Bridge to neonatal Fontan repair of single ventricle

新生儿单心室 Fontan 修复术的桥梁

• 批准号: 6907467
• 负责人: MARK D RODEFELD
• 金额: $ 21.93万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6907467
• 关键词: auxiliary heart prosthesis; cardiovascular disorder therapy; circulatory assist; congenital heart disorder; disease /disorder model; health care quality; heart surgery; heart ventricle; hemodynamics; medical implant science; method development; newborn animals; newborn human (0-6 weeks); nonhuman therapy evaluation; prognosis; pulmonary artery; pulmonary circulation; sheep; veins

DESCRIPTION (provided by applicant): We propose a high risk/high impact study to develop an innovative circulatory support strategy using an implantable pump for the treatment of single functional ventricle. The most common form, hypoplastic left heart syndrome, in which the left ventricle fails to form in a way that is ever functional, is the leading cause of death from all birth defects in the first year of life. Currently, surgical repair is performed with three separate operations. In the first operation, blood flow to the lungs must be derived from a systemic-to-pulmonary arterial shunt to overcome the potentially elevated newborn pulmonary vascular resistance. The shunt, however, makes this procedure notorious for instability and mortality. In the second and third operations, the shunt is disconnected, and blood flow to the lungs is accomplished by connecting the vena cava to the pulmonary arteries. Stability and survival are greatly improved. Unfortunately, the second and third procedures cannot be safely performed in the newborn due to the unsolved obstacle of achieving passive blood flow through the reactive pulmonary circulation. We propose a unique application of a blood pump to temporarily augment flow from the great veins through the lungs until the potential for reactivity resolves. This process normally occurs most rapidly by 2 weeks and is nearly complete at 8 weeks of life. The problematic shunt is avoided, and the newborn pulmonary vessels are perfused by a low-pressure, high-volume flow from a systemic venous source similar to normal right ventricular hemodynamics. We hypothesize that under these conditions, the neonatal pulmonary arteries will mature normally. Once the transitional pulmonary vasculature has remodeled sufficiently to permit a systemic venous source to perfuse the lungs passively, the pump can be safely removed. We further hypothesize that the neonate will tolerate the systemic venous pressure elevation required to permit passive venous flow through the lungs. Using a newborn animal model of univentricular circulation, we will test these hypotheses through the following specific aim: To transition an assisted univentricular circulation (cavopulmonary pump + systemic ventricle) to an unassisted univentricular circulation in which the lungs are perfused by passive vena caval flow alone. We have generated pilot data which support feasibility of this innovative technique using currently available technology. We expect that successful completion of this approach will convert the current high risk three-stage surgical strategy to a much safer single-stage paradigm of newborn Fontan palliation of single ventricle cardiac disease.

描述（由申请人提供）： 我们提出了一项高风险/高影响研究，以使用可植入的泵来制定创新的循环支持策略，以治疗单个功能性心室。最常见的形式是左心室综合症，左心室无法以实用的方式形成，是生命第一年所有出生缺陷的主要死亡原因。当前，手术维修是通过三个单独的手术进行的。在第一次手术中，必须从全身性的动脉分流中衍生出血液流向肺部，以克服潜在升高的新生儿肺血管耐药性。但是，分流器以不稳定和死亡率臭名昭著。在第二和第三个手术中，分流器断开，并通过将静脉腔连接到肺动脉来完成流向肺部的血流。稳定性和生存率大大提高。不幸的是，由于无法解决通过反应性肺循环的被动血流的未解决障碍，因此无法在新生儿中安全执行第二个和第三个程序。我们提出了血泵独特的应用，以暂时增加从大静脉通过肺部的流动，直到反应性消退为止。这个过程通常在2周之前最快地发生，并且在生命的8周时几乎完成。避免了有问题的分流器，新生儿肺部血管通过与正常右心室血液动力学类似的全身静脉源的低压，高体积流量灌注。我们假设在这些条件下，新生儿肺动脉正常成熟。一旦过渡性肺脉管系统进行了充分的重塑以使系统的静脉源可以被动地灌注肺，便可以安全地除去泵。我们进一步假设，新生儿将忍受允许被动静脉流穿过肺所需的系统性静脉压力高度。我们将使用一个新生动物的单脑膜循环模型，通过以下特定目的测试这些假设：过渡辅助的单脑室循环（Cavopulonary Pump +全身性心室），以单独使用的单脑室循环，在该循环中，单独用无动物静脉腔流灌注肺。我们已经生成了使用当前可用技术的创新技术可行性的试点数据。我们预计，这种方法的成功完成将把当前的高风险三阶段外科手术策略转变为单个心室心脏病的新生儿fontan palliation的更安全的单阶段范式。