Asynchrony of ventricular activation affects magnitude and timing of fiber stretch in late-activated regions of the canine heart

Abstract

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...

Cardiac resynchronization: Insight from experimental and computational models

“…These findings support an important role for effective local preload as the cause of the regional differences in contraction pattern during asynchronous activation. However, Coppola et al (2007) also found evidence that the increased systolic shortening in late activated regions may be due to decreased afterload.…”

Timing and magnitude of systolic stretch affect myofilament activation and mechanical work

“…While the increased work can mostly be explained by the time-varying elastance of cardiac muscle, the decreased work in muscles stretched after the peak of the Ca 2ϩ transient is largely due to myofilament deactivation. dyssynchrony; hypertrophy; muscle mechanics; papillary muscle; stretch DYSSYNCHRONOUS ELECTRICAL ACTIVATION of the ventricles, due to conduction defects such as left bundle branch block or ventricular pacing of structurally normal hearts, leads to abnormal systolic stretch (2). During ectopic ventricular pacing, early contraction near the pacing site stretches remote sites that have not yet begun to contract (17).…”

“…Because dyssynchronous systolic stretch is caused directly or indirectly by the contraction of earlier or later activated regions of the wall, its duration is relatively long and typically about half the normal systolic interval (2). Its magnitude and timing relative to local electrical activation depend on location relative to the stimulus site, with the largest and earliest systolic stretches occurring in the latest activated regions where premature lengthening has peaked and largely recovered by the time local depolarization occurs.…”

“…The aim of this study was to investigate the mechanical effects of acute systolic stretches (representative in timing and magnitude of those seen during dyssynchronous ventricular activation in vivo) on cardiac contractile mechanics and the mechanisms by which these physiological stretches alter tension development. Isolated mouse right ventricular (RV) papillary muscles were stretched to mimic the magnitude, timing, and duration of systolic fiber stretch observed during ventricular pacing in vivo (2). Since different regions of the ventricles experience different timings and magnitudes of systolic stretch, the effects of these variables on twitch tension and work were systematically investigated.…”

Myocardial Stretch in Early Systole is a Key Determinant of the Synchrony of Left Ventricular Mechanical Activity in vivo

“…Such electromechanical dispersion of contractile activity may affect LV function, resulting in global LV dyssynchrony 15 and systolic and diastolic dysfunction. 16 Accordingly, the optimization of electromechanical activity by improving pre-ejection shortening-stretch mechanics may influence global LV performance and explain the benefits of CRT.…”