title: Timing and magnitude of systolic stretch affect myofilament activation and mechanical work.
abstract: 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(2+) 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(2+) 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(2+) transient is largely due to myofilament deactivation.
authors.affiliation: Department of Bioengineering, University of California-San Diego, La Jolla, California;
authors.forename: Jared R
authors.initials: JR
authors.lastname: Tangney
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Connecticut; and.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Campbell
authors.affiliation: Department of Bioengineering, University of California-San Diego, La Jolla, California; Department of Medicine, University of California-San Diego, La Jolla, California.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCulloch
authors.affiliation: Department of Bioengineering, University of California-San Diego, La Jolla, California; Department of Medicine, University of California-San Diego, La Jolla, California jomens@ucsd.edu.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Omens
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D020013:Calcium Signaling; D004548:Elasticity; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D008297:Male; D057507:Mice, 129 Strain; D008955:Models, Cardiovascular; D053580:Muscle Strength; D009210:Myofibrils / Q000502:physiology*; D010210:Papillary Muscles / Q000502:physiology*; D013599:Systole; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology; D016278:Ventricular Function, Right
keywords: dyssynchrony; hypertrophy; muscle mechanics; papillary muscle; stretch