心脏移植长期存活受者免疫抑制治疗经验总结

Long-term survival of heart transplant recipients: experience summary of immunosupressive therapy

目的总结并分析4例存活时间在16年以上的心脏移植受者免疫抑制治疗经验。方法回顾性分析哈尔滨医科大学附属第二医院心外科1992年4月至2000年1月施行的4例原位心脏移植临床资料,重点分析受者免疫抑制治疗经过。4例供者均为脑死亡器官捐献,供心采用改良St.Thomas液保存。1例受者原发病为慢性克山病,3例为扩张性心肌病。3例受者采用标准法心脏移植,1例采用全心法心脏移植。术后均采用环孢素+糖皮质激素+硫唑嘌呤三联免疫抑制方案,免疫维持治疗单用环孢素。随访期间监测环孢素血药浓度、外周血白细胞计数及淋巴细胞功能,行心电图、X线胸片、超声心动图、冠状动脉造影、光学相干断层扫描(OCT)及心内膜下心肌活检等检查。若受者出现排斥反应则采用冲击治疗或改用其他免疫抑制剂。结果截至2016年6月,3例受者存活,1例受者死亡。3例存活受者存活时间分别为22年4个月、20年7个月和16年5个月,1例死亡受者术后18年6个月死于多器官功能衰竭。4例受者术后10年内分别发生排斥反应1~6次,采用冲击治疗后均恢复。3例存活受者术后第10年环孢素剂量调整为0.5~1.0 mg·kg^(-1)·d^(-1)。4例受者术后10年内冠状动脉造影检查均未发现冠状动脉血管病变。2009年5月,3例存活受者冠状动脉造影和OCT检查示1例受者冠状动脉仅见斑块浸润,自觉症状良好,该受者2015年5月冠状动脉造影及OCT检查结果示冠状动脉多处狭窄,遂行支架治疗,其余2例受者检查结果均正常。结论心脏移植术后及时、准确地诊断排斥反应,合理、正确地调整免疫抑制治疗方案,个体化免疫治疗用药和积极、有效控制并发症是受者长期存活的重要手段。

Objective Summary and analysis the experience of immunosuppressive therapy of 4 recipients who survived over 16 years after heart transplantation. Methods The clinical data of 4 heart transplant recipients in the Second Affiliated Hospital of Harbin Medical University during April 1992 and January 2000 was analyzed retrospectively, which mainly focusing on the treatment experience of immunosuppressive therapy. Four donors were all donation after brain death and donor organs were preserved by improved St. Thomas fluid. The protopathys of recipients were chronic keshan disease （1 case） and dilated cardiomyopathy （3 cases）, respectively. The methods of heart transplantation were standard anastomosis （3 cases） and whole-heart （1 case）. The immunosuppressive treatment protocol after operation was eielosporin ＋ azathioprine ＋ glucoeorticoid and cielosporin was used for immunosuppressive maintenance therapy. Blood concentration of ciclosporin, periphery white blood count and lymphocyte function were monitored during follow-up. Electrocardiogram, chest X-ray plain film, ultrasonic cardiogram, coronary arteriography, optical coherence tomography （OCT） and endomyocardial biopsy were also did during follow-up. Implosive therapy or immunosuppressive agent replacement therapy was used when rejection occured. Results Three recipients survived and 1 recipient died until June 2016. The survival time of the 3 survivors was 22 years and 4 months, 20 years and 7 months, 16 years and 5 months, respectively. The dead recipient died of multiple organ failure 18 years and 6 months after operation. Four recipients occured rejection 1 to 6 times during 10 years after operation and all recoverd after implosive therapy. The dose of ciclosporin for 3 survivors adjusted to 0.5 - 1.0 mg · kg^-1 · d^-1 at 10 years after operation. All the recipients showed no coronary artery lesion during 10 years after operation. Three recipients recieved coronary arteriography and OCT in May 2009, and 1 recipient showed plaques infiltration and did not feel any uncomfortable, but the test results of coronary arteriography and OCT of this recipient in May 2015 showed that coronary artery stenosis was found and then stent placement was did. Test results of other two recipients were normal. Conclusions Diagnosis of rejection timely and accurately, adjusting immunosuppressive treatment plan reasonably, individualized immunosuppressive therapy and preventing the complication actively and effectively were helpful to improve long-term survival for heart transplantation recipients.