFLET HEART VALVE PROSTHESIS

目的 :研制新型人造心脏瓣膜。方法 :在沉积炉流化床中试制无基体全热解碳材料并检测其品质。设计双叶式人造心脏瓣膜结构图形。将材料加工成元件并组装成瓣膜。对材料和瓣膜作理化性能和生物学测试。作二尖瓣置换术动物实验 ,分别用双导管法和超声法在静息状态和多巴酚丁胺负荷模拟运动状况下测定瓣膜血流动力学性能。作人造瓣膜替换术 ,术后患者接受华法令低强度抗凝。用双导管法和超声法测定瓣膜的血流动力学参数。对术后全部患者作长期随访检查和记录。结果 :研制材料符合无基体全热解碳品质。双叶瓣设计获国家专利。瓣膜孔口直径大于其他常用双叶瓣和单叶瓣。流体动力学测试与CarboMedics双叶瓣、国产C L单叶瓣相比 ,研制瓣跨瓣压差最低 ,有效瓣口面积最大。瓣膜疲劳试验在不小于 10kPa压力下 ,经过 380× 10 6次的循环 ,开启关闭正常 ,无飞片、碎裂、分层、剥离。关闭分数和泄漏分数均在 10 %以内。细胞毒性、致敏、全身毒性、血液相容性、皮内植入反应试验等生物学试验结果均符合国家标准。动物试验羊长期存活 ,其中临床及尸检均表明未发生与瓣膜有关的并发症 ,两只羊在术后 30个月超声心动图检查提示人造瓣返流量小 ,测定M 2 1的跨瓣压差低 ,为 0 .91± 0 .0 5kPa。临床 6 2例换瓣包括MVR39例 ,

Aim: To develop a new heart valve prosthesis. Method: The methods consisted of preparing solid pyrolytic carbon without substrate in fluid-bed of deposit stove and assaying its property, designing configuration of the bileaflet heart valve prosthesis, making prosthetic components and assembling them into the prosthesis, examining chemo-physiological and biological features of both the materials and valve, implanting the valve prosthesis into sheep's mitral position and testing hemodynamics of the valve with both bi-catheter method and echocardiography in the situations of rest and mimic motion after loading dobutamine respectively; and doing autopsies to all the sheeps either died during surgical operation or sacrificed, performing clinical studies of implanting the valve and low intensity anticoagulant therapy with warfarin postoperatively; and testing hemodynamics of the valve with both bi-catheter method and echocardiography. All patients were followed up regularly after operation to get clinical and examination materials. Result: The developed material was in line with the required property of solid pyrolytic carbon without substrate. The prosthesis was proved to have larger orifices in comparison with the valves available currently in market, and showed lowest cross-valvular pressure gradient. The valve had undergone 380 × 10 6 open-close cycles before finishing the durability test without dislocation, fragmentation, delamination or stripping. Close fraction and leakage fraction were both within 10%. All biological test results including cytotoxicity, sensitization, systemic toxicity, biocompatibility and intradermal implantation test were negative according to the national standard. Five experimental sheeps acquired long-term survival and were proved to have no prosthesis-related complications. Thirty months after operation, 2 sheeps showed low cross-valvular pressure gradient (0.91 ± 0.05 kPa) and back flow echocardiographically in mitral position. Sixty-two volunteer patients accepted valvular replacement with 74 prostheses in total, included 39 cases of MVR, 11 AVR and 12 MVR + AVR. All patients survived from the operation and long-term survival rate was 100% Up to now, the longest postoperative period is 66 months, the shortest longer than 4 months, 57 patients over 1 year, 53 patients over 2 years, with an average of 30.4 months. Patients survived over one year got improvement of heart function from NYHA III-IV to NYHA I. There were no prosthetic-related complications. Sixteen patients had had examinations on hemolysis and anaemia and neither hemolytic anaemia nor detectable hemolysis was found. No patient suffered from hemorrhage or thromboembolism during anticoagulation therapy. Hemodynamic studies showed low cross-valve pressure gradient and little back flow. Conclusion: The developed heart valve prosthesis had good biocompatibility, durability and hemodynamic properties. The middle and small size prostheses have relatively large inner orifice and offer a good match for those who have smaller body constitution but engage in a heavy physical labor.