Dissociation of force decline from calcium decline by preload in isolated rabbit myocardium

Abstract

It is well known that the rate of intracellular calcium ([Ca2+]i) decline is an important factor governing relaxation in unloaded myocardium. However, it remains unclear to what extent, under near physiological conditions, the intracellular calcium transient amplitude and kinetics contribute to the length-dependent increase in force and increase in duration of relaxation. We hypothesize that myofilament properties rather than calcium transient decline primarily determines the duration of relaxation in adult mammalian myocardium. To test this hypothesis, we simultaneously measured force of contraction and calibrated [Ca2+]i transients in isolated, thin rabbit trabeculae at various lengths at 37 degrees C. Time from peak tension to 50% relaxation (RT50(tension)) increases significantly with length (from 49.8+/-3.4 to 83.8+/-7.4 ms at an [Ca2+]o of 2.5 mM), whereas time from peak calcium to 50% decline (RT50(calcium)) was not prolonged (from 124.8+/-5.3 to 107.7+/-11.4 ms at an [Ca2+]o of 2.5 mM). Analysis of variance revealed that RT50(tension) is significantly correlated with length (P<0.0001). At optimal length, varying the extracellular calcium concentration increased both developed force and calcium transient amplitude, but RT50(tension) remained unchanged (P=0.90), whereas intracellular calcium decline actually accelerated (P<0.05). Thus, an increase in muscle length will result in an increase in both force and duration of relaxation, whereas the latter is not primarily governed by the rate of [Ca2+]i decline.

Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

“…Likewise, in rabbit muscles at 1, 2.5, and 4 mM bathing Ca 2ϩ , a similar kinetic balance was found (Ref. 27; Fig. 5).…”

Preload-induced changes in isometric tension and [Ca2+]i in rat myocardium

“…Similar findings were made in numerous studies on warm-blooded animal and human myocardium [9,[16][17][18][19][20][21][22][23][24]. The preload-induced interplay between cytosolic calcium and force development is thought to be indirect and most likely involves cooperative effects of association/dissociation of Ca-TnC [2,4,6,7,30,31].…”

“…The higher preload the larger amplitude of Ca 2+ transient has been observed in mouse [9], cat [18], rat [16,17,19] and rabbit [20,21] [18]. In contrast, no preload-dependent changes in Ca 2+ transient amplitude have been shown in ferret [22], rat [18,23] and human myocardium [24] while marked increase of peak isometric force was observed in all the cases.…”

“…The rate of the Ca 2+ transient decline in the initial phase was strengthened by increasing of [Ca 2+ ] o [22,28]. However, no evidence of preload effect on the rate or total duration of Ca 2+ transient decline was found in rabbit trabeculae [21] and Guinea-pig ventricular myocytes [29].…”

Cardiovascular Mechanics

“…Active material parameters are in part adapted from [60] [42], the parameters for the active state are adapted from [60], and the pressure term is chosen to give a realistic pressure-volume response. to achieve an electro-mechanical delay of 110 ms between the peak action potential and the peak active stress [149], which leads the parameter relation of the delay function to be ε ∞ = ε 0 /10. The pressure parameters (see Section 4.2.6) are tuned such that realistic pressure-volume loops are obtained, and to keep the pressure calculations numerically stable.…”