Back to the root: a large animal model of the Ross procedure

Abstract

The excellent clinical outcome of the Ross procedure and previous histological studies suggest that the pulmonary autograft has the potential to offer young patients a permanent solution to aortic valve disease.We aim to study the early mechanobiological adaptation of the autograft. To this end, we have reviewed relevant existing animal models, including the canine models which enabled Donald N Ross to perform the first Ross procedure in a patient in 1967. Two research groups recently evaluated the isolated effect of systemic pressures on pulmonary arterial tissue in an ovine model of a pulmonary artery interposition graft in the descending aorta. While this model is ideal to study the artery's biological response and the effect of external support, it does not recreate the complex environment of the aortic root. The freestanding Ross procedure has been performed in pigs and sheep before. These studies offered valuable insights into leaflet growth and histological remodeling, yet may be less relevant to adults undergoing the Ross procedure, as pronounced autograft dilatation was achieved by using small, rapidly growing animals. Therefore, a large animal model remains needed to determine the ideal conditions and surgical technique to ensure longterm autograft remodeling and valve function. We set out to develop an ovine model of the Ross procedure performed as a freestanding root replacement, acknowledging that the sheep's specific anatomy and the setting of an animal laboratory would mandate several modifications in surgical strategy. This article describes the development, surgical technique and early outcomes of our animal model while highlighting opportunities for further research.

Understanding Pulmonary Autograft Remodeling After the Ross Procedure: Stick to the Facts

“…In a similar animal model using resorbable external support, 123). (123). Preliminary histological evaluation is consistent with previous clinical and experimental explant studies (Figure 6).…”

“…In vitro culture of a pulmonary artery in a bioreactor may provide valuable insights into the timeline of early remodeling and the role of shear stress, pre-stretch at implantation and acute hypertension. Large animal models also hold great promise to evaluate whether current strategies to prevent dilatation—external support and antihypertensive treatment—promote remodeling, either by modifying the mechanical environment or by interfering with molecular pathways ( 123 ). To assess whether the autograft remains viable—capable of healing and regulating its mechanical properties—active mechanical testing of freshly explanted leaflets and wall would be required ( 162 ).…”

“…Unfortunately, they did not investigate the dilated autograft wall or ECM remodeling of the valve ( 122 ). Our group recently developed an ovine model of the Ross procedure performed as a freestanding root replacement ( 123 ). Preliminary histological evaluation is consistent with previous clinical and experimental explant studies ( Figure 6 ).…”

“…Overview of animal models relevant to the Ross procedure with main findings(22,26,84,(118)(119)(120)(121)(122)(123)(124).…”

Drivers of Vascular Growth and Remodeling: A Computational Framework to Promote Benign Adaptation in the Ross Procedure

“…Despite a reduction in arterial wall dilation and therefore preservation of valve function, it turns out that a permanent textile wrapping can lead to excessive stress-shielding phenomena [11]. Experimental animal trials of a polymeric reinforcement around the autograft have shown thinning of the vessel wall, smooth muscle cell death, and loss of wall mechanical compliance [12,13,14]. A permanently present external support can prevent dilatation and tissue failure after surgery, but it inhibits important arterial wall compliance.…”