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(Circulation. 2000;102:IV-69.)
© 2000 American Heart Association, Inc.

Special Anniversary Issue

Regulation of Cardiac Contraction and Relaxation

Arnold M. Katz, MD; Beverly H. Lorell, MD

From the Cardiology Division (A.M.K.), Department of Medicine, University of Connecticut, Farmington, and the Cardiovascular Division (B.H.L.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.

Correspondence to Arnold M. Katz, MD, 1592 New Boston Rd, PO Box 1048, Norwich, VT 05055-1048.

Key Words: heart • contractility • inotropy • relaxation • lusitropy • calcium • heart failure

Fifty years ago, end-diastolic volume (Starling’s law of the heart) was generally believed to be the major determinant of cardiac performance. Although length-independent changes in the work of the heart had been observed by many investigators, including Starling, the significance of changing myocardial contractility was not appreciated in 1950, when Circulation was first published. Three articles published that year illustrate this lack of understanding. The first, which described patients with cor pulmonale, noted that digitalis increased the output of the failing right ventricle while right-sided filling pressures were decreased.¹ Although cardiac glycosides were concluded to improve the "function of the failing ventricle," a diagram in this article shows the failing heart operating on the descending limb of a Starling curve, with digitalis bringing the heart back to the apex of this curve. A second article examined digitalis toxicity in patients with heart failure and, citing work on isolated cardiac muscle published in the 1930s, concluded that "increased cardiac output following digitalis administration ... is presumably largely due to an enhanced contractility."² The third article described reflexes that "depress the strength of cardiac contraction," and concluded that autonomic stimulation could "modify the manifestations of Starling’s Law."³ However, because there was no foundation of knowledge that could explain "enhanced contractility," these observations could not be reconciled with the dominant view that end-diastolic volume is the key determinant of cardiac work.

Discovery of the Interplay Between Length-Dependent Changes in Cardiac Function (Starling’s "Law of the Heart") and Changing Myocardial Contractility: The "Family of Starling Curves"

The interplay between regulation by changing end-diastolic volume and changing contractility was clarified by Sarnoff,⁴ who in 1955 described the "family of . . . [Full Text of this Article]