The contractile adaption to preload depends on the amount of afterload.

AIMS: The 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 RESULTS: Progressive 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 (Lmax-isotonic ) compared with isometric conditions (Lmax-isometric ) in nonfailing rabbit, in human atrial and in failing ventricular muscles. Also, SR after stretch from slack to Lmax-isotonic was comparable under isotonic and isometric conditions (human: isotonic 10 ± 4%, isometric 10 ± 4%). Moreover, a switch from isotonic to isometric conditions at Lmax-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% Lmax-isometric under isotonic conditions. Thereby, the SR was 60 ± 9% in rabbit and 51 ± 14% in human muscle strips. CONCLUSIONS: This 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.