Creation of the Fontan circulation in sheep: a survival model

Puyvelde, Joeri Van; Rega, Filip; Minami, Tomoyuki; Claus, Piet; Cools, Björn; Gewillig, Marc; Meyns, Bart

doi:10.1093/icvts/ivz022

Cited by 12 publications

(11 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the sake of completeness, it has to be mentioned that one abstract describing a successful long-term ovine model without MCS was recently reported with extracardiac TCPCs with a perioperative survival rate of 58%. 33…”

Section: Commentmentioning

confidence: 99%

Approaches to Establish Extracardiac Total Cavopulmonary Connections in Animal Models—A Review

Granegger

Valencia

Quandt

et al. 2019

World J Pediatr Congenit Heart Surg

View full text Add to dashboard Cite

BACKGROUND Long-term survival of patients with a single ventricle palliated with a Fontan procedure is still limited. No curative treatment options are available. To investigate the pathophysiology and potential treatment options, such as mechanical circulatory support (MCS), appropriate large animal models are required. The aim of this review was to analyze all full-text manuscripts presenting approaches for an extracardiac total cavopulmonary connection (TCPC) animal model to identify the feasibility and limitations in the acute and chronic setting. METHODS A literature search was performed for fulltext publications presenting large animal models with extracardiac TCPCs on Pubmed and Embase. Out of 454 reviewed papers, 23 manuscripts fulfilled the inclusion criteria. Surgical procedures were categorized and hemodynamic changes at the transition from the biventricular to the univentricular condition analyzed. RESULTS Surgical procedures varied especially regarding coronary venous flow handling and anatomic shape of the TCPC. In most studies (n = 14), the main pulmonary artery was clamped and the coronary venous flow redirected by additional surgical interventions. Only in five reports, the caval veins were connected to the right pulmonary artery to create a true TCPC shape, whereas in all others (n = 18), the veins were connected to the main pulmonary artery. An elevated pulmonary vascular resistance was identified as a limiting hemodynamic factor for TCPC completion in healthy animals. CONCLUSIONS A variety of acute TCPC animal models were successfully established with and without MCS, reflecting the most important hemodynamic features of a Fontan circulation; however, chronic animal models were not reported.

show abstract

Section: Commentmentioning

confidence: 99%

Approaches to Establish Extracardiac Total Cavopulmonary Connections in Animal Models—A Review

Granegger

Valencia

Quandt

et al. 2019

World J Pediatr Congenit Heart Surg

View full text Add to dashboard Cite

show abstract

“…Surgically generated models of CHD in sheep have, particularly, advanced our understanding of the developmental pathophysiology of outflow track obstruction. For example, they have revealed maladaptive changes that result in uncompensated right ventricular hypertrophy (RVH) and progress to heart failure (Montgomery et al, 1998), differences in miRNA expression profiles in compensated and uncompensated RVH, as well as the effects of failed repair (Johnson Kameny et al, 2019;Kameny et al, 2018;Van Puyvelde et al, 2019).…”

Section: Sheepmentioning

confidence: 99%

Mending a broken heart: In vitro, in vivo and in silico models of congenital heart disease

Rufaihah

Chen

Yap

et al. 2021

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Birth defects contribute to ∼0.3% of global infant mortality in the first month of life, and congenital heart disease (CHD) is the most common birth defect among newborns worldwide. Despite the significant impact on human health, most treatments available for this heterogenous group of disorders are palliative at best. For this reason, the complex process of cardiogenesis, governed by multiple interlinked and dose-dependent pathways, is well investigated. Tissue, animal and, more recently, computerized models of the developing heart have facilitated important discoveries that are helping us to understand the genetic, epigenetic and mechanobiological contributors to CHD aetiology. In this Review, we discuss the strengths and limitations of different models of normal and abnormal cardiogenesis, ranging from single-cell systems and 3D cardiac organoids, to small and large animals and organ-level computational models. These investigative tools have revealed a diversity of pathogenic mechanisms that contribute to CHD, including genetic pathways, epigenetic regulators and shear wall stresses, paving the way for new strategies for screening and non-surgical treatment of CHD. As we discuss in this Review, one of the most-valuable advances in recent years has been the creation of highly personalized platforms with which to study individual diseases in clinically relevant settings.

show abstract

“…Because of the difficulty in creating an animal model of Fontan failure, testing with physiologically relevant mock circulation loops mimicking the failing Fontan circulation may be considered. 6,7 Challenges to be overcome include the potential for inflow suction events of large devices in compliant and narrow venous channels, as well as the potential for inadvertent competing flows in the contralateral superior vena cava in complex anatomies with bilateral superior cavopulmonary connections. Ideally, the proposal by Lin and colleagues 4 would decrease central venous pressures while increasing pulmonary arterial flow to improve cardiac preload.Patient selection is paramount.…”

mentioning

confidence: 99%

Commentary: Mechanical support for the subpulmonary circulation of Fontan physiology—A step in the right direction

Broda

Adachi

2019

The Journal of Thoracic and Cardiovascular Surgery

View full text Add to dashboard Cite

The Fontan operation is one of the greatest milestones in medicine and has saved the lives of numerous children born with single-ventricle heart disease. 1 Fontan was among the first to notice the palliative, rather than curative, nature of the operation. The palliative nature stems from the unique characteristics of the Fontan circulation, the lack of a subpulmonary ventricle, which leads to a range of cardiac and noncardiac complications. It is becoming apparent that such a peculiar physiology is destined for, in the long term, a failure of the circulation (failing Fontan circulation). This challenging condition has a high incidence of mortality with limited therapeutic options. 2 In the hopes of ''normalizing'' the circulation, much effort has been expended to develop a method to reverse the ''pumpless'' subpulmonary hemodynamics. 3 A novel support system reported by Lin and colleagues 4 in this issue of the Journal is one such example. In their avant-garde concept, a percutaneously inserted multilumen cannula is coupled to a pump for subpulmonary assistance. The simple design allows the inflow lumen to draw flow from both caval veins while returning blood into the pulmonary arteries through separate, adjustable outflow cannulas. This strategy may not only provide downstream pressures gains but also minimize recirculation, which is a common concern for mechanical support for total cavopulmonary connection without compartmental separation of inflow and outflow ports. 5 Proof-of-concept studies by computational methods are a good first step. Prototype development and rigorous in vitro testing are typical next steps needed before clinical translation. Because of the difficulty in creating an animal model of Fontan failure, testing with physiologically relevant mock circulation loops mimicking the failing Fontan circulation may be considered. 6,7 Challenges to be overcome include the potential for inflow suction events of large devices in compliant and narrow venous channels, as well as the potential for inadvertent competing flows in the contralateral superior vena cava in complex anatomies with bilateral superior cavopulmonary connections. Ideally, the proposal by Lin and colleagues 4 would decrease central venous pressures while increasing pulmonary arterial flow to improve cardiac preload.Patient selection is paramount. A major phenotype of failing Fontan circulation is systemic ventricular dysfunction, which can be supported well with a systemic ventricular assist device. 8 When used appropriately, this type of support carries a high success rate, as evidenced by 95% 6-month survival. 9 The concept of subpulmonary support would be relevant to a distinctly different phenotype, one that is characterized by flow limitation primarily in the pulmonary circulation. This phenotypic subset is more challenging for mechanical support, with only few sporadic reports of successful clinical cases and likely many more unreported failed attempts. 10 This is the aspect that makes the study described by Lin and colleagues 4 i...

show abstract

Creation of the Fontan circulation in sheep: a survival model

Cited by 12 publications

References 25 publications

Approaches to Establish Extracardiac Total Cavopulmonary Connections in Animal Models—A Review

Approaches to Establish Extracardiac Total Cavopulmonary Connections in Animal Models—A Review

Mending a broken heart: In vitro, in vivo and in silico models of congenital heart disease

Commentary: Mechanical support for the subpulmonary circulation of Fontan physiology—A step in the right direction

Contact Info

Product

Resources

About