Functional and pathological characteristics of reversible remodeling in a canine right ventricle in response to volume overloading and volume unloading

PURPOSES: Patients who undergo right ventricular (RV) outflow augmentation inevitably develop RV remodeling due to pulmonary insufficiency-related volume overload (VOL). However, the reversibility of this remodeling is not fully understood. The goal of this study was to establish an animal model of VOL and unloading to characterize the functional and pathological characteristics and reversibility of RV remodeling. METHODS: VOL-RV was successfully induced by establishing direct RV-pulmonary artery (PA) bypass for 12 weeks in beagle canines. There were no procedure-related mortalities (n = 8). RESULTS: The RV developed typical functional features of VOL-related remodeling, such as a significant increase in end-diastolic/systolic volume and end-systolic pressure and a significant reduction in ejection fraction at 12 weeks, as assessed by three-dimensional echocardiography and cardiac catheterization. The RV developed typical pathological signs of remodeling, microstructural disorganization of cardiomyocytes, and/or structural/functional deterioration of the mitochondria. Volume unloading by division of the RV-PA bypass reversed the increase in the end-systolic/diastolic volume over 4 weeks when compared with a sham operation (n = 4 each). In addition, the bypass division also reversed the pathological changes seen in VOL-RV. CONCLUSIONS: VOL-RV that yielded typical functional and pathological features of RV remodeling was reproducibly achieved by direct RV-PA bypass in canines. The RV remodeling due to VOL was functionally and pathologically reversed by volume unloading via the bypass division.