Coronary perfusion and muscle lengthening increase cardiac contraction: different stretch-triggered mechanisms

An increase in coronary perfusion, transversal stretch of the myocardium, increases developed force (Fdev) (Gregg effect) through activation of stretch-activated ion channels (SACs). Lengthening of the muscle, longitudinal stretch of the myocardium, causes an immediate increase in Fdev followed by a slow Fdev increase (Anrep effect). In isometrically contracting perfused papillary muscles of Wistar rats, we investigated whether both effects were based on similar stretch-induced mechanisms by measuring Fdev and intracellular Ca2+ concentration ([Ca2+]i) after a muscle length increase from 85% to 95% L max (length at which maximal isometric force develops) at low and high coronary perfusion before and after inhibition of SACs with gadolinium (10 μmol/l Gd3+). The increase of Fdev and peak [Ca2+]i by the Gregg effect was of similar magnitude as the Anrep effect (from 3.5 ± 0.8 to 3.9 ± 1.2 mN/mm2 and from 3.0 ± 0.7% to 3.8 ± 0.9% normalized [Ca2+]i, means ± SE). SAC blockade completely blunted the increase of Fdev and peak [Ca2+]i by the Gregg effect; however, it did not affect the Anrep effect. The slow force response, but not the calcium response, was augmented by an increase in coronary perfusion. Therefore, increased coronary perfusion, transversal stretch of the myocardium, and muscle lengthening, longitudinal stretch of the myocardium, increase myocardial contraction in the rat through different stretch-triggered mechanisms.