NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Solaro RJ. Regulation of Cardiac Contractility. San Rafael (CA): Morgan & Claypool Life Sciences; 2011.

Cover of Regulation of Cardiac Contractility

Regulation of Cardiac Contractility.

Show details

Integration of Sarcomere Mechanics with Cardiac Function Clarifies the Meaning of Preload, Afterload, and Contractility

Ultimately the properties of the sarcomeres described above are responsible for establishing and altering cardiac contractility. The data and illustrations in Figure 6 provide a means to integrate the passive and active properties of the sarcomeres into the heart beat, and to understand pre-load, afterload, and contractility. The left panel of Figure 7 schematically depicts mechanical changes of one sarcomere during a heart beat. The panels on the right show the read out of this sarcomeric activity in the form of tension and length changes at the level of a muscle strip, and in the form of pressure and volume changes at the level of the heart. The correlate of sarcomere and cellular tension is the pressure (by the Law of LaPlace), and the correlate of sarcomere and cellular length is the ventricular volume. The sarcomere schematic in Figure 7 illustrates elements, the contractile element and a spring. The spring is shown in series with the contractile element and is a lumped element representing titin, collagen, and cytoskeletal proteins. Yet in the working range of the cardiac myocytes titin is the major source of diastolic tension. Diastolic filling, represented by a load attached to the end of the sarcomere, establishes the sarcomere length before activation and this rationalizes the term “preload” as the correlate for EDV. The stretching of the passive elements as the ventricles fill in diastole gives rise to an end diastolic tension shown in the tension trace and an end diastolic pressure (EDP) shown in the ventricular pressure trace. The load the sarcomere encounters with activation is illustrated in the sarcomere in Figure 7 and termed the “afterload,” which suggests the sarcomere does not sense this load until after tension begins to develop with activation. This is roughly the course of events in the intact ventricle with afterload and rationalizes the “afterload” as the correlate of aortic pressure, which is, in essence, not sensed by the sarcomere until the aortic valve opens. With coupling of excitation to a release of Ca2+ into the myofilament space, cross-bridges are recruited into force generating cycles and the cell develops tension, shortens, and stretches the elastic element. As shown in Figure 7, when the tension matches the afterload, the sarcomere and muscle strip shortens lifting the afterload. With a constant afterload, tension develops in an isotonic twitch. In the case of the ventricle, pressure rises with no change in volume (iso-volumetric) until the valve opens and ejection commences. The ejection of the SV occurs against an increasing pressure head (afterload) as the aortic walls are stretched and recoil. Thus in the heart afterload is not constant and ejection is referred to as an auxotonic.

Figure 7. Correlates of sarcomere mechanics in ventricular function.

Figure 7

Correlates of sarcomere mechanics in ventricular function. In the muscle preparation, depicted from the perspective of a single sarcomere, a weight added to the muscle in diastole in the analogue of the EDV is a weight, the preload, added prior to activation. (more...)

With repolarization of the myocytes and re-uptake of Ca2+ by the SR, activation of the thin filament wanes and force generating cross-bridge cycling also wanes as cross-bridges detach and do not re-enter the force generating state. The cell and sarcomere return to the diastolic state ready for the next cycle. Tension is shown to fall in the isotonic twitch, and as pressure in the LV falls below the pressure in the aorta, the one-way aortic valve closes and LV pressure falls with no change in ventricular volume.

Holding the sarcomere or muscle length constant and the ventricular volume isovolumic (dashed lines in Fig. 7), provides an approach for revealing the state of contractility in the heart function shown in Figure 7. This maneuver permits isolating the contractility from changes in sarcomere length and afterload, both of which affect the number of force generating cross-bridges reacting in a force generating cycle. In this case the sarcomere and muscle strip cannot lift the load and develop the maximum isometric tension at the particular length and the ventricle develops maximum pressure at the particular constant volume (dashed lines in the right panel of Fig. 6). The approach (in animal experiments) to establishing the isovolumetric beat shown in Figure 6 is to cross-clamp the aorta making resistance and afterload infinite. This can be done reversibly to provide a snapshot of the peak pressure in an isovolumetric beat and a measure of the contractility in essentially the same way that peak tension is a measure of contractility in the sarcomere. The number of force generating cross-bridges under these conditions is thus determined by this maneuver and provides a read out by contractility. A common definition of contractility is the peak tension when the sarcomeres are neither lengthening nor shortening. As we will discuss, a useful correlate of this point in the normal beat of the heart is at the end systolic pressure at the end of ejection and as the heart enters into isovolumetric relaxation. In an isometric twitch (isovolumic beat), peak tension (peak pressure) reflects relative number of Tn sites binding Ca2+, the relative length of the sarcomeres, and the response of the myofilaments to Ca2+. As we will see these amounts of Ca2+ delivered to the myofilaments and thus the number of Tn units and cross-bridges recruited into the beat are a regulated variable in heart muscle cells. However, as we will also discuss, the response of the myofilaments to Ca2+ is also a variable affecting peak tension that must be considered in the generation of peak tension (pressure) or contractility in the isometric twitch (isovolumetric beat).

Copyright © 2011 by Morgan & Claypool Life Sciences.
Bookshelf ID: NBK54077


  • PubReader
  • Print View
  • Cite this Page

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...