Frank–Starling law

The Frank-Starling mechanism occurs as the result of the length-tension relationship observed in striated muscle, including for example skeletal muscles, arthropod muscle^[4] and cardiac (heart) muscle.^[5][6][7] As striated muscle is stretched, active tension is created by altering the overlap of thick and thin filaments. The greatest isometric active tension is developed when a muscle is at its optimal length. In most relaxed skeletal muscle fibers, passive elastic properties maintain the muscle fibers length near optimal, as determined usually by the fixed distance between the attachment points of tendons to the bones (or the exoskeleton of arthropods) at either end of the muscle. In contrast, the relaxed sarcomere length of cardiac muscle cells, in a resting ventricle, is lower than the optimal length for contraction.^[1] There is no bone to fix sarcomere length in the heart (of any animal) so sarcomere length is very variable and depends directly upon blood filling and thereby expanding the heart chambers. In the human heart, maximal force is generated with an initial sarcomere length of 2.2 micrometers, a length which is rarely exceeded in a normal heart. Initial lengths larger or smaller than this optimal value will decrease the force the muscle can achieve. For longer sarcomere lengths, this is the result of there being less overlap of the thin and thick filaments;^[8][9][10] for shorter sarcomere lengths, the cause is the decreased sensitivity for calcium by the myofilaments.^[11][7] An increase in filling of the ventricle increases the load experienced by each cardiac muscle cells, stretching their sarcomeres toward their optimal length.^[1]

The stretching sarcomeres augments cardiac muscle contraction by increasing the calcium sensitivity of the myofibrils,^[12] causing a greater number of actin-myosin cross-bridges to form within the muscle. Specifically, the sensitivity of troponin for binding Ca²⁺ increases and there is an increased release of Ca²⁺ from the sarcoplasmic reticulum. In addition, stretch of cardiac myocytes increases the releasability of Ca²⁺ from the internal store, the sarcoplasmic reticulum, as shown by an increase in Ca²⁺ spark rate upon axial stretch of single cardiac myocytes.^[13] Finally, there is thought to be a decrease in the spacing between thick and thin filaments, when a cardiac muscle is stretched, allowing an increased number of cross-bridges to form.^[1] The force that any single cardiac muscle cell generates is related to the sarcomere length at the time of muscle cell activation by calcium. The stretch on the individual cell, caused by ventricular filling, determines the sarcomere length of the fibres. Therefore the force (pressure) generated by the cardiac muscle fibres is related to the end-diastolic volume of the left and right ventricles as determined by complexities of the force-sarcomere length relationship.^[11][7][6]

Due to the intrinsic property of

The Frank–Starling law is named after the two physiologists, Otto Frank and Ernest Henry Starling. However, neither Frank nor Starling was the first to describe the relationship between the end-diastolic volume and the regulation of cardiac output.^[5] The first formulation of the law was theorized by the Italian physiologist Dario Maestrini, who on December 13, 1914, started the first of 19 experiments that led him to formulate the "legge del cuore" .^{[15][16][17][18][19][20][21][22][23][24][25][26][27][excessive citations]}

Otto Frank's contributions are derived from his 1895 experiments on frog hearts. In order to relate the work of the heart to skeletal muscle mechanics, Frank observed changes in diastolic pressure with varying volumes of the frog ventricle. His data was analyzed on a pressure-volume diagram, which resulted in his description of peak isovolumic pressure and its effects on ventricular volume.^[5]

Starling experimented on intact mammalian hearts, such as from dogs, to understand why variations in arterial pressure, heart rate, and temperature do not affect the relatively constant cardiac output.^[5] More than 30 years before the development of the sliding filament model of muscle contraction and the understanding of the relationship between active tension and sarcomere length, Starling hypothesized in 1914, "the mechanical energy set free in the passage from the resting to the active state is a function of the length of the fiber." Starling used a volume-pressure diagram to construct a length-tension diagram from his data. Starling's data and associated diagrams, provided evidence that the length of the muscle fibers, and resulting tension, altered the systolic pressure.^[28]

See also

• Starling equation

References