Stretch-Induced Inotropy in Atrial and Ventricular Myocardium

Mechanical load directly regulates cardiac force. Stretching myocardial tissue results in a biphasic increase in contractility: an immediate increase (Frank-Starling mechanism) followed by a further slow increase (slow force response, SFR). Most experiments published have been performed in ventricular myocardium and very little in human tissue. We therefore highlight stretch dependent slow force responses in human myocardium and compare signal transduction in atrial and ventricular tissue. Although of comparable amplitude underlying signal transduction varies between the two tissue types. In ventricular muscle strips, the SFR is significantly reduced by inhibition of Na+/H+- (NHE) and Na+/Ca2+-exchange (NCX) but not affected by AT- and ET-receptor antagonism. In contrast, SFR in atrial tissue is neither affected by NHE- nor NCX-inhibition but interestingly, inhibition of AT-receptors or pre-incubation with angiotensin II or endothelin-1 attenuate the atrial SFR. In addition, stretch results in a large NHE-dependent [Na+]i increase in ventricle but only a small, NHE-independent [Na+]i increase in atrium. Stretch activated channels are not involved in the SFR in either tissue but contribute to basal force development in atrium but not ventricle. Thus, in human heart both atrial and ventricular myocardium exhibit a stretch-dependent SFR that is likely to serve as adjustment mechanism regulating cardiac output in case of increased preload. In ventricle on the one hand, there is a significant NHE-dependent (but angiotensin II- and endothelin-1- independent) [Na+]i increase that is translated into a [Ca2+]i and force increase via NCX. In atrium, on the other hand, there is an angiotensin II- and endothelin-dependent (but NHE- and NCX-independent) force increase. Increased myofilament Ca2+ sensitivity through MLCK-induced phosphorylation of MLC2 is contributing to the SFR in both atrium and ventricle.