Bridge to neonatal Fontan repair of single ventricle

描述（由申请人提供）： 我们提出了一项高风险/高影响的研究，以开发一种创新的循环支持策略，使用植入式泵治疗单功能心室。最常见的形式是左心发育不全综合征，其中左心室无法以功能性的方式形成，是生命第一年内所有出生缺陷死亡的主要原因。目前，外科修复是通过三个单独的手术进行的。在第一次手术中，流向肺部的血流必须来自全身肺动脉分流，以克服新生儿肺血管阻力可能升高。然而，分流使这种手术因不稳定和死亡率而臭名昭著。在第二次和第三次手术中，分流器被断开，通过将腔静脉连接到肺动脉来实现血液流向肺部。稳定性和生存能力大大提高。不幸的是，由于通过反应性肺循环实现被动血流的障碍尚未解决，第二和第三个程序不能在新生儿中安全地进行。我们提出了一个独特的应用血泵暂时增加流量从大静脉通过肺部，直到潜在的反应解决。这一过程通常在2周时发生得最快，在8周时几乎完成。避免了有问题的分流，新生儿肺血管由来自体静脉源的低压、高容量血流灌注，类似于正常的右心室血流动力学。我们假设在这些条件下，新生儿肺动脉将正常成熟。一旦过渡性肺血管系统充分重塑，允许全身静脉源被动灌注肺，就可以安全地移除泵。我们进一步假设，新生儿将耐受允许被动静脉血流通过肺部所需的体静脉压升高。使用新生儿单心室循环动物模型，我们将通过以下具体目标来测试这些假设：将辅助单心室循环（腔静脉泵+体循环心室）转换为无辅助单心室循环，其中肺仅由被动腔静脉流灌注。我们已经生成了试验数据，支持使用当前可用技术的这种创新技术的可行性。我们期望这种方法的成功完成将把目前高风险的三阶段手术策略转换为更安全的单阶段范例，即单心室心脏病的新生儿Fontan姑息治疗。

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.