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(Circulation. 2001;104:1585.)
© 2001 American Heart Association, Inc.

Editorial

Titin

An Elastic Link Between Length and Active Force Production in Myocardium

John L. Sutko, PhD; Nelson G. Publicover, PhD; Richard L. Moss, PhD

From the Departments of Pharmacology (J.L.S.) and Physiology and Cell Biology (N.G.P.) and the Graduate Program in Biomedical Engineering (N.G.P.), University of Nevada School of Medicine, Reno; and the Department of Physiology (R.L.M.), University of Wisconsin School of Medicine, Madison.

Correspondence to John Sutko, Department of Pharmacology/318, University of Nevada-Reno, Reno, NV 89557. E-mail sutko@unr.edu

Key Words: Editorials • heart failure • myocardium

Studies by Frank, Starling, and colleagues demonstrated that elevations of end-diastolic volume increase cardiac output in working hearts,¹ a phenomenon referred to as the Frank-Starling (FS) relationship. It stands as one of earliest descriptions of the importance of diastolic dimensions to systolic function, yet how alterations in sarcomere length (SL) influence myofilament Ca²⁺ sensitivity, and hence the inotropic state of the heart, is not completely understood. The FS relationship in the intact ventricle is qualitatively similar to the underlying length-tension relationship in single cells. As length is increased from short SLs (1.7 µm), the force developed by a myocardial cell increases to a peak at an SL of 2.3 µm, corresponding to the maximum SL in working hearts. Similarly, when end-diastolic volume is increased, cardiac work during systole also increases. It is clear, however, that the FS relationship in cardiac muscle cannot be explained as straightforwardly as the length-tension relationship in skeletal muscle, ie, based solely on changes in overlap of the thick and thin filaments. In skinned myocardium, the length-tension relationship obtained during maximal activation with Ca²⁺ looks very much like that seen in maximally activated skeletal muscle. At submaximal concentrations of Ca²⁺, however, the relationship becomes much steeper, so that force increases rapidly as SL is increased from 1.7 to 2.3 µm. Thus, the steepness of the FS relationship appears to be a predictable consequence of submaximal levels of Ca²⁺ activation during a typical cardiac twitch. Consistent with this interpretation, there is compelling evidence that length-dependent . . . [Full Text of this Article]

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