Potentiation and intrinsic regulations in mammalian heart muscle

Repeated paired stimuli (S1–S2) were applied to isolated atrial and ventricular preparations. Isometric force and transmembrane action potentials were recorded at different S1–S2 intervals. At the intervals where S2 evokes an action potential, developed force gradually attains a higher level during the S1–S2 train. This mechanical behavior is quantitatively dependent on the timing of S2. Potentiation is graded during the electrical relative refractory period and related to the amplitude of the premature electrical response. This relationship was confirmed under conditions of massive response, where propagation was suppressed and the whole muscle was activated at once. Potentiation can be augmented by interposing multiple (premature) action potentials between driven beats. By increasing the S1–S2 interval the premature contraction becomes evident and increases while the first one (driven) decreases. Mechanical events are delayed one cycle after the electrical ones. Three factors are proposed to account for the intrinsic inotropic regulation: a potentiating factor related to the action potential; an ionic compartment; and a restitution factor.