Frank-Starling Relationship

Overview

Intrinsic processes within the heart exert significant control over the heart's physical pumping and operate due to basic physical features of cardiac muscle. The most important intrinsic cardiac regulatory process is the Frank-Starling Relationship which ensures that the blood volume entering the heart matches the blood volume exiting the heart across a wide range of venous return. In other words, whatever preload the heart receives from the venous return, the heart automatically pumps out. Such a phenomenon is extremely important as even a slight mismatch between blood entry and exit can cause dire consequences such as backup of blood into systemic veins, causing peripheral edema, or backup of blood into the pulmonary circulation, causing pulmonary edema.

Frank-Starling Relationship

The Frank-Starling Relationship is a physiological property of the heart described by the physiologists Otto Frank and Ernest Starling nearly a century ago. It describes the phenomenon that the stroke volume of the heart increases when the Ventricular End Diastolic Volume (VEDV), or in other words preload, increases due to additional venous return. As a result of this relationship, the Ventricular End Systolic Volume (VESV) after a heart beat is not significantly changed even when venous return and thus ventricular filling is increased (i.e. increased VEDV). The Frank-Starling Relationship can be manifested using a number of different experiments. Most simply, an isolated heart with blocked valves can be filled to different VEDV's and then electrically activated. The intraventricular pressure can be measured prior to and after stimulation of the myocardium. The data can then be plotted on something akin to a Cardiac Pressure-Volume Relationship

During passive filling of the heart in the absence of activation, the actin-myosin filaments within cardiomyocytes move apart with relative ease and thus do not generate significant pressure as the VEDV increases. However, cardiomyocytes cannot stretch indefinitely and at large VEDVs the limit of Actin-Myosin filament stretch is reached; consequently, past this limit, the passive pressure generated by the myocardium rapidly increases with even small additions of venous return. This can be observed from the "Passive Pressure" curve which initially rises little as VEDV increases but after a certain threshold begins to climb steeply.

At low levels of stretch, actin-myosin filaments are not optimally overlapped and thus do not generate their maximum possible tension upon activation. As cardiomyocytes are stretched the quantity of overlap between actin-myosin filaments increases and consequently more tension can be generated by the myocardium which translates into a higher capacity to generate active pressure during systole. However, at extremely high levels of stretch the overlap of actin-myosin filaments once again begins to fall and consequently the capacity of the myocardium to generate tension declines. This molecular mechanism explains the "Active Pressure" curve observed above in which increased VEDV initially results in higher active pressures up to a certain threshold after which the capacity of the heart to generate pressure begins to decline

For healthy individuals the quantities of VEDV the heart encounters are always within the "Physiological" Range indicated above. Consequently, when venous return and thus VEDV increase, the heart is able to generate more systolic pressure which in turn increases the stroke volume and consequently pushes out the received blood. In other words, increasing the preload of the heart enhances the heart's capacity to pump. However, in certain disease scenarios such as left heart failure, the VEDV increases to such an extent that the "Pathological" Range indicated above is reached. Here, further ventricular filling not only does not boost systolic pressures but in fact reduces them, leading to an inability of the heart to push out received blood. The pathophysiology of left heart failure is discussed further on its own page; however, an integrated understanding of the Frank-Starling Relationship forms the basis for understanding the pathogenesis of this important disease.

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