Right Ventricular Fiber Structure as a Compensatory Mechanism in Pressure Overload: A Computational Study.

Right ventricular failure (RVF) is a lethal condition in diverse pathologies. Pressure overload is the most common etiology of RVF, but our understanding of the tissue structure remodeling and other biomechanical factors involved in RVF is limited. Some remodeling patterns are interpreted as compensatory mechanisms including myocyte hypertrophy, extracellular fibrosis, and changes in fiber orientation. However, the specific implications of these changes, especially in relation to clinically observable measurements, are difficult to investigate experimentally. In this computational study, we hypothesized that, with other variables constant, fiber orientation alteration provides a quantifiable and distinct compensatory mechanism during RV pressure overload (RVPO). Numerical models were constructed using a rabbit model of chronic pressure overload RVF based on intraventricular pressure measurements, CINE magnetic resonance imaging (MRI), and diffusion tensor MRI (DT-MRI). Biventricular simulations were conducted under normotensive and hypertensive boundary conditions using variations in RV wall thickness, tissue stiffness, and fiber orientation to investigate their effect on RV pump function. Our results show that a longitudinally aligned myocardial fiber orientation contributed to an increase in RV ejection fraction (RVEF). This effect was more pronounced in response to pressure overload. Likewise, models with longitudinally aligned fiber orientation required a lesser contractility for maintaining a target RVEF against elevated pressures. In addition to increased wall thickness and material stiffness (diastolic compensation), systolic mechanisms in the forms of myocardial fiber realignment and changes in contractility are likely involved in the overall compensatory responses to pressure overload.

Animal model of reversible, right ventricular failure.

BACKGROUND: Heart failure is a leading cause of death but very little is known about right ventricular (RV) failure (RVF) and right ventricular recovery (RVR). A robust animal model of reversible, RVF does not exist, which currently limits research opportunities and clinical progress. We sought to develop an animal model of reversible, pressure-overload RVF to study RVF and RVR. MATERIALS AND METHODS: Fifteen New Zealand rabbits underwent implantation of a fully implantable, adjustable, pulmonary artery band. Animals were assigned to the control, RVF, and RVR groups (n = 5 for each). For the RVF and RVR groups, the pulmonary artery bands were serially tightened to create RVF and released for RVR. Echocardiographic, cardiac magnetic resonance imaging, and histologic analysis were performed. RESULTS: RV chamber size and wall thickness increased during RVF and regressed during RVR. RV volumes were 1023 µL ± 123 for control, 2381 µL ± 637 for RVF, and 635 µL ± 549 for RVR, and RV wall thicknesses were 0.98 mm ± 0.12 for controls (P = 0.05), 1.72 mm ± 0.60 for RVF, and 1.16 mm ± 0.03 for RVR animals (P = 0.04), respectively. Similarly, heart weight, liver weight, cardiomyocyte size, and the degree of cardiac and hepatic fibrosis increased with RVF and decreased during RVR. CONCLUSIONS: We report an animal model of chronic, reversible, pressure-overload RVF to study RVF and RVR. This model will be used for preclinical studies that improve our understanding of the mechanisms of RVF and that develop and test RV protective and RVR strategies to be studied later in humans.

Characterization of regional deformation and material properties of the intact explanted vein by microCT and computational analysis.

PURPOSE: Detailed mechanical information of the vein is important to better understand remodeling of the vessel in disease states, but has been difficult to obtain due to its thinness, unique geometry, and limitations of mechanical testing. This study presents a novel method for characterizing deformation of the intact explanted vein under physiological loads and determining its material properties by combining high-resolution imaging and computational analysis. METHODS: High-resolution CT (microCT) was used to image an iodine-stained, excised porcine internal jugular vein sample under extension to 100% and 120% of in situ length, and inflation and 2, 10, 20 mmHg of pressure, inside a microCT-compatible hydrostatic loading chamber. Regional strains were measured with the finite element (FE) image registration method known as Hyperelastic Warping. Material properties were approximated with inverse FE characterization by optimizing stiffness-related coefficients so to match simulated strains to the experimental measurements. RESULTS: The observed morphology and regional strain of the vein were found to be relatively heterogeneous. The regional variability in the measured strain was primarily driven by geometry. Although iodine treatment may result in tissue stiffening, which requires additional investigation, it is effective in allowing detailed detection of vein geometry. CONCLUSIONS: The feasibility and utility of using microCT and computational analysis to characterize mechanical responses and material properties of the vein were demonstrated. The presented method is a promising alternative or addition to mechanical testing for characterizing veins or other similarly delicate vessels in their native anatomical configuration under a wide range of realistic or simulated environmental and loading conditions.