TEMPORARY VENTRICULAR ASSISTANCE W/ PORCINE CARDIAC XENOGRAFTS

使用猪心脏异种移植物进行临时心室辅助

• 批准号: 6116580
• 负责人: DAVID H ADAMS
• 金额: $ 6.7万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6116580
• 关键词: Mammalia; Primates; cardiovascular system; orphan disease /drug; surgery; transplantation; urinary tract

Post-cardiotomy cardiogenic shock is a significant clinical problem that will effect approximately 1% of all patients undergoing cardiac surgery this year. Experience with mechanical ventricular assistance in these patients at the Brigham and Women's Hospital as well as nationally has been very disappointing, and only approximately 25% of such patients supported with conventional technology will survive to discharge. We are very interested in pursuing the possibility of using genetically modified porcine xenografts to provide temporary cardiac support. Thus far, we have performed transplant surgeries on 11 baboons. Some animals received the heterotopic heart transplant and the others the kidney transplant from the transgenic pig donors to the baboons. The experiments are in progress and the data being generated from those experiments is under continuous evaluation. The initial phase of experiments will address the immunologic questions of graft rejection upon transplantation. These studies will utilize heterotopic transplants attached to an artery and vein in the neck of recipients treated with cyclosporine and leflunomide. Control animals will receive hearts from non-transgenic swine. In a separate experiment we plan to perform a small number of isolated heterotopic kidney grafts obtained from the same transgenic swine cardiac donor as a pilot for possible future research. Early results suggest that modified cardiac xenografts which

心脏切开术后心源性休克是一个重要的临床问题，今年将影响约 1% 接受心脏手术的患者。布莱根妇女医院以及全国范围内对这些患者进行机械心室辅助的经验非常令人失望，在接受传统技术支持的此类患者中，只有大约 25% 能够存活到出院。 我们对利用转基因猪异种移植物提供临时心脏支持的可能性非常感兴趣。 到目前为止，我们已经对11只狒狒进行了移植手术。 一些动物接受了异位心脏移植，另一些则接受了来自转基因猪供体的狒狒的肾脏移植。 实验正在进行中，并且正在持续评估这些实验生成的数据。 实验的初始阶段将解决移植时移植物排斥的免疫学问题。 这些研究将利用附着在接受环孢素和来氟米特治疗的受者颈部动脉和静脉上的异位移植物。 对照动物将接受来自非转基因猪的心脏。在一项单独的实验中，我们计划进行少量从同一转基因猪心脏供体获得的分离异位肾移植，作为未来可能研究的试点。 早期结果表明，改良的心脏异种移植物