Length-History Dependence of Myocardial Contraction

Wolfgang Friedrich Bluhm
Doctor of Philosophy in Bioengineering
University of California, San Diego, 1995
Professors Andrew D. McCulloch, Chair, and Wilbur Y. W. Lew, Co-Chair


The Frank-Starling mechanism describes the length-dependence of cardiac force development. In addition, myocardial contraction is length-history dependent. Active and passive forces of cardiac muscle are not uniquely determined by instantaneous muscle length but are influenced by the previous length-history. Examples include passive viscoelastic properties, such as stress relaxation, and the deactivation of active twitch force caused by rapid length changes during a contraction.

In this thesis, I studied a particularly important length-history dependent behavior of cardiac muscle. After step changes in cardiac muscle length, the immediate changes in active stress are followed by additional slow changes in stress (SCS). The mechanisms of SCS were studied in isolated left ventricular myocytes and right ventricular papillary muscles from the rabbit.

SCS accounted on average for one third of the total increase in stress with a step increase in length, with a half time of five minutes in the papillary muscles. SCS were not caused by length-history dependent changes in mechanical factors such as the more compliant muscle ends or the extracellular matrix. Therefore, SCS may be related to a length-history dependent myocardial activation.

SCS were independent of the sarcoplasmic reticulum, despite its dominant role in the activation of mammalian cardiac muscle. SCS were attenuated or reversed by a large number of positive inotropic interventions. The results suggested that SCS were most likely not caused by changes in the myofilament sensitivity to calcium but by changes in sarcolemmal ion fluxes.

A theoretical ionic model was therefore used to study individual sarcolemmal ion fluxes as potential mechanisms of SCS. SCS could be reproduced by step changes in the parameters of sarcolemmal sodium fluxes, but not by changes in calcium or potassium fluxes. In the model, SCS were mediated through primary increases in intracellular sodium concentration and secondary increases in calcium entry through the sodium-calcium exchanger.

In summary, the results of this thesis suggest that the length-history dependent phenomenon of slow changes in myocardial contraction is related to length-history dependent activation that may primarily involve stretch-induced changes in cellular sodium homeostasis.