Theory of cardiac sarcomere contraction and the adaptive control of cardiac function to changes in demands

Abstract

This chapter explores the adaptive control of cardiac function by the loading conditions and relates the observed phenomena to our theory of the sarcomeric control of contraction. Our theory includes two feedback mechanisms: cooperativity-regulated cross-bridge recruitment and energy consumption, and mechanical feedback that determines the interplay between the external work and the force-time integral. The latter also suggests that cardiac efficiency is load independent. This paper explores the regulation of cardiac function by loading conditions, and the role of afterload in adult sheep in situ (n=8). Different afterloads were imposed by partial aortic occlusions. Transient inferior vena cava occlusions (IVCOs) were pre-formed at each steady afterload. A novel, highly linear relationship was found between the external work and pressure-time integral during each transient IVCO at constant afterload. Of interest, the slope of this relationship was afterload-dependent also during fast transient changes in the afterload. These observations are congruent with the suggested adaptive sarcomeric control of contraction, and may provide a powerful tool for quantifying cardiac function.

Permanent Cardiac Sarcomere Changes in a Rabbit Model of Intrauterine Growth Restriction

“…The shorter sarcomere and thick-thin filament interaction length might indicate a decrease in the number of binding events for cross-bridges between actin and myosin. Since cardiac muscle energy consumption depends on the number of recruited cross-bridges [40] shorter sarcomere length and thick-thin filament interaction length could be interpreted as an adaptive mechanism to cope with the oxygen and/or glucose restriction in IUGR. Importantly, in this study we show evidence of the postnatal persistence of the changes on sarcomere morphometry, which can not be assessed in humans.…”

Myocardial Contractility: Historical and Contemporary Considerations

“…Subsequent research has provided excellent descriptions of cardiac muscle cell electrophysiology, [Ca +2 ] i cycling (calcium induced-calcium release) and the sequence of processes responsible for cardiac muscle contraction (excitation-contraction coupling) (Bers, 2008;Janssen, 2010;Chung et al, 2015;Sequeira and van der Velden, 2015;Eisner et al, 2017;Sweeney and Hammers, 2018). Current investigations of cardiac muscle contraction are focused on the biochemistry (i.e., chemo-mechanical cycle), mechanosensing and kinetic behavior of sarcomeric proteins since it is generally believed that cardiac muscle contraction: "has its roots in the individual molecular motors working in every muscle cellthe myosin molecule" (Hinken and Solaro, 2007;Janssen, 2010Janssen, , 2019Sela et al, 2010;Stehle and Iorga, 2010;Spudich, 2011;Sung et al, 2015;Liu et al, 2018;Mamidi et al, 2019). This perspective provides historical and contemporary evidence for conveying definitions of the terms cardiac performance, inotropy and contractility.…”