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

Abstract

Tangney JR, Campbell SG, McCulloch AD, Omens JH. Timing and magnitude of systolic stretch affect myofilament activation and mechanical work. Am J Physiol Heart Circ Physiol 307: H353-H360, 2014. First published May 30, 2014 doi:10.1152/ajpheart.00233.2014.-Dyssynchronous activation of the heart leads to abnormal regional systolic stretch. In vivo studies have suggested that the timing of systolic stretch can affect regional tension and external work development. In the present study, we measured the direct effects of systolic stretch timing on the magnitude of tension and external work development in isolated murine right ventricular papillary muscles. A servomotor was used to impose precisely timed stretches relative to electrical activation while a force transducer measured force output and strain was monitored using a charge-couple device camera and topical markers. Stretches taking place during peak intracellular Ca 2ϩ statistically increased peak tension up to 270%, whereas external work due to stretches in this interval reached values of 500 J/m. An experimental analysis showed that time-varying elastance overestimated peak tension by 100% for stretches occurring after peak isometric tension. The addition of the force-velocity relation explained some effects of stretches occurring before the peak of the Ca 2ϩ transient but had no effect in later stretches. An estimate of transient deactivation was measured by performing quick stretches to dissociate cross-bridges. The timing of transient deactivation explained the remaining differences between the model and experiment. These results suggest that stretch near the start of cardiac tension development substantially increases twitch tension and mechanical work production, whereas late stretches decrease external 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). Transient stretching of lateactivated regions has been referred to as "prestretch" (1,5,12) and can reach magnitudes of up to 20% (20). Conversely, early activated sites shorten prematurely and stretch during ejection (8). Dyssynchronous activation due to ventricular pacing of the normal heart also results in regionally heterogeneous distributions of local myocardial work (4, 13), O 2 uptake, myocardial blood flow (4) and, if sustained, asymmetric hypertrophy (19).Because dyssynchronous systolic stretch is caused directly or indirectly by the contraction of earlier or later activated regions of the wall, its duration is...

The role of pacing rate in the modulation of mechano-induced immediate and delayed changes in the force and Ca-transient of cardiac muscle

“…6D). This agrees with findings that the dynamical change in sarcomere length, not the length per se, is important in the regulation of myocardial contractility (Tangney et al, 2014;Kobirumaki-Shimozawa et al, 2016). The slow inotropic response may reflect the combined effects of increased Ca 2þ -buffering by TnC via length-induced increase in Ca 2þ sensitivity and tensionassociated effects on thin filaments (Dobesh et al, 2002;Dupuis et al, 2018;Li et al, 2019) and slow equilibration of Ca 2þ content between the main Ca 2þ buffers (Trafford et al, 2001;Louch et al, 2012).…”

Multiphysics and multiscale modelling, data–model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics

“…Nevertheless, an important motivation for a more refined microscopic model resides in the shorter time scale effects observed in fast transients, such as under force or length clamp [ 189 , 198 ]. In addition, transient deactivation may be a critical determinant of mechanical heterogeneity in asynchronous activation [ 199 ].…”

How myofilament strain and strain rate lead the dance of the cardiac cycle

“…For example, nonuniform segmental strains have also long been thought to help modify relaxation [33] but, as noted above, non-uniform strain of small segments (individual sarcomeres) is responsible for the fast phase of myofibril relaxation [13]. In the whole heart, it is unclear how much nonuniform strain might benefit cardiac function instead of representing pathological dyssynchrony, where ill-timed strain reduces force generation [57]. Thus, myofiber directed strain might provide a measure of dyssynchrony throughout the cardiac cycle, in addition to the Tissue Doppler Imaging measurement proposed for isovolumic contraction [18].…”