Human atrial skinned muscle fibers exhibit reduced length-dependent activation but show faster force development kinetics than ventricular muscle.

In humans, the left atria (LA) and the left ventricle (LV) play distinct physiological roles and express sarcomeric proteins with chamber-specific patterns. Despite these important differences, most multi-chamber descriptions of the heart assume uniform myocardial properties. To facilitate a more accurate representation of cardiac function, we measured and compared the contractile properties of isolated skinned human LA and LV muscle fibers at 37 °C. Our experimental measurements included the length-dependent activation (LDA) of force in the isometric steady state, the force response to small quick length changes, and tension redevelopment dynamics. The LV measurements display more pronounced LDA behavior compared to LA, whereas the LA dynamics is generally faster than LV. To elucidate these differences mechanistically, we used the LA and LV experimental datasets to fit a biophysical model framework to produce a representative model for each chamber. Our Bayesian statistical approach aimed to maximize the objectivity of the model calibrations and to allow a systematic assessment of chamber-specific parameter differences. Passive mechanical properties emerge as the principal determinant of LDA behavior. However, variations in cross-bridge cycling kinetics account more significantly for LA/LV differences in the ATP consumption to produce a given isometric force. These results constitute the first systematic biophysical comparison of LA and LV cardiomyocyte contraction mechanics in humans, paving the way to further investigation of their roles within the broader cardiovascular physiological context.