shortening deactivation
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A muscle undergoing cyclical contractions requires fast and efficient muscle activation and relaxation to generate high power with relatively low energetic cost. To enhance activation and increase force levels during shortening, some muscle types have evolved stretch activation (SA), a delayed increased in force following rapid muscle lengthening. SA's complementary phenomenon is shortening deactivation (SD), a delayed decrease in force following muscle shortening. SD increases muscle relaxation, which decreases resistance to subsequent muscle lengthening. While it might be just as important to cyclical power output, SD has received less investigation than SA. To enable mechanistic investigations into SD and quantitatively compare it to SA, we developed a protocol to elicit SA and SD from Drosophila and Lethocerus indirect flight muscles (IFM) and Drosophila jump muscle. When normalized to isometric tension, Drosophila IFM exhibited a 118% SD tension decrease, Lethocerus IFM dropped by 97%, and Drosophila jump muscle decreased by 37%. The same order was found for normalized SA tension: Drosophila IFM increased by 233%, Lethocerus IFM by 76%, and Drosophila jump muscle by only 11%. SD occurred slightly earlier than SA, relative to the respective length change, for both IFMs; but SD was exceedingly earlier than SA for jump muscle. Our results suggest SA and SD evolved to enable highly efficient IFM cyclical power generation and may be caused by the same mechanism. However, jump muscle SA and SD mechanisms are likely different, and may have evolved for a role other than to increase the power output of cyclical contractions.

AbstractThe linearity and load insensitivity of the end-systolic pressure–volume-relationship (ESPVR), a parameter that describes the ventricular contractile state, are controversial. We hypothesize that linearity is influenced by a variable overlay of the intrinsic mechanism of autoregulation to afterload (shortening deactivation) and preload (Frank-Starling mechanism). To study the effect of different short-term loading alterations on the shape of the ESPVR, experiments on twenty-four healthy pigs were executed. Preload reductions, afterload increases and preload reductions while the afterload level was increased were performed. The ESPVR was described either by a linear or a bilinear regression through the end-systolic pressure volume (ES-PV) points. Increases in afterload caused a biphasic course of the ES-PV points, which led to a better fit of the bilinear ESPVRs (r2 0.929 linear ESPVR vs. r2 0.96 and 0.943 bilinear ESPVR). ES-PV points of a preload reduction on a normal and augmented afterload level could be well described by a linear regression (r2 0.974 linear ESPVR vs. r2 0.976 and 0.975 bilinear ESPVR). The intercept of the second ESPVR (V0) but not the slope demonstrated a significant linear correlation with the reached afterload level (effective arterial elastance Ea). Thus, the early response to load could be described by the fixed slope of the ESPVR and variable V0, which was determined by the actual afterload. The ESPVR is only apparently nonlinear, as its course over several heartbeats was affected by an overlay of SDA and FSM. These findings could be easily transferred to cardiovascular simulation models to improve their accuracy.

The asynchronous muscles of insects are characterized by asynchrony between muscle electrical and mechanical activity, a fibrillar organization with poorly developed sarcoplasmic reticulum, a slow time course of isometric contraction, low isometric force, high passive stiffness and delayed stretch activation and shortening deactivation. These properties are illustrated by comparing an asynchronous muscle, the basalar flight muscle of the beetle Cotinus mutabilis, with synchronous wing muscles from the locust, Schistocerca americana. Because of delayed stretch activation and shortening deactivation, a tetanically stimulated beetle muscle can do work when subjected to repetitive lengthening and shortening. The synchronous locust muscle, subjected to similar stimulation and length change, absorbs rather than produces work.

The primary determinants of muscle force throughout a shortening-lengthening cycle, and therefore of the net work done during the cycle, are (1) the shortening or lengthening velocity of the muscle and the force-velocity relationship for the muscle, (2) muscle length and the length-tension relationship for the muscle, and (3) the pattern of stimulation and the time course of muscle activation following stimulation. In addition to these primary factors, there are what are termed secondary determinants of force and work output, which arise from interactions between the primary determinants. The secondary determinants are length-dependent changes in the kinetics of muscle activation, and shortening deactivation, the extent of which depends on the work that has been done during the preceding shortening. The primary and secondary determinants of muscle force and work are illustrated with examples drawn from studies of crustacean muscles.

Active shortening of respiratory muscle L2B from the crab Carcinus maenas results in contractile deactivation, seen as (1) a decline of force during the course of isovelocity shortening, (2) a reduction in the rate of force redevelopment following shortening, (3) a depression of the level of isometric force reached following shortening, and (4) an accelerated relaxation at the end of stimulation. The degree of deactivation increases with increasing distance of shortening, decreases with increasing shortening velocity, and is approximately linearly related to the work done during shortening. Deactivation lasts many seconds if stimulation is maintained, but is largely although not completely removed if the stimulation is temporarily interrupted so that the force drops towards the resting level. Deactivation for a given distance and velocity of shortening increases with increasing muscle length above the optimum length for force production. Stimulating muscle L2B at suboptimal frequencies gives tetanic contractions that are fully fused but of less than maximal amplitude. The depression of force following shortening, relative to the force during an isometric contraction, is independent of the stimulus frequency used to activate the muscle, indicating that deactivation is not a function of the background level of stimulus-controlled muscle activation upon which it occurs. Deactivation reduces the work required to restretch a muscle after it has shortened, but it also lowers the force and therefore the work done during shortening. The net effect of deactivation on work output over a full shortening/lengthening cycle is unknown.

We characterized the design of the frog muscular system for jumping by comparing the properties of isolated muscle with the operating conditions of muscle measured during maximal jumps. During jumping, the semimembranosus muscle (SM) shortened with a V/Vmax (where V is shortening velocity and Vmax is maximal shortening velocity) where 90 and 100% of maximal power would be generated at 15 and 25 degrees C, respectively. To assess the level of activation during jumping, the SM was driven through the in vivo length change and stimulus conditions while the resulting force was measured. The force generated under the in vivo conditions at both temperatures was at least 90% of the force generated at that same V under maximally activated conditions. Thus the SM was nearly maximally activated, and shortening deactivation was minimal. The initial sarcomere length and duration of the stimulus before shortening were important factors that minimized shortening deactivation during jumping. Thus the frog muscular system appears to be designed to meet the three necessary conditions for maximal power generation during jumping: optimal myofilament overlap, optimal V/Vmax, and maximal activation.

A formula was derived from an active cross-bridge model for expressing the "time-varying myocardial elastance" of the left ventricular (LV) wall. To assess the validity of this model's predictions of the behavior of the intact left ventricle, eight healthy beagles were instrumented with ultrasonic crystals to measure LV diameter and a micromanometer for LV pressure measurement. During ejecting beats starting from short end-diastolic myocardial lengths, the predicted values for myocardial elastance and force closely approximated the measured values for the instantaneous external load-muscle length ratio and the external load, respectively. However, in cycles starting from long end-diastolic lengths, the predicted myocardial elastance and force values deviated from the actual values during the shortening phase of LV contraction. The differences between myocardial elastance and external load-muscle length ratio as well as those between force and external load during the shortening phase (shortening deactivation) appeared to result from an internal load in the shortening myocardium that was closely related to the product of instantaneous myocardial force and shortening velocity. Thus this model may provide reasonable approximations of myocardial elastance and force in the intact LV wall. In addition, time-varying myocardial elastance might reflect time-dependent changes in calcium activation.

We reanalyzed experiments in in situ hearts of 16 open-chest anesthetized dogs, in which two different loading interventions were performed, i.e., an occlusion of the descending aorta (InP) and a rapid volume infusion (InV). Previous studies had demonstrated that the end-systolic elastance (Ees) of the InP was substantially larger than the Ees of the InV suggesting either a load dependency of Ees as such, or an increase in contractility during InP. The data were reanalyzed in the light of the muscular pump concept by plotting peak normalized velocity of circumferential shortening versus a global representative force approximating the left ventricle by a sphere. In all but one experiment the points of the two interventions are located on a single relationship over a very broad range of forces (from 397 to 2,461 g between the control states of experiments and from 602 to 3,278 g difference between control and highest load within experiments). The virtual independence of the force-velocity relation (FVR) and the dependence of the end-systolic pressure-volume relation (ESPVR) on the type of loading intervention can be ascribed to the fact that the former is assessed early during ejection and is therefore less influenced by shortening deactivation and internal resistance than the ESPVR. We conclude that the FVR offers a more consistent characterization of intrinsic LV function than the ESPVR.