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A Revised Pulmonary Artery Constriction Model of Right Ventricle Failure in Adult Ovine
Author(s) -
NguyenTruong Michael,
Liu Wenqiang,
Boon June,
Nelson Brad,
Easley Jeremiah,
Monnet Eric,
Wang Zhijie
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.532.14
Subject(s) - pressure overload , medicine , ventricle , pulmonary artery , hemodynamics , saline , cardiology , volume overload , constriction , heart failure , muscle hypertrophy , pulmonary hypertension , anesthesia , cardiac hypertrophy
Right ventricle failure (RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients [1]. Currently, the mechanisms of RVF are not fully understood and it is partly due to the lack of large animal models to investigate the pathogenesis that includes biomechanical properties and mechanobiology of the RV [2,3]. In this study, we aim to establish an adult ovine model of RVF to examine the hemodynamic, structural and mechanical adaptations of the RV under chronic pressure overload. Methods All procedures were approved by Colorado State University IACUC. To induce RV pressure overload, ~8‐month old male sheep underwent a revised method of pulmonary artery constriction (PAC) by patient‐specific, repeated filling of an adjustable hydraulic occluder (Norfolk Vet Products, IL) with saline at week 0, 1, and 4. The amount of saline injected was determined to acutely elevate the RV pressure to be comparable to its own left ventricle pressure. Healthy, age‐matched male sheep were used as controls (CTL). Echocardiography was performed in awake animals at baseline (week 0) and 2, 4, 6, 8, and 11 weeks post PAC. On week 11, animals were anesthetized and catheterized with Swan‐Ganz and pressure‐volume (PV) catheters to obtain hemodynamic measurements. Finally, hearts were extracted and tissue thickness and weight were measured. RV hypertrophy was quantified by RV wall thickness using a caliper and Fulton's index as the weight of RV/(LV+Septum). One‐way ANOVA with repeated measures and Dunnett's post hoc tests were performed to examine RV changes over time. Unpaired Student's t‐test was performed between the CTL and PAC groups. p<0.05 was considered statistically significant compared to baseline (week 0) or CTL. Results The new PAC methodology resulted in a marked increase in RV systolic pressure (RVSP) and decreases in stroke volume and tricuspid annular plane systolic excursion (TAPSE) at week 11 (Fig. a–c). During the PAC period, impaired ejection dynamics was observed by a gradual decrease of the ratio of acceleration time to ejection time (AT/ET) (Fig. d). Significant increases in Fulton's index and RV free wall thickness suggested RV hypertrophy under PAC (Fig. e–f). The systemic circulation and LV were not affected and functioned normally (data not shown). Conclusion The revised patient specific, repeated PAC method provided an easy and robust approach to induce RVF secondary to pressure overload. The development of RVF was evident by changes in RV structure and function as described above. The histological and mechanical changes will be further investigated. This ovine model will offer a useful tool to study the progression and treatment of RVF in large animal species. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .