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. 2022 Feb;13(1):181-190.
doi: 10.1007/s13239-021-00563-6. Epub 2021 Jul 14.

Establishing Background Pathologic Changes of Valve Replacement Surgery in Sheep

Jill T Schappa Faustich  1 , John P Carney  2 , Matthew T Lahti  1 , Benjamin L Zhang  1 , Richard W Bianco  1
Affiliations

Establishing Background Pathologic Changes of Valve Replacement Surgery in Sheep

Jill T Schappa Faustich et al. Cardiovasc Eng Technol. 2022 Feb.

Abstract

Purpose: Sheep are the standard preclinical model for assessing safety of novel replacement heart valves, yet the anatomic and pathologic effects of invasive surgery, including those involving cardiopulmonary bypass (CPB), are unknown. Thus, we aimed to determine the gross, hematologic and biochemical effects of sham mitral and aortic replacement valve procedures in sheep to establish a useful control for evaluation of novel replacement valves.

Methods: Six control sheep were examined without any surgical intervention. Six sham mitral valve replacements (MVR) and six sham aortic valve replacements (AVR) were performed on 12 sheep. Complete blood counts and serum biochemistry were performed throughout the study. Sheep were sacrificed with a necropsy performed at 90 days.

Results: Renal infarcts (RIs) were the most frequently observed lesion, averaging 4.7 in control sheep, 2.5 with MVR and 5.8 with AVR. The number of infarcts strongly correlated with total estimated area of infarcted kidney (r = .84, p < .01). Additional cardiac interventions were significantly correlated with increased numbers of RIs (r = .85, p < .01). There was no correlation between number of RIs and time on CPB, or between AVR and MVR procedures.

Conclusion: The sheep model for AVR and MVR requires invasive surgery and CPB, which are associated with background anatomic and pathologic changes, especially in cases with additional surgical cardiac interventions. These findings serve as a critical control for future evaluation and development of novel replacement valves in order to distinguish device-related safety issues from expected outcomes of the surgical procedure and normal background changes in sheep.

Keywords: Animal model; Cardiopulmonary bypass; Preclinical; Renal infarcts; Sheep; Valve replacement surgery.

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Figures

Figure 1
Figure 1
(a) Gross pathology of renal infarcts. Note well-demarcated depressed round regions of pale tan to white tissue (white arrows). (b) Histopathology of the gross lesion in (a) demonstrating wedge-shaped regions of inflammatory cell infiltration (predominantly lymphocytes with fewer plasma cells and occasional macrophages) and mild fibrosis (white arrows).
Figure 2
Figure 2
Representative histology of renal infarcts. Histology from MVR group animals 3 (a, b) and 6 (c, d) and AVR group animals 10 (e, f) and 12 (g, h). Multifocally throughout the renal cortex, renal tubules are surrounded by infiltrates of lymphocytes, plasma cells, and histiocytes and low numbers of extravasated erythrocytes (hemorrhage), as outlined by white arrows (a, b, e), white circles (c, d, g), and a white triangle in image h. The entire area represented in image f is affected.
See this image and copyright information in PMC

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