Simultaneous determination of regional left ventricular wall stresses in intact canine hearts

Von Hans Walte

The effect of pure mitral regurgitation on mitral annular geometry and three-dimensional saddle shape

ObjectiveChronic ischemic mitral regurgitation is associated with mitral annular dilatation in the septal-lateral dimension and flattening of the annular 3-dimensional saddle shape. To examine whether these perturbations are caused by the ischemic insult, mitral regurgitation, or both, we investigated the effects of pure mitral regurgitation (low pressure volume overload) on annular geometry and shape.MethodsEight radiopaque markers were sutured evenly around the mitral annulus in sheep randomized to control (CTRL, n = 8) or experimental (HOLE, n = 12) groups. In HOLE, a 3.5- to 4.8-mm hole was punched in the posterior leaflet to generate pure mitral regurgitation. Four-dimensional marker coordinates were obtained radiographically 1 and 12 weeks postoperatively. Mitral annular area, annular septal-lateral and commissure–commissure dimensions, and annular height were calculated every 16.7 ms.ResultsMitral regurgitation grade was 0.4 ± 0.4 in CTRL and 3.0 ± 0.8 in HOLE (P < .001) at 12 weeks. End-diastolic left ventricular volume index was greater in HOLE at both 1 and 12 weeks; end-systolic volume index was larger in HOLE at 12 weeks. Mitral annular area increased in HOLE predominantly in the commissure–commissure dimension, with no difference in annular height between HOLE versus CTRL at 1 or 12 weeks, respectively.ConclusionIn contrast with annular septal-lateral dilatation and flattening of the annular saddle shape observed with chronic ischemic mitral regurgitation, pure mitral regurgitation was associated with commissure–commissure dimension annular dilatation and no change in annular shape. Thus, infarction is a more important determinant of septal-lateral dilatation and annular shape than mitral regurgitation, which reinforces the need for disease-specific designs of annuloplasty rings

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine

2 ME338A -Homework Heterogeneity of Left Ventricular Wall Thickening Mechanisms

In spite of tremendous improvements during the past 20 years, heart failure remains one of the most common, costly, disabling, and deadly medical conditions affecting more than 25 million people worldwide. Despite the wide variety of pharmacological, surgical, device, and tissue engineered treatment strategies currently under investigation, patients with heart failure continue to experience progressive worsening of symptoms, frequent admission to the hospital, and premature death. Surgical strategies to reverse strain abnormalities in the ventricular wall are currently being recognized as a new paradigm for preventing the progression of heart failure. In an attempt to quantify strain profiles in the beating heart, researchers in the lab of Prof. D. Craig Miller in the Department of Cardiothoracic Surgery in the School of Medicine at Stanford have developed a novel technique to measure infarct-induced changes of ventricular wall kinematics in ovine models. They inserted two transmural beadsets, one in the anterior basal and one in the lateral lateral equatorial left ventricular wall, and silhouetted the left ventricular chamber with an additional thirteen subepicardial markers as illustrated in The overall objective is this homework is to determine the muscle fiber contraction during systole. This is pretty straightforward if you solve the following substeps! [1] Determine three vectors dX i that span the tetrahedron at end diastole. Take an arbitrary point of the tetrahedron as origin, e.g., X 1 , and calculate the three vectors dX 2 , dX 3 , and dX 4 from the origin to any other point using the coordinates X at end diastole such that dX i = X i − X 1 for i = 2, 3, 4. [2] Determine the same three vectors dx i that span the tetrahedron at end systole. Take the same point as origin, e.g., x 1 , and calculate the vectors dx 2 , dx 3 , and dx 4 from the origin to any other point using the coordinates x at end systole such that dx i = x i − x 1 for i = 2, 3, 4. [3] Determine the deformation gradient tensor F that maps all diastolic line elements as dX i onto the systolic line elements dx i . F = ∂x / ∂X is called the deformation gradient and it is the key kinematic quantity to [5] Determine the systolic fiber direction n fib = F · N fib . The deformation gradient can be used to map the measured diastolic fiber direction N fib onto the systolic fiber direction n fib . Determine n fib and comment on how N fib and n fib deviate. [6] Determine the fiber stretch λ = √ n fib · n fib . Since the fiber orientation N fib was given as a unit vector, the length of the systolic vector n fib = F · N fib corresponds to the relative change in fiber length, i.e., the fiber stretch in the finite strain setting, [7] Determine the second order Green Lagrange strain tensor E = 1 2 [ F t · F − I ] E is called the Green Lagrange strain tensor and it is used to characterize strains in the undeformed configuration in a finite strain setting. [8] Determine the displacement gradient tensor H = F − I. H = ∇u is the nonsymmetric displacement gradient tensor which can also be ex- [9] Linearize the Green Lagrange strain tensor E with the help of the Gateaux derivative to obtain the small strain tensor = 1 2 (H + H t ). Linearize E formally, then calculate , compare the small strain approximation with the large strain Green Lagrange tensor E, and comment on your results. [10] Determine the volume dilation e = tr( ). Comment on whether the tissue behaves compressible or incompressible and on whether this was what you would have expected. [11] Last, determine the normal strain n = N fib · · N fib . Compare the large strain fiber stretch λ with the small strain approximation of the fiber contraction n . Comment on your results. Do you think they are reasonable? Find evidence in the literature about the amount of maximum cardiomyocyte contraction. You can use MATLAB to solve the matrix and vector operations. If you choose to do so, you must deliver a printout of you MATLAB code with the homework. Background-Myocardial fibers are grouped into lamina (or sheets) 3 to 4 cells thick. Fiber shortening produces systolic left ventricular (LV) wall thickening primarily by laminar extension, thickening, and shear, but the regional variability and transmural distribution of these 3 mechanisms are incompletely understood. Methods and Results-Nine sheep had transmural radiopaque markers inserted into the anterior basal and lateral equatorial LV. Four-dimensional marker dynamics were studied with biplane videofluoroscopy to measure circumferential, longitudinal, and radial systolic strains in the epicardium, midwall, and endocardium. Fiber and sheet angles from quantitative histology allowed transformation of these strains into transmural contributions of sheet extension, thickening, and shear to systolic wall thickening. At all depths, systolic wall thickening in the anterior basal region was 1.6 to 1.9 times that in the lateral equatorial region. Interestingly, however, systolic fiber shortening was identical at each transmural depth in these regions. Endocardial anterior basal sheet thickening was Ͼ2 times greater than in the lateral equatorial region (epicardium, 0.16Ϯ0.15 versus 0.03Ϯ0.06; endocardium, 0.45Ϯ0.40 versus 0.17Ϯ0.09). Midwall sheet extension was Ͼ2 times that in the lateral wall (0.22Ϯ0.12 versus 0.09Ϯ0.06). Epicardial and midwall sheet shears in the anterior wall were Ϸ2 times higher than in the lateral wall (epicardium, 0.14Ϯ0.07 versus 0.05Ϯ0.03; midwall, 0.21Ϯ0.12 versus 0.12Ϯ0.06). Conclusions-These data demonstrate fundamentally different regional contributions of laminar mechanisms for amplifying fiber shortening to systolic wall thickening. Systolic fiber shortening was identical at each transmural depth in both the anterior and lateral LV sites. However, systolic wall thickening of the anterior site was much greater than that of the lateral site. Fiber shortening drives systolic wall thickening, but sheet dynamics and orientations are of great importance to systolic wall thickening. LV wall thickening and its clinical implications pivot on different wall thickening mechanisms in various LV regions. Attempts to implant healthy contractile cells into diseased hearts or to surgically manipulate LV geometry need to take into account not only cardiomyocyte contraction but also transmural LV intercellular architecture and geometry. (Circulation. 2008;118:713-721.

Three-dimensional regional dynamics of the normal mitral anulus during left ventricular ejection

AbstractThe mitral anulus is a dynamic structure that undergoes alterations in size and shape throughout the cardiac cycle, contracting during systole. Numerous reports have shown this systolic orifice reduction to be due chiefly to posterior annular contraction, whereas the anterior perimeter was unchanged. Segmental motion of the mitral anulus from true in vivo three-dimensional data, however, has not been described. We used radiopaque markers and simultaneous biplane videofluoroscopy to measure the lengths of mitral anular segments in seven closed-chest, sedated dogs. Eight markers were placed equidistant from each other around the mitral anulus. As viewed from the left atrium, segment 1 began at the posteromedial commissure, and the remaining segments were numbered sequentially clockwise around the anulus (that is, the posterior mitral anulus encompassed segments 1 to 4 and the anterior anulus encompassed segments 5 to 8). Marker image coordinates obtained from two orthogonal views 7 to 12 days after implantation were merged to construct three-dimensional marker coordinates at end-diastole and end-systole. From end-diastole to end-systole, mean annular area decreased by 11% ± 8% (5.5 ± 0.9 cm 2 to 4.9 ± 0.8 cm 2 , p = 0.005) and perimeter by 5% ± 4% (8.8 ± 0.7 cm to 8.3 ± 0.7 cm, p < 0.01). Mitral annular segmental percent systolic shortening (negative values indicate lengthening) were as follows (mean ± standard deviation): segment 1, 7% ± 9%; segment 2, 8% ± 10%; segment 3, 16% ± 6%; segment 4, 10% ± 7%; segment 5, -4% ± 5%; segment 6, -7% ± 7%; segment 7, 3% ± 2%; and segment 8, 6% ± 5%. With the exception of segment 1, all posterior (2 to 4) and two anterior (7 and 8) mitral annular segments contracted significantly ( p ≤ 0.05 vs zero, paired t test). Two anterior annular segments (5 and 6, regions overlapping aortic-mitral continuity), however, unexpectedly lengthened during left ventricular systole. We conclude that the anterior mitral anulus may be a much more dynamic component of the mitral apparatus that previously thought. Such heterogeneous dynamic annular motion should be taken into account when various mitral valve reparative techniques are being designed. (J T HORAC CARDIOVASC SURG 1996;111:574-85

Does septal-lateral annular cinching work for chronic ischemic mitral regurgitation?

AbstractObjectivesRing annuloplasty, the current treatment of choice for chronic ischemic mitral regurgitation, abolishes dynamic annular motion and immobilizes the posterior leaflet. In a model of chronic ischemic mitral regurgitation, we tested septal-lateral annular cinching aimed at maintaining normal annular and leaflet dynamics.MethodsTwenty-five sheep had radiopaque markers placed on the mitral annulus and anterior and posterior mitral leaflets. A transannular suture was anchored to the midseptal mitral annulus and externalized through the midlateral mitral annulus. After 7 days, biplane cinefluoroscopy provided 3-dimensional marker data (baseline) prior to creating inferior myocardial infarction by snare occlusion of obtuse marginal branches. After 7 weeks, the 9 animals that developed chronic ischemic mitral regurgitation were restudied before and after septal-lateral annular cinching. Anterior and posterior mitral leaflet angular excursion and annular septal-lateral and commissure–commissure dimensions and percent shortening were computed.ResultsSeptal-lateral annular cinching reduced septal-lateral dimension (baseline: 3.0 ± 0.2; chronic ischemic mitral regurgitation: 3.5 ± 0.4 [P < .05 vs baseline by repeated measures analysis of variance and Dunnett's test]; septal-lateral annular cinching: 2.4 ± 0.3 cm; maximum dimension) and eliminated chronic ischemic mitral regurgitation (baseline: 0.6 ± 0.5; chronic ischemic mitral regurgitation: 2.3 ± 1.0 [P < .05 vs baseline by repeated measures analysis of variance and Dunnett's test]; septal-lateral annular cinching: 0.6 ± 0.6; mitral regurgitation grade [0 to 4+]) but did not alter dynamic annular shortening (baseline: 7 ± 3; chronic ischemic mitral regurgitation: 10 ± 5; septal-lateral annular cinching: 6 ± 2, percent septal-lateral shortening) or posterior mitral leaflet excursion (baseline: 46° ± 8°; chronic ischemic mitral regurgitation: 41° ± 13°; septal-lateral annular cinching: 46° ± 8°).ConclusionsIn this model, septal-lateral annular cinching decreased chronic ischemic mitral regurgitation, reduced annular septal-lateral diameter (but not commissure–commissure diameter), and maintained normal annular and leaflet dynamics. These findings provide additional insight into the treatment of chronic ischemic mitral regurgitation