Investigation of a chronic single-stage sheep Fontan model

John M. Kelly MD , Zinan Hu BS , Felipe Takaesu BS , Tatsuya Watanabe MD, PhD , Judd Storrs PhD , Benjamin Blais MD , Satoshi Yuhara MD , Adrienne Morrison BA , Kirsten Nelson BA , Anudari Ulziibayar MD , Eric Heuer BA , Cole Anderson BS , Michael Jimenez BA , Joseph Leland BA , Raphael Malbrue DVM , Carmen Arsuaga-Zorrilla DVM, MS , Laurie Goodchild DVM , Aymen Naguib MD , Christopher McKee MD , Jordan Varner BA , Christopher K. Breuer MD
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Abstract

Objectives

Our goal was to conduct a hemodynamic analysis of a novel animal model of Fontan physiology. Poor late-term outcomes in Fontan patients are believed to arise from Fontan-induced hemodynamics, but the mechanisms remain poorly understood. Recent advances in surgical experimentation have resulted in the development of a chronic sheep model of Fontan physiology; however, detailed analysis of this model is lacking.

Methods

We created a single-stage Fontan model in juvenile sheep with normal biventricular circulation. The superior vena cava was anastomosed to the main pulmonary artery, and the inferior vena cava was connected to the main pulmonary artery using an expanded polytetrafluoroethylene conduit. Longitudinal hemodynamics, including catheterization and magnetic resonance imaging were evaluated.

Results

Four out of 12 animals survived, with the longest surviving animal living 3 years after single-stage Fontan. We showed a significant era effect regarding survival (1 out of 8 and subsequently 3 out of 4 animals surviving beyond 2 months) attributed in large part to the procedural learning curve. Key characteristics of Fontan hemodynamics, namely systemic venous hypertension and low normal cardiac output, were observed. However, recapitulation of passive human Fontan hemodynamics is affected by volume loading of the right ventricle given an anatomic difference in sheep azygous venous anatomy draining to the coronary sinus.

Conclusions

A significant learning curve exists to ensure long-term survival and future surgical modifications, including banding of the main pulmonary artery and ligation of the azygous to coronary sinus connection are promising strategies to improve the fidelity of model hemodynamics.
慢性单段绵羊丰坦模型的研究
我们的目标是对一种新型的丰坦生理学动物模型进行血液动力学分析。人们认为,Fontan患者的晚期不良预后是由Fontan引起的血流动力学因素造成的,但人们对其机制仍然知之甚少。最近的手术实验进展导致了慢性绵羊丰坦生理学模型的建立;然而,目前还缺乏对该模型的详细分析。方法我们在具有正常双心室循环的幼年绵羊中建立了单期丰坦模型。上腔静脉与主肺动脉吻合,下腔静脉通过膨体聚四氟乙烯导管与主肺动脉相连。结果 12只动物中有4只存活,其中存活时间最长的动物在单期丰坦术后存活了3年。我们发现在存活率方面存在明显的时代效应(8 只动物中有 1 只存活超过 2 个月,随后 4 只动物中有 3 只存活超过 2 个月),这在很大程度上归因于手术学习曲线。我们观察到了丰坦血液动力学的主要特征,即全身静脉高压和低正常心输出量。结论 为确保长期存活,存在着显著的学习曲线,而未来的手术修改,包括主肺动脉的捆扎和绵羊紫绀至冠状窦连接的结扎,都是提高模型血液动力学真实性的有前途的策略。
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CiteScore
1.70
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