Establishment of adult right ventricle failure in ovine using a graded, animal-specific pulmonary artery constriction model.

Michael Nguyen-Truong,June Boon,Jeremiah Easley,Brad Nelson,Eric Monnet,Zhijie Wang,Wenqiang Liu

doi:10.1002/ame2.12124

Michael Nguyen-Truong, June Boon + Show 5 more

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https://doi.org/10.1002/ame2.12124

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Abstract

BackgroundRight ventricle failure (RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients. Currently, the mechanisms of RVF are not fully understood and it is partly due to the lack of large animal models in adult RVF. In this study, we aim to establish a model of RVF in adult ovine and examine the structure and function relations in the RV.MethodsRV pressure overload was induced in adult male sheep by revised pulmonary artery constriction (PAC). Briefly, an adjustable hydraulic occluder was placed around the main pulmonary artery trunk. Then, repeated saline injection was performed at weeks 0, 1, and 4, where the amount of saline was determined in an animal‐specific manner. Healthy, age‐matched male sheep were used as additional controls. Echocardiography was performed bi‐weekly and on week 11 post‐PAC, hemodynamic and biological measurements were obtained.ResultsThis PAC methodology resulted in a marked increase in RV systolic pressure and decreases in stroke volume and tricuspid annular plane systolic excursion, indicating signs of RVF. Significant increases in RV chamber size, wall thickness, and Fulton's index were observed. Cardiomyocyte hypertrophy and collagen accumulation (particularly type III collagen) were evident, and these structural changes were correlated with RV dysfunction.ConclusionIn summary, the animal‐specific, repeated PAC provided a robust approach to induce adult RVF, and this ovine model will offer a useful tool to study the progression and treatment of adult RVF that is translatable to human diseases.

Highlights

Right ventricle failure (RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients.[1]
We found a significant correlation between type III collagen content and ejection time and a trend of moderate correlation between type III collagen content and stroke volume (Figure 4G,H)
As we found that both Fulton index and width of the cardiomyocyte were correlated with the RV systolic pressure (RVSP), we further investigated the relations between these two hypertrophy indices

Summary

Introduction

Right ventricle failure (RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients.[1]. Preclinical (animal) models are powerful tools to investigate various human diseases including RVF.[7] Compared to small animal models, large animal models better mimic human physiology and pathophysiology[10,11,12,13] and are advantageous in studying both the pathogenesis and potential therapeutics that are more translatable to human patients.[14] To date, various methods have been used to establish RV pressure overload, the most common etiology of RVF. Conclusion: In summary, the animal-specific, repeated PAC provided a robust approach to induce adult RVF, and this ovine model will offer a useful tool to study the progression and treatment of adult RVF that is translatable to human diseases

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