The contractile adaption to preload depends on the amount of afterload

Abstract

AimsThe Frank–Starling mechanism (rapid response (RR)) and the secondary slow response (SR) are known to contribute to increases contractile performance. The contractility of the heart muscle is influenced by pre‐load and after‐load. Because of the effect of pre‐load vs. after‐load on these mechanisms in not completely understood, we studied the effect in isolated muscle strips.Methods and resultsProgressive stretch lead to an increase in shortening/force development under isotonic (only pre‐load) and isometric conditions (pre‐ and after‐load). Muscle length with maximal function was reached earlier under isotonic (L max‐isotonic) compared with isometric conditions (L max‐isometric) in nonfailing rabbit, in human atrial and in failing ventricular muscles. Also, SR after stretch from slack to L max‐isotonic was comparable under isotonic and isometric conditions (human: isotonic 10 ± 4%, isometric 10 ± 4%). Moreover, a switch from isotonic to isometric conditions at L max‐isometric showed no SR proving independence of after‐load. To further analyse the degree of SR on the total contractile performance at higher pre‐load muscles were stretched from slack to 98% L max‐isometric under isotonic conditions. Thereby, the SR was 60 ± 9% in rabbit and 51 ± 14% in human muscle strips.ConclusionsThis work shows that the acute contractile response largely depends on the degree and type of mechanical load. Increased filling of the heart elevates pre‐load and prolongs the isotonic part of contraction. The reduction in shortening at higher levels of pre‐load is thereby partially compensated by the pre‐load‐induced SR. After‐load shifts the contractile curve to a better ‘myofilament function’ by probably influencing thin fibers and calcium sensitivity, but has no effect on the SR.

Non-linearity of end-systolic pressure–volume relation in afterload increases is caused by an overlay of shortening deactivation and the Frank–Starling mechanism

“…Thus, the manipulation of the loading condition during ejection, which affects the ejection velocity, also affects the pressure generation and the end-systolic pressure volume relation 39 . These findings are supported by the work of Schotola et al 40 , who investigated the effects of afterload and preload on force generation in isolated heart muscle preparations of rabbits. Accordingly, the response to preload alterations is modulated by the afterload level.…”

Haemodynamic parameters in postmenopausal women – beneficial effect of moderate continuous exercise training

“…Due to the Frank-Starling law, this increase in the preload causes an increase in SI, as described elsewhere [37,38]. With increasing end diastolic volume, the tension in the ventricle wall, and in consequence the sensitivity to calcium of the contractile proteins rise, physiologically resulting in a higher stroke index [39]. It is worth mentioning that all the measurements of preload were within the physiological ranges.…”

Myocardial Contractility: Historical and Contemporary Considerations

“…Factors that modulate the heart's ability to pump blood (i.e., perform) include heart rate (Bristow et al, 1963;Ceconi et al, 2011), loading conditions (i.e., preload, afterload) (Milnor, 1975;Norton, 2001;Skrzypiec-Spring et al, 2007;Milan et al, 2011;Westerhof and Westerhof, 2013;O'Rourke et al, 2016), the myosin molecules contractile state (Spudich, 2011), ventricular geometry (Lieb et al, 2014), elastance (i.e., stiffness) (Fry et al, 1964;Gaasch et al, 1976;Suga et al, 1980;Sagawa, 1981;Suga, 1990;Palladino et al, 1998;Zhong et al, 2005;Campbell et al, 2008;Walley, 2016;Kerkhof et al, 2018), ventricular-vascular coupling (Kass and Kelly, 1992;Antonini-Canterin et al, 2013;Walley, 2016) and prevailing neurohumoral activity, especially sympathetic-parasympathetic tone (Thomas, 2011;Gordan et al, 2015). Changes in preload and afterload have been described as "preload reserve" and "afterload matching, " respectively (Brutsaert and Sonnenblick, 1973;Ross et al, 1976;Ross, 1983;Walley, 2016;Schotola et al, 2017;Boudoulas et al, 2018). Key determinants of pump performance include heart rate, preload (volume of blood within a chamber), afterload (hindrance to ejection), and contractility.…”

“…Inotropy is muscle fiber length dependent and is modified by heterometric autoregulation [Cyon-Frank-Starling mechanism (Zimmer, 1998(Zimmer, , 2002Katz, 2002;Amiad and Landesberg, 2016;Sequeira and van der Velden, 2017)], homeometric autoregulation [von Anrep effect in vivo; slow force response in vitro (Sarnoff et al, 1960;Cingolani et al, 2013;Clancy et al, 1968;Furst, 2015;Schotola et al, 2017)], the force-frequency relationship [Bowditch, treppe, staircase effect, chronotropicinotropy (Bowditch, 1871;Noble et al, 1966;Anderson et al, 1973;Higgins et al, 1973;Gwathmey et al, 1990;Ross et al, 1995;Endoh, 2004;Janssen and Periasamy, 2007;Janssen, 2010;Puglisi et al, 2013)], and autonomic activity (Glick and Braunwald, 1965;Thames and Kontos, 1970;Ross et al, 1995). Inotropy decreases almost instantly, within one heartbeat, when parasympathetic activity increases, and more slowly, over 6-8 s, when sympathetic efferent activity changes (Olshansky et al, 2008).…”

“…It represents a unique and intrinsic ability of cardiac muscle (contracting at a fixed heart rate) to generate a force that is independent of any load or stretch applied" (Wijayasiri et al, 2012). Integral to all current definitions of the term contractility is the tacit requirement that it is independent of loading conditions (Braunwald, 1971;Davidson et al, 1974;Katz, 1983;Kass et al, 1987;Penefsky, 1994;Bombardini, 2005;Schotola et al, 2017)…”