OBJECTIVES We sought to resolve the 3-dimensional transmural heterogeneity in myocardial mechanics observed during the isovolumic contraction (IC) phase. BACKGROUND Although myocardial deformation during IC is expected to be little, recent tissue Doppler imaging studies suggest dynamic myocardial motions during this phase with biphasic longitudinal tissue velocities in left ventricular (LV) long-axis views. A unifying understanding of myocardial mechanics that would account for these dynamic aspects of IC is lacking. METHODS We determined the time course of 3-dimensional finite strains in the anterior LV of 14 adult mongrel dogs in vivo during IC and ejection with biplane cineradiography of implanted transmural markers. Transmural fiber orientations were histologically measured in the heart tissue postmortem. The strain time course was determined in the subepicardial, midwall, and subendocardial layers referenced to the end-diastolic configuration. RESULTS During IC, there was circumferential stretch in the subepicardial layer, whereas circumferential shortening was observed in the midwall and the subendocardial layer. There was significant longitudinal shortening and wall thickening across the wall. Although longitudinal tissue velocity showed a biphasic profile; tissue deformation in the longitudinal as well as other directions was almost linear during IC. Subendocardial fibers shortened, whereas subepicardial fibers lengthened. During ejection, all strain components showed a significant change over time that was greater in magnitude than that of IC. Significant transmural gradient was observed in all normal strains. CONCLUSIONS IC is a dynamic phase characterized by deformation in circumferential, longitudinal, and radial directions. Tissue mechanics during IC, including fiber shortening, appear uninterrupted by rapid longitudinal motion created by mitral valve closure. This study is the first to report layer-dependent deformation of circumferential strain, which results from layer-dependent deformation of myofibers during IC. Complex myofiber mechanics provide the mechanism of brief clockwise LV rotation (untwisting) and significant wall thickening during IC within the isovolumic constraint.

Despite lack of evidence of significant transmural gradient in electrical repolarization in vivo, there is transmural dispersion of myofiber relaxation as well as shortening.

The excitation-contraction coupling properties of cardiac myocytes isolated from different regions of the mammalian left ventricular wall have been shown to vary considerably, with uncertain effects on ventricular function. We embedded a cell-level excitation-contraction coupling model with region-dependent parameters within a simple finite element model of left ventricular geometry to study effects of electromechanical heterogeneity on local myocardial mechanics and global haemodynamics. This model was compared with one in which heterogeneous myocyte parameters were assigned randomly throughout the mesh while preserving the total amount of each cell subtype. The two models displayed nearly identical transmural patterns of fibre and cross-fibre strains at end-systole, but showed clear differences in fibre strains at earlier points during systole. Haemodynamic function, including peak left ventricular pressure, maximal rate of left ventricular pressure development and stroke volume, were essentially identical in the two models. These results suggest that in the intact ventricle heterogeneously distributed myocyte subtypes primarily impact local deformation of the myocardium, and that these effects are greatest during early systole.

Coppola BA, Covell JW, McCulloch AD, Omens JH. Asynchrony of ventricular activation affects magnitude and timing of fiber stretch in late-activated regions of the canine heart. Am J Physiol Heart Circ Physiol 293: H754-H761, 2007. First published April 20, 2007; doi:10.1152/ajpheart.01225.2006.-Abnormal electrical activation of the left ventricle results in mechanical dyssynchrony, which is in part characterized by early stretch of late-activated myofibers. To describe the pattern of deformation during "prestretch" and gain insight into its causes and sequelae, we implanted midwall and transmural arrays of radiopaque markers into the left ventricular anterolateral wall of open-chest, isoflurane-anesthetized, adult mongrel dogs. Biplane cineradiography (125 Hz) was used to determine the time course of two-and three-dimensional strains while pacing from a remote, posterior wall site. Strain maps were generated as a function of time. Electrical activation was assessed with bipolar electrodes. Posterior wall pacing generated prestretch at the measurement site, which peaked 44 ms after local electrical activation. Overall magnitudes and transmural gradients of strain were reduced when compared with passive inflation. Fiber stretch was larger at aortic valve opening compared with end diastole (P Ͻ 0.05). Fiber stretch at aortic valve opening was weakly but significantly correlated with local activation time (r 2 ϭ 0.319, P Ͻ 0.001). With a short atrioventricular delay, fiber lengths were not significantly different at the time of aortic valve opening during ventricular pacing compared with atrial pacing. However, ejection strain did significantly increase (P Ͻ 0.05). We conclude that the majority of fiber stretch occurs after local electrical activation and mitral valve closure and is different from passive inflation. The increased shortening of these regions appears to be because of a reduced afterload rather than an effect of lengthdependent activation in this preparation. ventricular pacing; mechanical activation; fiber stretch; dyssynchrony VENTRICULAR EPICARDIAL ACTIVATION results in a heterogeneous pattern of contraction such that the timing of the onset of local shortening mirrors the spread of the electrical depolarization wave front. As the region near the pacing site shortens, remote late-activated regions lengthen. Previous studies have observed this lengthening in late-activated regions, which has been termed "prestretch" by several investigators (2, 6, 16). These studies have used a wide variety of techniques, including ultrasonic crystals (2), surface markers (16), and magnetic resonance imaging (MRI; see Ref. 17) to quantify the prestretch. Most of these studies have shown augmented ejection shortening at late-activated sites relative to early activated sites, implying that prestretch may improve performance via muscle fiber length-dependent activation. However, they did not determine if prestretch is different from passive distension or assess its timing relative to ventricular pressure generation. M...