Frank-Starling law of the heart

Overview
The Frank-Starling law of the heart (also known as Starling's law or the Frank-Starling mechanism) states that the more the ventricle is filled with blood during diastole (end-diastolic volume), the greater the volume of ejected blood will be during the resulting systolic contraction (stroke volume). This relationship holds up to a certain volume, but past that volume, there is a decline in contractility. This decline in contractility is referred to as "falling of the Starling curve". This is the mechanism by which the left ventricle initial dilates and increases contractility to adopt to chronic aortic insufficiency, but then eventually fails as it becomes to large and "falls off the Starling curve".

Historical Perspective
The law is named after the two physiologists, Otto Frank and Ernest Starling who first described it.

Long before the development of the sliding filament hypothesis and our understanding that active tension depends on the sarcomere's length, in 1914 Ernest Starling hypothesized that "the mechanical energy set free in the passage from the resting to the active state is a function of the length of the fiber." Therefore, the initial length of myocardial fibers determines the work done during the cardiac cycle.

Pathophysiology
The force of contraction increases as the heart is filled with more blood. This is a direct consequence of increasing the load on a single muscle fiber. In particular, such increased load stretches further the myocardium and enhances the affinity of troponin C for calcium, hence increasing the contractile force. The force that any single muscle fibre generates is proportional to the initial sarcomere length (known as preload), and the stretch on the individual fibres is related to the end-diastolic volume of the ventricle. In the human heart, the maximal force is generated with an initial sarcomere length of 2.2 micrometers, a length which is rarely exceeded in the normal heart. Initial lengths larger or smaller than this optimal value will drop the force of the muscle owing to: less overlap of the thin and thick filaments for larger values and more overlap of the thin filaments for smaller values.

Premature Ventricular Contractions
This can be seen most dramatically in the case of a premature ventricular contraction. The premature ventricular contraction causes early emptying of the left ventricle (LV) into the aorta. Since the next ventricular contraction will come at its regular time, the filling time for the LV increases, causing an increased LV end diastolic volume. Because of the Frank-Starling law, the next ventricular contraction will be more forceful, causing the ejection of the larger than normal volume of blood, and bringing the LV end-systolic volume back to baseline.

Chronic Aortic Insufficiency
This is the mechanism by which the left ventricle initial dilates and increases contractility to adopt to chronic aortic insufficiency, but then eventually fails as it becomes to large and "falls off the Starling curve". While left ventricular dilation is associated with increased cardiac output according to the Frank-Starling mechanism, at a certain point of left ventricular dilation, the left ventricle begins to fail as left ventricular contractility falls. At this point, the left ventricular ejection fraction falls. The left ventricular end systolic volume begins to rise. Next the left ventricular end diastolic volume begins to rise and this causes dyspnea or frank pulmonary edema. The first symptoms of the rise in left ventricular end diastolic pressure may be an increase in dyspnea on exertion.