In vitro hemodynamic evaluation of ventricular suction conditions of the EVAHEART ventricular assist pump.

PURPOSE: Mismatches between pump output and venous return in a continuous-flow ventricular assist device may elicit episodes of ventricular suction. This research describes a series of in vitro experiments to characterize the operating conditions under which the EVAHEART centrifugal blood pump (Sun Medical Technology Research Corp., Nagano, Japan) can be operated with minimal concern regarding left ventricular (LV) suction. METHODS: The pump was interposed into a pneumatically driven pulsatile mock circulatory system (MCS) in the ventricular apex to aorta configuration. Under varying conditions of preload, afterload, and systolic pressure, the speed of the pump was increased step-wise until suction was observed. Identification of suction was based on pump inlet pressure. RESULTS: In the case of reduced LV systolic pressure, reduced preload (=10 mmHg), and afterload (=60 mmHg), suction was observed for speeds=2,200 rpm. However, suction did not occur at any speed (up to a maximum speed of 2,400 rpm) when preload was kept within 10-14 mmHg and afterload=80 mmHg. Although in vitro experiments cannot replace in vivo models, the results indicated that ventricular suction can be avoided if sufficient preload and afterload are maintained. CONCLUSION: Conditions of hypovolemia and/or hypotension may increase the risk of suction at the highest speeds, irrespective of the native ventricular systolic pressure. However, in vitro guidelines are not directly transferrable to the clinical situation; therefore, patient-specific evaluation is recommended, which can be aided by ultrasonography at various points in the course of support.

The relation between collagen fibril kinematics and mechanical properties in the mitral valve anterior leaflet.

We have recently demonstrated that the mitral valve anterior leaflet (MVAL) exhibited minimal hysteresis, no strain rate sensitivity, stress relaxation but not creep (Grashow et al., 2006, Ann Biomed Eng., 34(2), pp. 315-325; Grashow et al., 2006, Ann Biomed. Eng., 34(10), pp. 1509-1518). However, the underlying structural basis for this unique quasi-elastic mechanical behavior is presently unknown. As collagen is the major structural component of the MVAL, we investigated the relation between collagen fibril kinematics (rotation and stretch) and tissue-level mechanical properties in the MVAL under biaxial loading using small angle X-ray scattering. A novel device was developed and utilized to perform simultaneous measurements of tissue level forces and strain under a planar biaxial loading state. Collagen fibril D-period strain (epsilonD) and the fibrillar angular distribution were measured under equibiaxial tension, creep, and stress relaxation to a peak tension of 90 N/m. Results indicated that, under equibiaxial tension, collagen fibril straining did not initiate until the end of the nonlinear region of the tissue-level stress-strain curve. At higher tissue tension levels, epsilonD increased linearly with increasing tension. Changes in the angular distribution of the collagen fibrils mainly occurred in the tissue toe region. Using epsilonD, the tangent modulus of collagen fibrils was estimated to be 95.5+/-25.5 MPa, which was approximately 27 times higher than the tissue tensile tangent modulus of 3.58+/-1.83 MPa. In creep tests performed at 90 N/m equibiaxial tension for 60 min, both tissue strain and epsilonD remained constant with no observable changes over the test length. In contrast, in stress relaxation tests performed for 90 min epsilonD was found to rapidly decrease in the first 10 min followed by a slower decay rate for the remainder of the test. Using a single exponential model, the time constant for the reduction in collagen fibril strain was 8.3 min, which was smaller than the tissue-level stress relaxation time constants of 22.0 and 16.9 min in the circumferential and radial directions, respectively. Moreover, there was no change in the fibril angular distribution under both creep and stress relaxation over the test period. Our results suggest that (1) the MVAL collagen fibrils do not exhibit intrinsic viscoelastic behavior, (2) tissue relaxation results from the removal of stress from the fibrils, possibly by a slipping mechanism modulated by noncollagenous components (e.g. proteoglycans), and (3) the lack of creep but the occurrence of stress relaxation suggests a "load-locking" behavior under maintained loading conditions. These unique mechanical characteristics are likely necessary for normal valvular function.

Fiber kinematics of small intestinal submucosa under biaxial and uniaxial stretch.

Improving our understanding of the design requirements of biologically derived collagenous scaffolds is necessary for their effective use in tissue reconstruction. In the present study, the collagen fiber kinematics of small intestinal submucosa (SIS) was quantified using small angle light scattering (SALS) while the specimen was subjected to prescribed uniaxial or biaxial strain paths. A modified biaxial stretching device based on Billiar and Sacks (J. Biomech., 30, pp. 753-7, 1997) was used, with a real-time analysis of the fiber kinematics made possible due to the natural translucency of SIS. Results indicated that the angular distribution of collagen fibers in specimens subjected to 10% equibiaxial strain was not significantly different from the initial unloaded condition, regardless of the loading path (p=0.31). Both 10% strip biaxial stretch and uniaxial stretches of greater than 5% in the preferred fiber direction led to an increase in the collagen fiber alignment along the same direction, while 10% strip biaxial stretch in the cross preferred fiber direction led to a broadening of the distribution. While an affine deformation model accurately predicted the experimental findings for a biaxial strain state, uniaxial stretch paths were not accurately predicted. Nonaffine structural models will be necessary to fully predict the fiber kinematics under large uniaxial strains in SIS.

Planar biaxial creep and stress relaxation of the mitral valve anterior leaflet.

A fundamental assumption in mitral valve (MV) therapies is that a repaired or replaced valve should mimic the functionality of the native valve as closely as possible. Thus, improvements in valvular treatments are dependent on the establishment of a complete understanding of the function and mechanical properties of the native normal MV. In a recent study [Grashow et al. ABME 34(2), 2006] we demonstrated that the planar biaxial stress-strain relationship of the MV anterior leaflet (MVAL) exhibited minimal hysteresis and a stress-strain response independent of strain rate, suggesting that MVAL could be modeled as a "quasi-elastic" material. The objective of our current study was to expand these results to provide a more complete picture of the time-dependent mechanical properties of the MVAL. To accomplish this, biaxial stress-relaxation and creep studies were performed on porcine MVAL specimens. Our primary finding was that while the MVAL leaflet exhibited significant stress relaxation, it exhibited negligible creep over the 3-h test. These results furthered our assertion that the MVAL functionally behaves not as a linear or non-linear viscoelastic material, but as an anisotropic quasi-elastic material. These results appear to be unique in the soft tissue literature; suggesting that valvular tissues are unequalled in their ability to withstand significant loading without time-dependent material effects. Moreover, insight into these specialized characteristics can help guide and inform efforts directed toward surgical repair and engineered valvular tissue replacements.

Biaixal stress-stretch behavior of the mitral valve anterior leaflet at physiologic strain rates.

Characterization of the mechanical properties of the native mitral valve leaflets at physiological strain rates is a critical step in improving our understanding of MV function and providing experimental data for dynamic constitutive models. We explored, for the first time, the effects of strain rate (from quasi-static to physiologic) on the biaxial mechanical properties of the native mitral valve anterior leaflet (MVAL). A novel high-speed biaxial testing device was developed, capable of achieving in vitro strain rates reported for the MVAL (Sacks et al., Ann. Biomed. Eng. 30(10):1280-1290, 2002). Porcine MVAL specimens were loaded to physiological load levels with cycle periods of 15, 1, 0.5, 0.1, and 0.05 s. The resulting loading stress-strain responses were found to be remarkably independent of strain rate. The hysteresis, defined as the fraction of the membrane strain energy between the loading and unloading curves tension-areal stretch curves, was low (approximately 12%) and did not vary with strain rate. The results of the present work indicated that MVAL tissues exhibit complete strain rate insensitivity at and below physiological strain rates under physiological loading conditions. These novel results suggest that experimental tests utilizing quasi-static strain rates are appropriate for constitutive model development for mitral valve tissues. The mechanisms underlying this quasi-elastic behavior are as yet unknown, but are likely an important functional aspect of native mitral valve tissues and clearly warrant further study.

Quantification of bladder smooth muscle orientation in normal and spinal cord injured rats.

Spinal cord injuries (SCI) often lead to severe bladder dysfunctions. Our previous studies have demonstrated that following SCI, rat bladder wall tissue became hypertrophied, significantly more compliant, and changed its mechanical behavior from orthotropic to isotropic. In order to elucidate the link between the tissue microstructure and mechanical properties of the wall, we have developed a novel semi-automated image analysis method to quantify smooth muscle bundle orientation and mass fraction in the bladder wall tissues from normal and 10 day-post-SCI rats. Results of the present study revealed that there were significant (p < 0.05) increases in smooth muscle area fractions as well as significantly (p < 0.001) fewer cell nuclei per muscle area in the SCI groups compared to the normal groups. Furthermore, while the normal rat bladders exhibited predominant smooth muscle orientation only in the longitudinal direction, the SCI rat bladders exhibited smooth muscles oriented in both the circumferential and longitudinal directions. These results provide first evidence that bladder smooth muscle cells exhibit hypertrophy rather than hyperplasia and developed a second, orthogonal orientation of smooth muscle bundles following SCI. The results of the present study corroborate our previous mechanical anisotropy data and provide the basis for development of structure-based constitutive models for urinary bladder wall tissue.

In vitro dynamic strain behavior of the mitral valve posterior leaflet.

Knowledge of mitral valve (MV) mechanics is essential for the understanding of normal MV function, and the design and evaluation of new surgical repair procedures. In the present study, we extended our investigation of MV dynamic strain behavior to quantify the dynamic strain on the central region of the posterior leaflet. Native porcine MVs were mounted in an in-vitro physiologic flow loop. The papillary muscle (PM) positions were set to the normal, taut, and slack states to simulate physiological and pathological PM positions. Leaflet deformation was measured by tracking the displacements of 16 small markers placed in the central region of the posterior leaflet. Local leaflet tissue strain and strain rates were calculated from the measured displacements under dynamic loading conditions. A total of 18 mitral valves were studied. Our findings indicated the following: (1) There was a rapid rise in posterior leaflet strain during valve closure followed by a plateau where no additional strain (i.e., no creep) occurred. (2) The strain field was highly anisotropic with larger stretches and stretch rates in the radial direction. There were negligible stretches, or even compression (stretch < 1) in the circumferential direction at the beginning of valve closure. (3) The areal strain curves were similar to the stretches in the trends. The posterior leaflet showed no significant differences in either peak stretches or stretch rates during valve closure between the normal, taut, and slack PM positions. (4) As compared with the anterior leaflet, the posterior leaflet demonstrated overall lower stretch rates in the normal PM position. However, the slack and taut PM positions did not demonstrate the significant difference in the stretch rates and areal strain rates between the posterior leaflet and the anterior leaflet. The MV posterior leaflet exhibited pronounced mechanically anisotropic behavior Loading rates of the MV posterior leaflet were very high. The PM positions influenced neither peak stretch nor stretch rates in the central area of the posterior leaflet. The stretch rates and areal strain rates were significantly lower in the posterior leaflet than those measured in the anterior leaflet in the normal PM position. However, the slack and taut PM positions did not demonstrate the significant differences between the posterior leaflet and the anterior leaflet. We conclude that PM positions may influence the posterior strain in a different way as compared to the anterior leaflet.

Molecular orientation of collagen in intact planar connective tissues under biaxial stretch.

Understanding of the mechanical behavior of collagenous tissues at different size scales is necessary to understand their physiological function as well as to guide their use as heterograft biomaterials. We conducted a first investigation of the kinematics of collagen at the molecular and fiber levels under biaxial stretch in an intact planar collagenous tissue. A synchrotron small angle X-ray scattering (SAXS) technique combined with a custom biaxial stretching apparatus was used. Collagen fiber behavior under biaxial stretch was then studied with the same specimens using small angle light scattering (SALS) under identical biaxial stretch states. Both native and glutaraldehyde modified bovine pericardium were investigated to explore the effects of chemical modification to collagen. Results indicated that collagen fiber and molecular orientation did not change under equibiaxial strain, but were observed to profoundly change under uniaxial stretch. Interestingly, collagen molecular strain initiated only after approximately 15% global tissue strain, potentially due to fiber-level reorganization occurring prior to collagen molecule loading. Glutaraldehyde treatment also did not affect collagen molecular strain behavior, indicating that chemical fixation does not alter intrinsic collagen molecular stiffness. No detectable changes in the angular distribution and D-period strain were found after 80 min of stress relaxation. It can be speculated that other mechanisms may be responsible for the reduction in stress with time under biaxial stretch. The results of this first study suggest that collagen fiber/molecular kinematics under biaxial stretch are more complex than under uniaxial deformation, and warrant future studies.