HETEROTOPIC TRANSPLANTATION OF THE IMMATURE HEART

未成熟心脏的异位移植

• 批准号: 3355170
• 负责人: EDWARD Donald VERRIER
• 金额: $ 29.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355170
• 关键词: anencephalus; atherosclerosis; congenital heart disorder; cyclosporines; echocardiography; growth /development; heart circulation; heart function; heart transplantation; immature animal; immunosuppression; magnetic resonance imaging; prednisone; radionuclide imaging /scanning; radiotracer; swine; tissue donors; xenotransplantation

Many children currently born with complex congenital heart disease cannot be adequately palliated by existing surgical techniques. Such lesions include variants of hypoplastic left or right heart syndrome and single ventricle. These children may have a potentially full life restored by transplantation but the optimal method of transplantation (orthotopic versus heterotopic) particularly in young infants is not known. The technical problems with small size, functional immaturity and adaptation, long-term graft survival, growth and optimal methods of immunosuppression must be addressed experimentally in appropriate fetal and neonatal models. At present the most limiting factor to clinical transplantation in children, particularly infants, is the availability of donor organs. We believe the use of vital organs from anencephalic fetuses may be a biologically superior, logistically simpler, and more cost effective solution. We also believe that soon the legal and ethical issues surrounding anencephalic donation will be favorably resolved. We have previously developed methods of using the fetal and neonatal heart as an auxiliary left heart bypass (left atrium to aorta) in immature pigs. We have refined our methods of harvest, preservation, anastomotic arrangement, and catheter placement for acute hemodynamic studies. This preparation can be done without the use of cardiopulmonary bypass, heparin, hypothermia, or circulatory arrest. We have achieved modest long-term survival (ten days) without immunosuppression. We now plan to use the immature pig model to 1) assess the relative output from the grafted and native heart using pressure transducers, electromagnetic flow probes, and radioactive microspheres, 2) determine the functional capacity of the neonatal donor heart to respond to acute manipulations of preload and afterload (using reversible occluders), 3) achieve long-term survival with immunosuppression, 4) to document growth, functional adaptation, and rejection, 5) to study chronic adaptation of the grafted heart to gradually increased functional demand produced by ameroid constrictor, and 6) to determine the best immunosuppression regimen to minimize the frequency and severity of rejection episodes and maximize growth of the immature animal.

许多孩子目前出生的先天性心脏 现有外科手术无法充分抑制疾病 技术。 这样的病变包括左或左侧的变体 右心综合症和单个心室。 这些孩子可以 通过移植恢复了潜在的充实生活，但是 最佳移植方法（原位与异位型） 尤其是在年轻的婴儿中尚不清楚。 技术 大小，功能不成熟和适应的问题， 长期移植生存，生长和最佳方法 免疫抑制必须在实验中解决 适当的胎儿和新生儿模型。 目前最多 限制儿童临床移植的因素，特别是 婴儿是供体器官的可用性。 我们相信使用 来自脑源胎儿的重要器官可能是生物学上的 优越，逻辑上更简单，更具成本效益的解决方案。 我们也相信很快的法律和道德问题 脑脑捐款将得到有利的解决。 我们以前已经开发了使用胎儿和 新生儿心脏作为辅助左心旁路（左心房 不成熟的猪中主动脉）。 我们已经完善了收获方法， 保存，吻合布置和导管放置 用于急性血液动力学研究。 可以做准备 不使用心肺旁路，肝素，体温过低， 或循环逮捕。 我们已经实现了谦虚的长期 生存（十天）没有免疫抑制。 我们现在计划 使用未成熟的猪模型1）评估来自 使用压力传感器的嫁接和天然心脏， 电磁流探针和放射性微球，2） 确定新生儿供体心脏的功能能力 响应预加载和后负载的急性操作（使用 可逆咬合者），3）实现长期生存 免疫抑制，4）记录生长，功能适应， 和拒绝，5）研究移植心脏的慢性适应 逐渐增加了由阿您生产的功能需求 收缩器和6）确定最佳免疫抑制 方案以最大程度地减少排斥的频率和严重程度 发作并最大化未成熟动物的生长。