John C. Criscione

Importance of Mitral Valve Second-Order Chordae for Left Ventricular Geometry, Wall Thickening Mechanics, and Global Systolic Function

Background—Mitral valvular–ventricular continuity is important for left ventricular (LV) systolic function, but the specific contributions of the anterior leaflet second-order “strut” chordae are unknown. Methods and Results—Eight sheep had radiopaque markers implanted to silhouette the LV, annulus, and papillary muscles (PMs); 3 transmural bead columns were inserted into the mid-lateral wall between the PMs. The strut chordae were encircled with exteriorized wire snares. Three-dimensional marker images and hemodynamic data were acquired before and after chordal cutting. Preload recruitable stroke work (PRSW) and end-systolic elastance (Ees) were calculated to assess global LV systolic function (n=7). Transmural strains were measured from bead displacements (n=4). Chordal cutting caused global LV dysfunction: Ees (1.48±1.12 versus 0.98±1.30 mm Hg/mL, P=0.04) and PRSW (69±16 versus 60±15 mm Hg, P=0.03) decreased. Although heart rate and time from ED to ES were unchanged, time of mid-ejection was delayed (125±18 versus 136±19 ms, P=0.01). Globally, the LV apex and posterior PM tip were displaced away from the fibrous annulus and LV base-apex length increased at end-diastole and end-systole (all +1 mm, P<0.05). Locally, subendocardial end-diastolic strains occurred: Longitudinal strain (E22) 0.030±0.013 and radial thickening (E33) 0.081±0.041 (both P<0.05 versus zero). Subendocardial systolic shear strains were also perturbed: Circumferential-longitudinal “micro-torsion” (E12) (0.099±0.035 versus 0.075±0.025) and circumferential radial shear (E13) (0.084±0.023 versus 0.039±0.008, both P<0.05). Conclusion—Cutting second-order chords altered LV geometry, remodeled the myocardium between the PMs, perturbed local systolic strain patterns affecting micro-torsion and wall-thickening, and caused global systolic dysfunction, demonstrating the importance of these chordae for LV structure and function.

Stented artery biomechanics and device design optimization.

The deployment of a vascular stent aims to increase lumen diameter for the restoration of blood flow, but the accompanied alterations in the mechanical environment possibly affect the long-term patency of these devices. The primary aim of this investigation was to develop an algorithm to optimize stent design, allowing for consideration of competing solid mechanical concerns (wall stress, lumen gain, and cyclic deflection). Finite element modeling (FEM) was used to estimate artery wall stress and systolic/diastolic geometries, from which single parameter outputs were derived expressing stress, lumen gain, and cyclic artery wall deflection. An optimization scheme was developed using Lagrangian interpolation elements that sought to minimize the sum of these outputs, with weighting coefficients. Varying the weighting coefficients results in stent designs that prioritize one output over another. The accuracy of the algorithm was confirmed by evaluating the resulting outputs of the optimized geometries using FEM. The capacity of the optimization algorithm to identify optimal geometries and their resulting mechanical measures was retained over a wide range of weighting coefficients. The variety of stent designs identified provides general guidelines that have potential clinical use (i.e., lesion-specific stenting).

Rivlin’s Representation Formula is Ill-Conceived for the Determination of Response Functions via Biaxial Testing

The experimental determination of a strain energy function W for a rubber specimen must address departures from an elastic ideal in a rational fashion. Herein, such a rational experimental method is developed for biaxial stretching experiments and applied to rubber data in the literature. It is shown that Rivlin’s representation formula is experimentally ill-conceived because experimental error is magnified to the extent that error obscures trends in the response function plots. Upon developing direct tensor expressions for the response function calculations, we show that Rivlin’s representation formula (or any such constitutive law that has high covariance amongst the response terms) magnifies experimental error greatly. By “high covariance”, we mean the inner product amongst the response terms in the constitutive law is nearly equal to the maximum possible value — i.e., the product of their magnitudes. Moreover, we show that the second partials of W with respect to I1 and I2 should approach infinity as the strain decreases. Using an alternate set of invariants with minimal covariance (i.e., a null inner product amongst the response terms), a W for rubber can be determined forthwith.

Constitutive framework optimized for myocardium and other high-strain, laminar materials with one fiber family

Abstract Central to this analysis is the identification of six rotation invariant scalars α 1–6 that succinctly define the strain in materials that have one family of parallel fibers arranged in laminae. These scalars were chosen so as to minimize covariance amongst the response terms in the hyperelastic limit, and they are termed strain attributes because it is necessary to distinguish them from strain invariants. The Cauchy stress t is expressed as the sum of six response terms, almost all of which are mutually orthogonal for finite strain (i.e. 14 of the 15 inner products vanish). For small deformations, the response terms are entirely orthogonal (i.e. all 15 inner products vanish). A response term is the product of a response function with its associated kinematic tensor. Each response function is a scalar partial derivative of the strain energy W with respect to a strain attribute. Applications for this theory presently include myocardium (heart muscle) which is often modeled as having muscle fibers arranged in sheets. Utility for experimental identification of strain energy functions is demonstrated by showing that common tests on incompressible materials can directly determine terms in W . Since the described set of strain attributes reduces the covariance amongst response terms, this approach may enhance the speed and precision of inverse finite element methods.

Assessment of Minimally Invasive Device That Provides Simultaneous Adjustable Cardiac Support and Active Synchronous Assist in an Acute Heart Failure Model

One of the major maladaptive changes after a major heart attack or cardiac event is an initial decline in pumping capacity of the heart leading to activation of a variety of compensatory mechanisms, and subsequently a phenomenon known as cardiac or left ventricular remodeling, i.e., a geometrical change in the architecture of the left ventricle. Evidence suggests that the local mechanical environment governs remodeling processes. Thus, in order to control two important mechanical parameters, cardiac size and cardiac output, we have developed a minimally invasive direct cardiac contact device capable of providing two actions simultaneously: (1) adjustable cardiac support to modulate cardiac size and (2) synchronous active assist to modulate cardiac output. As a means of enabling experiments to determine the role of these mechanical parameters in reverse remodeling or ventricular recovery, the device was further designed to (1) be deployed via minimally invasive surgical procedures, (2) allow uninhibited motion of the heart, (3) remain in place about the heart via an intrinsic pneumatic attachment, and (4) provide direct cardiac compression without aberrantly inverting the curvature of the heart. These actions and features are mapped to particular design solutions and assessed in an acute implantation in an ovine model of acute heart failure (esmolol overdose). The passive support component was used to effectively shift the EDPVR leftward, i.e., counter to the effects of disease. The active assist component was used to effectively decompress the constrained heart and restore lost cardiac output and stroke work in the esmolol failure model. It is expected that such a device will provide better control of the mechanical environment and thereby provide cardiac surgeons a broader range of therapeutic options and unique intervention possibilities.

Development of a Non-Blood Contacting Cardiac Assist and Support Device: An In Vivo Proof of Concept Study

One of the maladaptive changes following a heart attack is an initial decline in pumping capacity, which leads to activation of compensatory mechanisms, and subsequently, a phenomenon known as cardiac or left ventricular remodeling. Evidence suggests that mechanical cues are critical in the progression of congestive heart failure. In order to mediate two important mechanical parameters, cardiac size and cardiac output, we have developed a direct cardiac contact device capable of two actions: (1) adjustable cardiac support to modulate cardiac size and (2) synchronous active assist to modulate cardiac output. In addition, the device was designed to (1) remain in place about the heart without tethering, (2) allow free normal motion of the heart, and (3) provide assist via direct cardiac compression without abnormally inverting the curvature of the heart. The actions and features described above were mapped to particular design solutions and assessed in an acute implantation in an ovine model of acute heart failure (esmolol overdose). A balloon catheter was inflated in the vena cava to reduce preload and determine the end-diastolic pressure-volume relationship with and without passive support. A Millar PV Loop catheter was inserted in the left ventricle to acquire pressure-volume data throughout the experiments. Fluoroscopic imaging was used to investigate effects on cardiac motion. Implementation of the adjustable passive support function of the device successfully modulated the end-diastolic pressure-volume relationship toward normal. The active assist function successfully restored cardiac output and stroke work to healthy baseline levels in the esmolol induced failure model. The device remained in place throughout the experiment and when de-activated, did not inhibit cardiac motion. In this in vivo proof of concept study, we have demonstrated that a single device can be used to provide both passive constraint/support and active assist. Such a device may allow for controlled, disease specific, flexible intervention. Ultimately, it is hypothesized that the combination of support and assist could be used to facilitate cardiac rehabilitation therapy. The principles guiding this approach involve simply creating the conditions under which natural growth and remodeling processes are guided in a therapeutic manner. For example, the passive support function could be incrementally adjusted to gradually reduce the size of the dilated myocardium, while the active assist function can be implemented as necessary to maintain cardiac output and decompress the heart.

Characterization of mechanical behavior of a porcine pulmonary artery strip using a randomized uniaxial stretch and stretch-rate protocol

BackgroundMuch of the experimental work in soft tissue mechanics has been focused on fitting approximate relations for specific tissue types from aggregate data on multiple samples of the tissue. Such relations are needed for modeling applications and have reasonable predictability – especially given the natural variance in specimens. There is, however, much theoretical and experimental work to be done in determining constitutive behaviors for particular specimens and tissues. In so doing, it may be possible to exploit the natural variation in tissue ultrastructure – so to relate ultrastructure composition to tissue behavior. Thus, this study focuses on an experimental method for determining constitutive behaviors and illustrates the method with analysis of a porcine pulmonary artery strip. The method characterizes the elastic part of the response (implicitly in terms of stretch) and the inelastic part in terms of short term stretch history (i.e., stretch-rate) Ht 2, longer term stretch history Ht 1, and time since the start of testing T.MethodsA uniaxial testing protocol with a random stretch and random stretch-rate was developed. The average stress at a particular stretch was chosen as the hyperelastic stress response, and deviation from the mean at this particular stretch is chosen as the inelastic deviation. Multivariable Linear Regression Analysis (MLRA) was utilized to verify if Ht 2, Ht 1, and T are important factors for characterizing the inelastic deviation. For acquiring Ht 2and Ht 1, an integral function type of stretch history was employed with time constants chosen from the relaxation spectrum of an identical size strip from the same tissue with the same orientation. Finally, statistical models that characterize the inelasticity were developed at various, nominal values of stretch, and their predictive capability was examined.ResultsInelastic deviation from hyperelasticity was high (31%) for low stretch and declined significantly with increasing stretch to a nadir of 3.6% for a stretch of 1.7. The inelastic deviation then increased with increasing stretch at the same point in the stress-strain curve where stiffness began to increase strikingly. MLRA showed that T is a major inelastic parameter at low deformation. For moderate and high deformations, Ht 2and Ht 1were dominant.DiscussionA randomized uniaxial testing protocol was applied to a strip of porcine pulmonary artery to characterize the elasticity and inelasticity of a soft tissue. We were successful in determining the elastic response and the factors that gave rise to the inelastic deviation. This investigation seeks methods to better define, phenomenologically, the elastic and inelastic behavior of soft tissues.

Functional adaptation of bovine mesenteric lymphatic vessels to mesenteric venous hypertension

Lymph flow is the primary mechanism for returning interstitial fluid to the blood circulation. Currently, the adaptive response of lymphatic vessels to mesenteric venous hypertension is not known. This study sought to determine the functional responses of postnodal mesenteric lymphatic vessels. We surgically occluded bovine mesenteric veins to create mesenteric venous hypertension to elevate mesenteric lymph flow. Three days after surgery, postnodal mesenteric lymphatic vessels from mesenteric venous hypertension (MVH; n = 7) and sham surgery (Sham; n = 6) group animals were evaluated and compared. Contraction frequency (MVH: 2.98 ± 0.75 min(-1); Sham: 5.42 ± 0.81 min(-1)) and fractional pump flow (MVH: 1.14 ± 0.30 min(-1); Sham: 2.39 ± 0.32 min(-1)) were significantly lower in the venous occlusion group. These results indicate that postnodal mesenteric lymphatic vessels adapt to mesenteric venous hypertension by reducing intrinsic contractile activity.

Changes in the interfacial shear resistance of disc annulus fibrosus from genipin crosslinking

Crosslinking soft tissue has become more common in tissue engineering applications, and recent studies have demonstrated that soft tissue mechanical behavior can be directly altered through crosslinking. Using a recently reported test method that shears adjacent disc lamella, the effect of genipin crosslinking on interlamellar shear resistance was studied using in vitro bovine disc annulus. Specimens of adjacent lamella were dissected from four discs taken from three fresh frozen bovine tails. These specimens were paired and soaked in either 50 mM EPPS Phosphate (ph9) with 20 mM genipin at 37 °C for 4 h or in 50 mM EPPS Phosphate (ph9) of which twelve specimens (6 per treatment) were successfully tested and analyzed. Crosslinked specimens were noted to have significantly higher yield force per width (59%), peak force per width (70%), and resilience (69%) compared to sham treated controls, supporting the hypothesis that genipin crosslinking increases the resistance to interlamellar shear of the annulus interface. Additionally, a possible dependency may exist between the interlamellar shear strength and neighboring lamella because of the bridging fiber network previously described by other investigators.

Modulation of Diastolic Filling Using an Epicardial Diastolic Recoil Device

Diastolic dysfunction likely contributes to all cases of congestive heart failure and is solely responsible for many. Existing cardiac support devices largely ignore diastolic dysfunction and may exacerbate it. Current diastolic devices in development rely on either extensive extraventricular fixation or intraventricular implantation with complications associated with blood contact. A diastolic recoil device is proposed that pneumatically locks to the outside of the heart wall. The end-diastolic total biventricular pressure-volume relationship (EDTBPVR) was used to evaluate, in vitro, the ability of a recoil device to modulate filling mechanics through pneumatic locking as the method of fixation. The pressure in a model heart was incremented and the corresponding volume changes were measured. The heart model and device were pneumatically locked together using a vacuum sac to model the pericardium. The diastolic recoil component shifted the EDTBPVR towards lower pressures at low volumes, providing up to 0.9 kPa (9 cm H2O) of suction, demonstrating enhanced diastolic recoil at beginning diastole. We conclude that pneumatic locking appears to be a viable method for a recoil device to engage the heart.