Preclinical Proof-of-Concept of a Minimally Invasive Direct Cardiac Compression Device for Pediatric Heart Support.

PURPOSE: For pediatric patients, extracorporeal membrane oxygenation (ECMO) remains the predominant mechanical circulatory support (MCS) modality for heart failure (HF) although survival to discharge rates remain between 50 and 60% for these patients. The device-blood interface and disruption of physiologic hemodynamics are significant contributors to poor outcomes. METHODS: In this study, we evaluate the preclinical feasibility of a minimally invasive, non-blood-contacting pediatric DCC prototype for temporary MCS. Proof-of-concept is demonstrated in vivo in an animal model of HF. Hemodynamic pressures and flows were examined. RESULTS: Minimally invasive deployment on the beating heart was successful without cardiopulmonary bypass or anticoagulation. During HF, device operation resulted in an immediate 43% increase in cardiac output while maintaining pulsatile hemodynamics. Compared to the pre-HF baseline, the device recovered up to 95% of ventricular stroke volume. At the conclusion of the study, the device was easily removed from the beating heart. CONCLUSIONS: This preclinical proof-of-concept study demonstrated the feasibility of a DCC device on a pediatric scale that is minimally invasive and non-blood contacting, with promising hemodynamic support and durability for the initial intended duration of use. The ability of DCC to maintain pulsatile MCS without blood contact represents an opportunity to mitigate the mortality and morbidity observed in non-pulsatile, blood-contacting MCS.

A New Strain Energy Function Representing the Passive Behavior of the Myocardium.

Classical models for the passive myocardium, such as the Fung and Holzapfel-Ogden models, are known to have high degeneracy as well as numerous mechanical and mathematical limitations, preventing their utility in microstructural experiments and precision medicine. Hence, the upper triangular (QR) decomposition and orthogonal strain attributes were leveraged to develop a new model using published biaxial data on slabs of left myocardium, resulting in a separable strain energy function. This new model, the Criscione-Hussein model, was compared with both the Fung and Holzapfel-Ogden models by quantifying the uncertainty, computational efficiency, and material parameter fidelity for all three models. As a result, the Criscione-Hussein model was found to significantly reduce the uncertainty and computational time (p < 0.05) and enhance the fidelity of the material parameters. Hence, the Criscione-Hussein model enhances the predictability for the passive behavior of the myocardium and may serve a role in creating more accurate computational models that provide better visualizations for the mechanical behavior of the heart and enable the experimental connection between the model and the myocardial microstructure.

Mechanical Cardiac Support With an Implantable Direct Cardiac Compression Device: Proof of Concept.

PURPOSE: We examined the hemodynamic effects of a new, implantable, direct cardiac assist device in an ovine heart failure model. DESCRIPTION: The device, which encompasses both left and right ventricles, is inserted through the pericardial apex and self-expands to encompass the heart without suturing. The intact pericardium anchors the device in place. The device has 2 concentric chamber layers: an internal chamber layer filled with fluid to conform to the heart and an external chamber layer filled with air that provides external compression and negative pressure to aid relaxation. EVALUATION: The device was implanted in 7 sheep with heart failure induced by microsphere embolization. Cardiac performance was assessed for 6 to 8 hours. The cardiac assist device provided cardiac systolic and diastolic assistance, as shown by pressure tracings of the left ventricle and aorta, pulmonary artery flow, and +dP/dt. Central venous pressure decreased during cardiac assistance. No anatomic damage was noted postmortem. CONCLUSIONS: Systolic and diastolic cardiac assistance can be achieved with this device that compresses and relaxes in synchrony with the native cardiac cycle.

Electrical weapons and rhabdomyolysis.

It has been suggested that an application of a conducted electrical weapon (CEW) might cause muscle injury such as rhabdomyolysis and an acute inflammatory response. We explored this hypothesis by testing the effects of electrical weapons on circulating markers of inflammation and muscle damage. In a prospective study, 29 volunteers received a full-trunk 5-s TASER® X26(E) CEW exposure. Venous blood samples were taken before, 5 min after, and at 24 h following the discharge. We tested for changes in serum levels of C-reactive protein (CRP), alkaline phosphatase (ALP), myoglobin, albumin, globulin, albumin/globulin ratio, aspartate and alanine aminotransferase, creatine kinase, total protein, bilirubin, and lactic acid dehydrogenase. Uncorrected CRP and myoglobin levels were lower in the immediate post exposure period (CRP levels 1.44 ± 1.39 v 1.43 ± 1.32 mg/L; p = 0.046 and myoglobin 36.8 ± 11.9 v 36.1 ± 13.9 µg/L; p = 0.0019) but these changes were not significant after correction for multiple comparisons. There were no changes in other biomarkers. At 24 h, CRP levels had decreased by 30% to 1.01 ± 0.80 mg/L (p = 0.001 from baseline). ALP was unchanged immediately after the CEW application but was reduced by 5% from baseline (66.2 ± 16.1 to 62.7 ± 16.1 IU/L; p = 0.0003) at 24 h. No other biomarkers were different from baseline at 24 h. A full-trunk electrical weapon exposure did not lead to clinically significant changes in the acute phase protein levels or changes in measures of muscle cellular injury. We found no biomarker evidence of rhabdomyolysis.

Electrical weapons, hematocytes, and ischemic cardiovascular accidents.

BACKGROUND: There have been case reports following the use of a conducted electrical weapon (CEW) suggesting that these devices might affect coagulation or thrombosis in at-risk individuals. The aim of this manuscript therefore is firstly to explore this hypothesis by reviewing each of these cases and secondly to report the results of a prospective study exploring a priori the effects of electrical weapons on hematocytes in a group of human volunteers. METHODS: First, we systematically reviewed all cases of adverse outcomes following CEW discharge that could be due to an effect on coagulation or thrombosis, with particular focus on the clinical scenario and its relationship with the weapon discharge. Second, we assessed hematocyte levels in venous blood from 29 volunteers before, 5 min after, and 24 h after receiving a full-trunk 5-s TASER® X26(E) CEW exposure. RESULTS: Following extensive review of the literature, we found 3 relevant case reports of possible vascular thromboembolic clinical events after CEW exposure, specifically a case of ischemic stroke, and 2 cases of ST-segment elevation myocardial infarctions. Review of these published cases failed to establish a plausible linkage to the CEW beyond a temporal association with significant emotional and physiological stress from a violent struggle. Our prospective study of biomarker change following CEW discharge revealed acutely increased values for WBC (white blood cells), specifically lymphocytes and monocytes, and a raised platelet count. Neutrophil levels decreased as a percentage of WBC. While these changes were statistically significant at 5 min, all results remained within established reference ranges. At 24 h, all values had returned to baseline except total WBC which decreased to slightly below baseline but was still within the normal reference range. CONCLUSIONS: A review of clinical cases, of ischemic or thrombotic events revealed no direct association with the CEW discharge. A full-trunk electrical weapon exposure did not lead to hematocyte changes beyond normal clinically expected variations in similar acute response scenarios. The case report and biomarker data do not support the hypothesis that a CEW discharge is associated with changes likely to promote coagulation or thrombus formation.

Evaluation of the CorInnova Heart Assist Device in an Acute Heart Failure Model.

While the number of patients supported with temporary cardiac assist is growing, the existing devices are limited by a multitude of complications, mostly related to contact with the blood. The CorInnova epicardial compressive heart assist device was tested in six sheep using an acute heart failure model. High esmolol dose, targeting a 50% reduction in CO from healthy baseline, resulted in a failure state with mean CO 1.9 L/min. Heart assist with the device during failure state resulted in an average absolute increase in CO of 1.0 L/min, along with a decline in ventricular work to 67.5% of the total LV SW. Combined with repeated success of minimally invasive device implant, the resulting increases in cardiac hemodynamics achieved while still unloading the heart demonstrate the potential of the CorInnova device for temporary heart assist.

Electrical weapons and excited delirium: shocks, stress, and serum serotonin.

It has been suggested that a CEW (conducted electrical weapon) exposure could elicit a stress response that could cause ExDS (excited delirium syndrome). There are some parallels between the signs of ExDS and serotonin syndrome (SS). Electroconvulsive therapy raises serotonin levels and therefore provides a plausible link between CEW applications and elevated serotonin levels. This study was designed to determine whether a CEW exposure elevates serum serotonin. A total of 31 police academy cadets were exposed to a very broad-spread 5-s CEW stimulus from a TASER brand X26 CEW. Blood was drawn before and after the exposure and at 24 h post exposure to measure serum serotonin levels. Lactic acid and cortisol levels were also compared. Median serum serotonin levels were 30 IQR (21,46), 36 IQR (22,50), and 32 IQR (21,45) ng/mL before exposure, after exposure, and 24 h after exposure (NS by pooled comparisons). The increase from baseline to post-test serotonin (∆ median = +6, ∆ mean = +2.7) ng/mL was not significant by a paired T-test (p = .29) but was significant by the Wilcoxon signed-rank test (p = .037). The increase to post-test log serotonin was not significant by a paired T-test (p = .13) but was significant by the Wilcoxon test (p = .049). All serotonin levels remained within the normal reference range of 0-200 ng/mL. Post-hoc analysis demonstrated that the study was powered to detect a ½ SD change, in log serotonin, with a 90% likelihood. With a very-broad electrode spread, CEW exposure did not significantly raise serum serotonin levels.

An experimental canine patent ductus arteriosus occlusion device based on shape memory polymer foam in a nitinol cage.

Patent ductus arteriosus (PDA) is a congenital cardiovascular defect in which a fetal connection between the aorta and pulmonary artery does not spontaneously close shortly after birth. If left uncorrected serious complications and even death can occur. Surgical ligation is the traditional treatment method; however, it is an invasive procedure, that motivates development of a minimally invasive option. Shape memory polymer (SMP) foams are unique materials that hold promise in the field of minimally invasive occlusion devices. In this work, a prototype nitinol foam cage (NFC) incorporating SMP foams has been designed and evaluated in multiple mechanical and in vitro verification tests. The NFC demonstrated acceptable fatigue resistance in a preliminary strut integrity test, withstanding one million cycles without complete strut fracture. Radial force analysis of both thick- and thin-walled prototype variations generated less vessel distension and wall tension in a vessel mimic compared to a commercial device. The NFCs exhibited negligible in vitro migration, comparable to that of a commercial device, using simplified, ideal models of PDA. Deployment characteristics of the prototypes were evaluated and compared to that of a commercial device when delivered into physiological models of PDA. During mock deployments, a veterinary cardiologist noted that, while deliverable, the thin-walled NFC prototype exhibited poor deployment characteristics, however the thick-walled NFC had deployment characteristics comparable to that of a commercial device. The promising results of this study warrant further investigation of the NFC device for canine PDA closure.

Incapacitation recovery times from a conductive electrical weapon exposure.

PURPOSE: Law enforcement officers expect that a TASER(®) CEW (Conducted Electrical Weapon) broad-spread probe exposure will temporarily incapacitate a subject who will then be able to immediately (~1 s delay) recover motor control in order to comply with commands. However, this recovery time has not been previously reported. METHODS: A total of 32 police academy students were exposed to a very broad-spread 5 s CEW stimulus as part of their training and told to depress a push-button as soon as they sensed the stimulus. A subgroup also depressed the push-button after being alerted by an audio stimulus. RESULTS: The response time after the audio trigger was 1.05 ± 0.25 s; the median was 1.04 s (range 0.69-1.34 s). For the paired CEW triggered group the mean response time was 1.41 ± 0.61 s with a median of 1.06 s (range 0.92-2.18 s), which was not statistically different. Only 2/32 subjects were able to depress the button during the CEW exposure and with delays of 3.09 and 4.70 s from the start. Of the remaining 30 subjects the mean response time to execute the task (once the CEW exposure ended) was 1.27 ± 0.58 s with a median of 1.19 s (range 0.31-2.99 s) (NS vs. the audio trigger). CONCLUSIONS: With a very-broad electrode spread, a CEW exposure could prevent or delay some purposeful movements. Normal reaction times appear to return immediately (~1 s) after the CEW exposure ceases.

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.

Efficient characterization of inhomogeneity in contraction strain pattern.

Cardiac dyssynchrony often accompanies patients with heart failure (HF) and can lead to an increase in mortality rate. Cardiac resynchronization therapy (CRT) has been shown to provide substantial benefits to the HF population with ventricular dyssynchrony; however, there still exists a group of patients who do not respond to this treatment. In order to better understand patient response to CRT, it is necessary to quantitatively characterize both electrical and mechanical dyssynchrony. The quantification of mechanical dyssynchrony via characterization of contraction strain field inhomogeneity is the focus of this modeling investigation. Raw data from a 3D finite element (FE) model were received from Roy Kerckhoffs et al. and analyzed in MATLAB. The FE model consisted of canine left and right ventricles coupled to a closed circulation with the effects of the pericardium acting as a pressure on the epicardial surface. For each of three simulations (normal synchronous, SYNC, right ventricular apical pacing, RVA, and left ventricular free wall pacing, LVFW) the Gauss point locations and values were used to generate lookup tables (LUTs) with each entry representing a location in the heart. In essence, we employed piecewise cubic interpolation to generate a fine point cloud (LUTs) from a course point cloud (Gauss points). Strain was calculated in the fiber direction and was then displayed in multiple ways to better characterize strain inhomogeneity. By plotting average strain and standard deviation over time, the point of maximum contraction and the point of maximal inhomogeneity were found for each simulation. Strain values were organized into seven strain bins to show operative strain ranges and extent of inhomogeneity throughout the heart wall. In order to visualize strain propagation, magnitude, and inhomogeneity over time, we created 2D area maps displaying strain over the entire cardiac cycle. To visualize spatial strain distribution at the time point of maximum inhomogeneity, a 3D point cloud was created for each simulation, and a CURE index was calculated. We found that both the RVA and LFVW simulations took longer to reach maximum contraction than the SYNC simulation, while also exhibiting larger disparities in strain values during contraction. Strain in the hoop direction was also analyzed and was found to be similar to the fiber strain results. It was found that our method of analyzing contraction strain pattern yielded more detailed spacial and temporal information about fiber strain in the heart over the cardiac cycle than the more conventional CURE index method. We also observed that our method of strain binning aids in visualization of the strain fields, and in particular, the separation of the mass points into separate images associated with each strain bin allows the strain pattern to be explicitly compartmentalized.

Estimation of aneurysm wall stresses created by treatment with a shape memory polymer foam device.

In this study, compliant latex thin-walled aneurysm models are fabricated to investigate the effects of expansion of shape memory polymer foam. A simplified cylindrical model is selected for the in-vitro aneurysm, which is a simplification of a real, saccular aneurysm. The studies are performed by crimping shape memory polymer foams, originally 6 and 8 mm in diameter, and monitoring the resulting deformation when deployed into 4-mm-diameter thin-walled latex tubes. The deformations of the latex tubes are used as inputs to physical, analytical, and computational models to estimate the circumferential stresses. Using the results of the stress analysis in the latex aneurysm model, a computational model of the human aneurysm is developed by changing the geometry and material properties. The model is then used to predict the stresses that would develop in a human aneurysm. The experimental, simulation, and analytical results suggest that shape memory polymer foams have potential of being a safe treatment for intracranial saccular aneurysms. In particular, this work suggests oversized shape memory foams may be used to better fill the entire aneurysm cavity while generating stresses below the aneurysm wall breaking stresses.

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

BACKGROUND: Much 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) Ht2, longer term stretch history Ht1, and time since the start of testing T. METHODS: A 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 Ht2, Ht1, and T are important factors for characterizing the inelastic deviation. For acquiring Ht2 and Ht1, 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. RESULTS: Inelastic 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, Ht2 and Ht1 were dominant. DISCUSSION: A 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.

Kinematics framework optimized for deformation, growth, and remodeling in vascular organs.

A basic tenant of constitutive theory is that phenomenological relations can be derivable from phenomenological behavior or material tests; and yet, conventional representation formulas, such as those of Rivlin and Fung, fail in this regard because of the choice of kinematical variables. Granted, with these representation formulas a particular constitutive relation may be guessed that fits data, but if the relation is non-unique and cannot be derived de novo from actual and/or hypothetical tests, then such a relation is indeterminable. The representation formula of Rivlin is indeterminable because of excessive covariance or coalignment in the kinematical variables. The representation formula of Fung is indeterminable because the incompressibility constraint is not utilized to reduce the kinematical variables a priori. The proposed kinematics framework succeeds in achieving determinability for hyperelastic materials because, primarily, the kinematical variables have minimal coalignment and dilatation and distortion are separated. Determinability is discussed and demonstrated in the context of hyperelasticity. However, any representation formula, whether it is for visco-elasticity or remodeling or etcetera, will be indeterminable when kinematical variables are highly coaligned and/or are subject to a non-reducible constraint. In other words, conventional kinematical frameworks are non-starters for experimentally determining constitutive representations for soft tissues. For the sake of determinability and/or validity of continuum models of vascular tissue, the proposed framework is needed. Moreover, this framework is optimized to simplify the balance equations for tubular structures.

Alterations in lateral left ventricular wall transmural strains during acute circumflex and anterior descending coronary occlusion.

BACKGROUND: Increased circumferential-radial shear in the midlateral left ventricle adjacent to ischemic myocardium has been observed during acute midcircumflex ischemia in open-chest animals. Extending this work, we studied transmural strains in closed-chest animals during acute proximal-circumflex (pCX) and proximal-left anterior descending (pLAD) occlusions. METHODS: Six sheep had radiopaque markers implanted to silhouette the left ventricle and measure regional systolic fractional area shortening; three transmural bead columns were inserted into the midlateral wall for transmural myocardial strain analysis. After 8 weeks, three-dimensional marker coordinates were obtained using biplane videofluoroscopy, both before and during separate 1-minute pLAD and pCX balloon occlusions. Systolic strains were assessed along circumferential, longitudinal, and radial axes, and then transformed into fiber strains using quantitative microstructural measurements. RESULTS: Acute pLAD occlusion and pCX occlusion caused similar hemodynamic insults. Systolic fractional area shortening revealed that the beads were in the ischemic territory during pCX occlusion, but adjacent to the ischemic myocardium during pLAD occlusion. Transmural circumferential strain and fiber shortening fell in the ischemic region during pCX occlusion, but remained normal when adjacent to the ischemic myocardium during pLAD occlusion. Circumferential-radial shear strain increased in the lateral left ventricle during pCX occlusion, but reversed in this same region during pLAD occlusion. Longitudinal-radial shear also decreased during pLAD occlusion. CONCLUSIONS: Reversal of lateral wall circumferential-radial shear and decreased longitudinal-radial shear during acute pLAD occlusion reflects altered mechanical interaction between ischemic and nonischemic myocardium. Increased circumferential-radial shear during pCX occlusion also reflects mechanical interaction. The direction of circumferential-radial shear deformation depends on the location of the adjacent ischemic territory.

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).

Transmural sheet strains in the lateral wall of the ovine left ventricle.

In an attempt to provide a better understanding of our finding that regions with contracting left ventricular myofibers need not develop a significant transmural systolic wall thickening gradient, the analytic approach of Costa et al. was applied to the four-dimensional dynamic data obtained 1 and 8 wk after surgical implantation of transmural radiopaque beads in the lateral equatorial left ventricular wall in seven ovine hearts. Quantitative histology of tissue blocks demonstrated that fiber angles varied linearly across the wall in this region from -37 degrees in the subepicardium to +18 degrees in the subendocardium. Sheet angles exhibited a pleated-sheet behavior, alternating sign from subepicardium to subendocardium. From end diastole (reference configuration) to end systole (deformed configuration), fiber strain was uniformly negative, sheet extension and sheet thickening were uniformly positive, and sheet-normal shear contributed to wall thickening at all wall depths. Subepicardial radial wall thickening increased significantly from week 1 to week 8, with significant increases in the contributions from subepicardial sheet extension and sheet-normal shear. At 1 and 8 wk, the contribution of sheet-normal shear to wall thickening was substantial at all transmural depths; the contribution of sheet extension to wall thickening was greatest in the subepicardium and least in the subendocardium, and the contribution of sheet thickening to wall thickening was greatest in the subendocardium and least in the subepicardium. A mechanistic model is proposed that provides a working hypothesis that a selective decrease in subepicardial intercellular matrix stiffness is responsible for elimination of the transmural wall thickening gradient 1-8 wk after marker implantation surgery.

Alterations in transmural strains adjacent to ischemic myocardium during acute midcircumflex occlusion.

OBJECTIVE: Helically oriented left ventricular fibers assemble into transmural sheets, which are important for wall-thickening mechanics: 15% fiber shortening results in 40% cross-fiber left ventricular wall thickening and a 60% ejection fraction through sheet extension, thickening, and shear. Normal cardiac microstructure and strains are optimized; deviations could result in apoptosis and deleterious matrix remodeling, which degenerates into global cardiomyopathy. We studied alterations in transmural strains adjacent to ischemic myocardium during acute midcircumflex occlusion. METHODS: Nine sheep had radiopaque markers implanted to measure left ventricular systolic fractional area shortening; 3 transmural bead columns were inserted into the midlateral wall for strain analysis. Three-dimensional marker coordinates were obtained with biplane videofluoroscopy before and during 70 seconds of ischemia. Systolic strains were quantified along circumferential, longitudinal, and radial axes (n = 9) and were transformed into fiber-sheet coordinates by using quantitative microstructural measurements (n = 5). RESULTS: A functional border was defined in the midlateral left ventricle; ischemia decreased posterolateral fractional area shortening, and anterolateral fractional area shortening increased. In this demarcation junction, subepicardial end-systolic radial wall thickening decreased (0.16 +/- 0.08 vs 0.11 +/- 0.06) and sheet-normal shear was abolished (0.08 +/- 0.04 vs -0.01 +/- 0.03). Longitudinal shortening decreased in the subepicardium and midwall (-0.05 +/- 0.04 vs +/- -0.01 +/- 0.06), but circumferential-radial shear increased at these depths (0.04 +/- 0.04 vs 0.11 +/- 0.05). Subendocardial fiber stretch occurred during early systole (-0.01 +/- 0.03 vs 0.02 +/- 0.03), and end-systolic fiber-sheet shear increased (0.07 +/- 0.01 vs 0.11 +/- 0.04, all P < .05). CONCLUSIONS: Increased circumferential-radial shear and altered fiber-sheet strains reflect mechanical interactions between ischemic and nonischemic myocardium, which might be important in triggering remodeling processes that evolve into global ischemic cardiomyopathy.

Transmural cardiac strains in the lateral wall of the ovine left ventricle.

The constant-volume property of contracting cardiac muscle has been invoked in models of heart wall mechanics that predict that systolic subendocardial left ventricular (LV) wall thickening must significantly exceed subepicardial thickening. To examine this prediction, we implanted arrays of radiopaque markers to measure lateral equatorial wall transmural strains and global and regional LV geometry in seven sheep and studied the four-dimensional dynamics of these arrays using biplane videofluoroscopy (60 Hz) in anesthetized intact animals 1 and 8 wk after surgery. A transmural gradient of systolic lateral wall thickening was observed at 1 wk (P = 0.009; linear regression) but was no longer present at 8 wk (P = 0.243). Referenced to end diastole, group mean (+/-SD) end-systolic radial subepicardial, midwall, and subendocardial wall thickening strains were, respectively, 0.08 +/- 0.08, 0.14 +/- 0.08, and 0.22 +/- 0.12 at 1 wk and 0.19 +/- 0.07 (P = 0.02; 1 vs. 8 wk), 0.20 +/- 0.04, and 0.23 +/- 0.07 at 8 wk. With the exception of an 8-ml (7%) increase in end-diastolic volume (P = 0.04) from 1 to 8 wk, LV shape and hemodynamics were otherwise unchanged. We conclude that equivalent hemodynamics can be generated by the left ventricle with or without a transmural gradient of systolic wall thickening in this region; thus such a gradient is unlikely to be a fundamental property of the contracting LV myocardium. We discuss some implications of these findings regarding mechanisms involved in systolic wall thickening.