【作者】 董爱强；

【导师】 陈如坤；

【作者基本信息】 浙江大学 ， 外科学， 2002， 博士

【摘要】 新型人造心脏瓣膜——全热解碳双叶瓣是与上海九凌冶炼公司合作，于1995年初研制的第三代人造心脏瓣膜。它有别与St．Jude瓣和CarboMedics瓣等目前临床上常用的进口双叶瓣，它的瓣架和瓣阀均由热解碳一种材料制成的(无基体)，而后者是石墨基体外热解碳涂层的。先前的体外测试结果表明，该新型人造瓣膜经久耐磨，有效瓣口面积较大，人造瓣的跨瓣压差小，具有良好的流体动力学特性。本研究即按照GB12279-90和ISO5840-96(E)人造心脏瓣膜测试要求，对新型全热解碳双叶瓣进行动物植入研究和临床植入研究，为临床应用提供科学依据。 一．动物植入研究 材料与方法：健康羊15只，气管插管、全身麻醉，颈内静脉插Swan-Ganz导管。采用标准的体外循环方法行二尖瓣置换手术，植入21mm新型人造瓣。术后肝素抗凝3个月。选 Pi以d 一 择与人造瓣匹配较好的6只羊，术中在体外循环结柬后，直视下用双导管法直接测定左房 压（Pod、左室压OLV），计算跨瓣压差；同时用热稀释法测定该时的心排量（CO）等血流动力 学参数。 长期存活的羊分批于术后1周、12周、30个月处死。所有动物都作尸检，检查人造 瓣膜有无坏损，房、室面人造瓣膜上有无血栓形成，解剖心、肺、肝、脾、肾、大脑等脏 器有无栓塞现象。2只羊在术后30个月行心脏超声检查，观察人造瓣膜在体内的状况， 有无瓣周漏及血栓形成等，并测定羊的心排量和跨瓣压差等。再次全麻、开胸，直视下用 双导管法直接测定左房压p、左室压oLV），得出跨瓣压差，同时测定该时的心排量（C） 等（方法和仪器同前）。然后用多巴酚丁胺负荷试验模拟动物的运动状况，在模拟运动状 况 F测定瓣膜的血流动力学参数。多巴酚厂胺剂量 stwin—I0twin～ 20uglkg／ffiin，每隔 15分钟增加剂量，分别测定不同剂量多巴酚丁胺导致血压、心率、心 排量等变化下的P。、P。、等参数，评价人造瓣膜在运动状况下的血流动力学性能。 结果：5只羊术后24h内死亡，5只2448h死亡，另5只长期存活，生长良好，体重增 加。手术死亡均与人造瓣膜本身无关，主要手术死亡原因是羊的二尖瓣环与人造瓣膜大小 不匹配引起瓣环撕裂、急性心衰而死亡。尸检见人造瓣无坏损，机械性能良好；心腔内无 血栓形成，肺、肝、脾、肾、脑等脏器的大体检查和病理切片均无栓塞的证据：心内膜光 滑，无人造瓣膜心内膜炎的征象。术中导管测得的跨瓣压差为5．2土1．7mmHg，术后30个 月导管测得静息下的跨溶压差为6．l土0．3mlnHg。模拟运动状况下，随多巴酚丁胺剂量的 增大，心排量（CO）明显增加，而跨瓣压差随CO的明显增加仅轻度增大。心超测定的跨瓣 压差为 6．8土0．4mlnHg，与用导管法直接测得的跨瓣压差非常接近。实验表明该瓣膜的跨 瓣压差较小，血流动力学性能良好。 二．屹床桓入扭究 2 P｝Vt 一 材料与方法：全组62例病人，男性24例，女性38例，年龄2M2岁，病史2－26年。 以风湿性心脏病为主，共56例；二尖瓣退行性变3例：感染性心内膜炎伴主动脉瓣、二 尖瓣病变各1例；先天性主动脉瓣畸形、重度主动脉溶狭窄伴外露性钙化1例。房颤心律 33例，左心房血栓10例，们瘫4例。术前心功能mWn）m级27例，w级35例。 在体外循环下行瓣膜置换手术，共植入新型人造心脏瓣膜 74只，其中 AVRll例， MTh 39例，DTh 12例。同朋手术有：先天性缺损修补术 3例，Cox迷宫Ill型手术 4例， 左室减容术oL叮加二尖勇成形术po）l例，巨大左心房折叠术14例，左房血栓清除术 ！0例，三尖泌成形术厂w怔5例．术后均接受WNn抗凝治疗，并将病人随机分为常 规抗凝强度组（INRI．63Af．30）和低抗凝强度组（INR．3oil．63）。 结果：全组62例，无手术死亡；全部获得定期随访，随访】4－72个月，总随访1920病 人．月，平均 31个月，62例均长期存活；手术 1年后心功能均从术前的Ill—IV级转为 1级， 其中35例术后半年转为1级，可不同程度的体力劳动，生活质量良好；未发生瓣膜结构 衰坏、人造瓣膜心内膜炎等并发症。术后3—8个月均作有关溶血化验，AVR、MVR、DVR 三组病例LDH都偏高，但血红蛋白、血小板计数和总胆红素均正常，在临床上未引起明 显的溶血和溶血性贫血。接受不同抗凝强度治疗的两组病人，均未发生血栓形成和血栓栓 塞并发症，但低抗凝强度组病人无抗凝出血，而常规抗凝强度组有3例小的出血事件。 11例 AVR分别在更多还原

【Abstract】 The new type of cardiac valve prosthesis is a low profile, bileaflet mechanical prosthesis with three flow orifices. Differing from other mechanical prosthetic valves, such as St. Jude and CarboMedics valve prostheses, coated with pyrolytic carbon, this new valve prosthesis is constructed entirely with pyrolytic carbon. In vitro studies have consistently demonstrated theoretical safety and superior hemodynamic performance. In vivo study was performed in accordance with the requirements recommended by the ISO 5840-96(E) and GB 12279-90 for testing of prosthetic valves, so as to evaluate the durability, hemodynamic performance, and biocompatibility of the prosthesis.1. Animal testMaterials and Methods: Fifteen sheep weighted about 50kg underwent mitral valve replacement with 21mm new cardiac valve prostheses under endotracheal anesthesia. Standard methods of cardiopulmonary bypass were utilized. Heparin was used in 3months since operation. Open cardiac catheterization was performed in six animalsafter mitral valve replacement. Left atrial pressure (PLA) and left ventricular pressure (PLv) were measured simultaneously by dual-catheter technique. Cardiac output (CO) was determined by thermodilution technique.Animals were put to death at 1,12 weeks and in 30 months postoperatively by barbiturate overdose following systemic heparinization. The heart, lungs and peripheral organs including the liver, spleen and kidney were excised and examined grossly to determine if thromboembolic phenomenon occurred. The hearts were examined to observe the new endocardium on the left atrial side and the left ventricular side of the valve. Photographs of atrial and ventricular view of the prosthesis were performed. The new endocardium was subjected to electron microscopic examination. Doppler echocardiography was performed in two sheep 30 months after implantation to measure CO and transvalvular gradients and to determine if thrombosis or paravalvular leakage occurred. The second open cardiac catheterization was performed to determinate the PLA. PLV and so on. CO was measured by thermodilution technique. The hemodynamic performance of the new cardiac prosthesis was evaluated by means of dobutamine stress catheterization technique. Dobutamine was administrated at the rate of 5ug ’kg’1 fmin~1 with the dose increased every 15 minutes. PLA, PLV and CO were measured under different dobutamine doses stress, respectively. Results: 5 sheep died within 24hr after operation, 5 sheep died during 24-48hr, 5 sheep survived. 5 of the 10 deaths resulted from the anulus tore. There was no evidence of embolic phenomenon, nor were there any mechanical valve failures. The transvalvular gradients were 5.2 + 1. 7mmHg during operation, and 6.1?.3mmHg 30 months after implantation respectively. There was a minimal increase in transvalvular gradient as CO7increased under different dobutamine doses stress. Transvalvular gradients were 6.8 + 0. 4mmHg measured by echocardiography, similar to the invasive gradients. 2. Clinical trialMaterials and Methods: Between January, 1996 and January, 2002,62 patients underwent valve replacement with the new type of prosthetic valves. Of the 62 patients, 24 were male and 38 female. The subjects ranged in age 20?2 years. The medical history ranged 2~26 years. Rheumatic valvular disease was the predominant lesion in 56 patients, mitral valve prolapse in 3 patients, infective endocarditis associated with MI or AI respectively in 2, Congenital valvular disease in 1 patient. Of these patients, 33 were associated with atrial fibrillation, 10 with left atrial thrombus, and 4 with hemiplegia. Preoperative functional status was 27 in class III(NYHA) and 35 in class IV.The surgical technique was similar in each case, standard cardiopulmonary bypass techniques were utilized. Of the 62 patients, 11 had AYR, 39 had MVR, and 12 had DVR. Associated procedures were performed, these included repair of congenital defect in 3 patients, the Cox Maz III procedure for treatment of atrial fibrillation i更多还原