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(Circulation Research. 2002;90:11.)
© 2002 American Heart Association, Inc.

Editorials

Frank-Starling Relationship

Long on Importance, Short on Mechanism

Richard L. Moss, Daniel P. Fitzsimons

From the Department of Physiology and the Cardiovascular Research Center, University of Wisconsin Medical School, Madison, Wis.

Correspondence to Richard Moss, Dept of Physiology, 1300 University Ave, Madison, WI 53706. E-mail RLMoss@physiology.wisc.edu

Key Words: myocardium • Frank-Starlingrelationship • Ca²⁺ sensitivity

The Frank-Starling relationship is an intrinsic property of myocardium by which increased length (or ventricular volume) results in enhanced performance during the subsequent contraction.^1–3 This relationship appears to be very important in cardiac function because increased venous return and the corresponding increase in end-diastolic volume result in greater stroke volume during the next beat. The ventricles can thus accommodate increased venous return by means of a more vigorous contraction that ejects the greater volume of blood from the heart.

Although the physiological significance of the Frank-Starling relationship is widely appreciated, its cellular basis is not well understood. One hypothesis is that more cross-bridges interact with actin at longer sarcomere lengths due to length-dependent reductions in lateral spacing between thick and thin filaments,^3–5 ie, due to closer proximity to actin more crossbridges bind and thereby increase contractile force (see Figure). Measurements in permeabilized myocardium held at constant length have shown that osmotic compression increases force at each [Ca²⁺]. Thus, the greater Ca²⁺ sensitivity of force at long lengths can be achieved at short lengths by reducing fiber diameter. Moreover, osmotic compression actually eliminates the length dependence of Ca²⁺ sensitivity.⁴ This evidence suggests that lateral filament spacing is a primary determinant of the Frank-Starling relationship, but the evidence is incomplete because studies to date have only measured muscle diameter and not the actual spacing between thick and thin filaments. Diameter and filament separation are likely to increase or decrease in concert, but these changes need not be proportionate because the . . . [Full Text of this Article]

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