Bridge to neonatal Fontan repair of single ventricle

新生儿单心室 Fontan 修复术的桥梁

• 批准号: 7033083
• 负责人: MARK D RODEFELD
• 金额: $ 17.9万
• 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 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7033083
• 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/高影响的研究，以开发一种使用植入式泵治疗单功能脑室的创新循环支持策略。最常见的形式是左心发育不全综合征，即左心室不能以一种永远正常的方式形成，是导致所有出生缺陷在出生第一年死亡的主要原因。目前，外科修复通过三种不同的手术进行。在第一次手术中，必须通过体肺分流来获得肺的血流量，以克服潜在的新生儿肺血管阻力升高。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，分流管被切断，血液通过连接下腔静脉和肺动脉来实现。稳定性和存活率大大提高。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，第二和第三次手术在新生儿身上不能安全进行。我们提出了一种独特的应用血泵，以暂时增加流量从大静脉通过肺部，直到潜在的反应性解决。这一过程通常在出生2周时发生得最快，在出生8周时几乎完成。避免了有问题的分流，新生的肺血管由类似于正常右室血流动力学的系统静脉来源的低压、高容量血流灌流。我们假设在这些条件下，新生儿的肺动脉将会正常成熟。一旦过渡肺血管充分重建，允许全身静脉来源被动地对肺进行灌流，就可以安全地取出泵。我们进一步假设，新生儿将能耐受全身静脉压升高，以允许被动静脉流经肺部。使用新生的单室循环动物模型，我们将通过以下特定目的来检验这些假说：将辅助单室循环(腔肺泵+体循环)过渡到非辅助单室循环，其中肺由被动腔静脉血流单独灌流。我们已经利用现有技术生成了试验数据，支持这一创新技术的可行性。我们预计，这一方法的成功完成将把目前的高风险三阶段手术策略转变为更安全的新生儿Fontan单心脏疾病姑息治疗的单期范例。

项目成果

Twenty-four hour cardiopulmonary stability in a model of assisted newborn Fontan circulation.

• DOI: 10.1016/j.athoracsur.2005.06.063
• 发表时间: 2006
• 期刊: The Annals of thoracic surgery
• 作者: Cynthia D. Myers;Kelly D. Mattix;R. Presson;P. Vijay;Domingo Maynes;K. Litwak;John W. Brown;M. Rodefeld

Cavopulmonary assist: (em)powering the univentricular fontan circulation.

• DOI: 10.1053/j.pcsu.2011.01.015
• 发表时间: 2011
• 期刊: Seminars in thoracic and cardiovascular surgery. Pediatric cardiac surgery annual
• 作者: Rodefeld MD;Frankel SH;Giridharan GA
• 通讯作者: Giridharan GA

Cavopulmonary assist for the univentricular Fontan circulation: von Kármán viscous impeller pump.

• DOI: 10.1016/j.jtcvs.2010.04.037
• 发表时间: 2010-09
• 期刊: JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
• 影响因子: 6
• 作者: Rodefeld, Mark D.;Coats, Brandon;Fisher, Travis;Giridharan, Guruprasad A.;Chen, Jun;Brown, John W.;Frankel, Steven H.
• 通讯作者: Frankel, Steven H.