Dynamic deformation characteristics of porcine aortic valve leaflet under normal and hypertensive conditions

Abstract

Calcific aortic valve (AV) disease has a high prevalence in the United States, and hypertension is correlated to early onset of the disease. The cause of the disease is poorly understood, although biological and remodeling responses to mechanical forces, such as membrane tension, have been hypothesized to play a role. The mechanical behavior of the native AV has, therefore, been the focus of many recent studies. In the present study, the dynamic deformation characteristics of the AV leaflet and the effects of hypertension on leaflet deformation are quantified. Whole porcine aortic roots were trimmed and mounted in an in vitro pulsatile flow loop and subjected to normal (80/120 mmHg), hypertensive (120/160 mmHg), or severe hypertensive (150/190 mmHg) conditions. Local valve leaflet deformations were calculated with dual-camera photogrammetry method: by tracking the motion of markers placed on the AV leaflets in three dimensions and calculating their spatial deformations. The results demonstrate that, first, during diastole, high transvalvular pressure induces a stretch waveform which plateaus over the diastolic duration in both circumferential and radial directions. During systole, the leaflet stretches in the radial direction due to forward flow drag forces but compresses in the circumferential direction in a manner in agreement with Poisson's effect. Second, average diastolic and systolic stretch ratios were quantified in the radial and circumferential directions in the base and belly region of the leaflet, and diastolic stretch was found to increase with increasing pressure conditions. dynamic stretch; dynamic strain; hypertension; dual-camera photogrammetry CALCIFIC AORTIC VALVE (AV) disease has a high prevalence, especially among the elderly (16). In the Unites States alone, AV disease is the third most common cardiovascular pathology and is a strong risk factor for other cardiac-related deaths (17,18,21). Every year, nearly 95,000 procedures are performed on the AV, making AV surgeries second only to the coronary bypass procedure (13,27). The number of patients requiring AV surgery is expected to triple by 2050 (34). A calcified AV has increased thickness, collagen fiber disarray, and deposition of calcium, and thus has a drastically reduced leaflet flexibility, disabling native valve kinematics and function, resulting in AV stenosis and/or regurgitation and heart failure (19).The majority of AV calcification has an idiopathic etiology. Recent studies have shown that AV sclerosis is an active process akin to atherosclerosis, involving lipoprotein deposition, chronic inflammation, and active leaflet calcification mediated by cell differentiation (11). Furthermore, in a manner similar to the correlation between adverse hemodynamic/mechanical environment and atherosclerosis formation (9, 10), data in the literature suggest that adverse mechanical forces may elicit pathological responses of AV leaflets. Isolated mechanical forces, including stretch, pressure, and fluid shear, have been shown to affect the remod...

Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve

“…Mechanical stresses are oriented circumferentially in the healthy valve and are altered from increased hemodynamic pressures or aberrant deformations due to altered wall stresses during the contractile cycle during ischemic cardiomyopathy. These altered stresses typically manifest as altered strains (1,12,13,27). In an attempt to mimic this cell microenvironment in a simplified model, we engineered 2D lamellae of primary ovine VECs by seeding the cells on micropatterned (28) deformable elastomeric substrates.…”

“…VEC monolayers were subject to 0% (control), 10%, or 20% uniaxial cyclic strain at 1 Hz for 24 or 48 h using a custom-built cyclic stretcher device (Movies S1 and S2). The latter two strain magnitudes are representative of low-or high-strain regimes in mammalian cardiac valves (27,57). Cyclic strain was either applied parallel (termed "anisotropic") or orthogonal (termed "anisotropic-orthogonal") to initial tissue alignment, simulating healthy or diseased valves (12,13).…”

Total ellipse of the heart valve: the impact of eccentric stent distortion on the regional dynamic deformation of pericardial tissue leaflets of a transcatheter aortic valve replacement

“…A regular array of tissue dye markers with a 1 mm grid spacing was applied using tissue marking dye (Black Shandon Tissue Marking Dye, Thermoelectron Corporation, Pittsburgh, PA, USA) to the aortic surface of the leaflets using a template placed behind the leaflet as reference (figure 1a,b). Valves were deployed into two aortic annulus models: a circular control annulus (22 figure 1c,d ), representative of highly eccentric explanted and in vivo TAVRs from CT imaging [5,6]. Both circular and eccentric orifices were constructed such that the cross-sectional orifice areas were the same.…”

Hemodynamic and Cellular Response Feedback in Calcific Aortic Valve Disease

“…They also compared their valve explant experimental results with shear stresses calculated for in vivo measurements using their theoretical model and found that they were similar (ie, 77-92 dynes/cm 2 on the ventricular side). In addition, Yap et al 77 found that hypertension increases the stretch of the valve tissue in both the radial and circumferential directions. Severe hypertension caused an even higher degree of valve stretch.…”

“…96 However, when pathological blood flow exposes the endothelium to disturbed, low-shear-stress flow on the aortic side, endothelial dysfunction can occur, leading to inflammation, enhanced permeability of small molecules through the EC barrier, and potentially apoptosis of the ECs (Figure 3). 1,77,97,98 The increase in endothelial permeability results in nonspecific regulation of the diffusion of molecules into the tissue such as inflammatory cytokines 97 that may lead to propagation of the myofibroblast phenotype of VICs and disease progression. In addition, EC apoptosis would reduce expression and diffusion of protective paracrine signaling molecules (eg, NO and CNP), which results in less regulation of the activated myofibroblast phenotype.…”