The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca 2+ ions at a longer sarcomere length, commonly referred to as myofilament length dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the "Frank-Starling law of the heart" constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development. KeywordsFrank-Starling Law of The Heart; Length-Tension Relationship; Sarcomere length; Regulation Frank-Starling's Law of the HeartOver a century ago, Otto Frank in Germany and Ernest Starling in England reported on the relationship between the extent of ventricular filling and pump function of the heart, a phenomenon collectively referred to as Frank-Starling's Law of the Heart. A modern view of this phenomenon [1] (illustrated in Figure 1) holds that there is a unique relationship between end-systolic volume and end-systolic pressure in the heart that is solely determined by contractile state. As a consequence, for a given contractile state, ventricular stroke volume is i) proportional to diastolic filling (i.e. preload), and ii) stroke volume can be maintained in the face of increased aortic pressures (i.e. afterload) simply by increasing preload as illustrated by the two pressure-volume loops in Figure 1. Contractile state, within this framework, can be viewed as any factor that alters end-systolic pressure independently of end-systolic volume and Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Figure 1). The ESPVR-slope is a very useful index of cardiac contractility that can be measured in situ by various methods; a convenient and popular approach is the use of the pressure-volume conductance catheter [2]. The cellular mechanisms that underlie the ESPVR are discussed in the following section. NIH Public Access Relationship between whole heart property and myofilament length dependent activationPump function of the heart is intimately related to force generation, active shortening, and regulation of card...

Background: Myocardial infarction (MI) leads to proteolytic cleavage of cMyBP-C (hC0C1f) and decreased contractility.Results: hC0C1f can incorporate into the human cardiac sarcomere, depressing force generation and increasing tension cost.Conclusion: Interaction between hC0C1f and both actin and α-tropomyosin causes disruption of intact cMyBP-C function.Significance: Proteolytic cleavage of cMyBP-C is sufficient to cause contractile dysfunction following MI.

This study shows that exercise performed at a late stage after MI restored a transmural non-uniformity of myocardium lost during HF. Recoveries of Ca(2+) homeostasis and myofilament function of cardiomyocytes contribute to this beneficial effect.