Mechanics of the Heart

Below is a figure of a sarcomere. Ultrastructurally, thin fibers (actin) and thick fibers (myosin) interdigitate and can produce shortening of the sarcomere - The basic function of muscle.

In order to do useful shortening, the muscle will shorten against a load. In shortening, the sarcomere will develop tension. The tension is then sent out to move the load. There will be no movement of the load until tension is developed within the muscle that is adequate to move the load. If you have a 10 lb. weight in your hands, you can’t move it until you generate at least 10 lbs. of force. In the heart, the muscle is also shortening against a load, and no reduction in length occurs until that level of tension is reached.

Over-stretched muscle shows very little overlap between the thick and thin filaments. With marked shortening, there is excessive overlap. There is a range of optimal degree of shortening which gives the optimal degree of overlap (prior to activating the muscle) which would yield the most efficient tension generation. For a sarcomere, this is about 2.2 microns.

This is examined by looking at the papillary muscle which is very similar to myocardium and its properties are assumed to be representative of ventricular muscle in general. The papillary muscle is used because it is an easily worked with linear piece of muscle. A papillary muscle was attached to a load and made to shorten. A number of parameters were measured – time course of shortening, extent of shortening, and the rate of shortening (dl/dt). The generation of pressure in the heart, to move the blood out, is directly related to its ability to generate tension, and thus these characteristics are important. Muscle tension during systole (contraction) is directly related to the cardiac output about which we care – pressure to open the aortic valve and send out da blood.

So: papillary muscle tension development relates to the pressure in the ventricle and shortening of the papillary muscle relates to the reduction of size in the chamber, and therefore ejection of blood and the stroke volume.

What determines the amount of shortening? The three major determinants of muscle shortening and therefore of myocardial functioning are:

1. initial length of cardiac muscle (at onset of contraction)

2. contractility (AKA myofilament activation) – the inherent property of the muscle to be able to contract

3. afterload tension – the tension developed during contraction

These are thus the major determinants of ventricular functioning

I. Initial Length of Cardiac Muscle - PRELOAD

This is the stretch before the muscle contracts. This is end diastolic length of the muscle. This is correlated with a tension as well. Think of it as a spring. As it stretches, the elastic elements within the muscle are stretched and create a tension within the muscle. So there is an important correlation between extent of stretch and tension within the muscle fibers.

We take a piece of muscle (papillary) and you increase its length by pulling it out while plotting the tension generated. You obtain a curve like the one below which looks strikingly similar to the one from last year. This would be similar to a spring. This curve defines the properties of the muscle, and thus the diastolic ventricle, as it is being stretched.

Increasing the length of the fiber prior to contraction gives you a greater extent of contraction

This is the Frank-Starling Mechanism: Increased length leads to increased extent of shortening. When you stimulate the muscle, you first get a period of isometric contraction, depending on how much force the muscle is being asked to contract against (i.e. the load). If you take the same muscle and stretch it more and then have it contract against the same load, you see that the extent of shortening is greater. All the conditions, ultimately, result in shortening to the same point, however.

As you increase the stretch of all the ventricular fibers, you get an increased stroke volume. This is the major mechanism of increasing the stroke volume and cardiac output.

Look at the figure below, which displays some NIH data. They took strips of muscle, stretched them, froze them at that length, looked at them under the EM, and then made them contract. The X-axis shows sarcomere length, the Y-axis shows tension. The dotted line shows the passive, or diastolic, tension generated as the muscle is stretched. Notice that beyond 2.2 microns the sarcomere is very stiff, resisting further stretch so that you need a lot of force to generate a little stretch. The range between 2 and 2.2 microns seems to be an optimal range for passive stretch because at points much more than that is very difficult to stretch without an enormous increase in force. The “active tension” line represents the starling relationship. This is force developed during contraction. The range, then, between 2 and 2.2 microns seems to be an optimal range for both passive pressure and active generation of force in the sarcomere. Essentially, there is no point in stretching the muscle beyond this length because you don’t get any more force out of it.

II. Contractility

The nature of impaired contractility is incompletely understood, and the “tools of biochemistry” (i.e. first years’) are being applied to study all this. Of course, it is calcium flux that generates activation and in large part determines contractility. The calcium crosses the cell membrane, and that induces release of more calcium from the sarcoplasmic reticulum – 2 step process. This activation is referred to as contractility. It is an inherent property of the heart muscle itself and is independent of the loading factors (both pre- and after-loads).

We take a muscle fiber and stretch it out, producing some tension, and then stimulate it. You get a plot like that below. Against a given load, for a higher level of activation you get a greater degree of shortening. The graph below (still) says it much better than he did. For the same conditions of preload and afterload, the greater the contractility, the greater the degree of shortening.

Contractility can be affected by inotropes as seen below. Positive inotropes, such as norepinephrine, digitalis, glycosides, and phosphodiesterase inhibitors, increase contractility while negative inotropes such as halothane decrease contractility. Keep in mind that the preload and afterload conditions are the same.

III. Afterload

Afterload is the tension developed actively during contraction –i.e. systolic.

A series of experiments on a fiber at 2 different times can be used to examine difference which result in different afterloads – the load against which the fiber is contracting. The fibers are all preloaded the same. Here we see the relationship between the velocity of shortening of the muscle fiber and the afterload against which it is asked to contract.

Muscle contracting against a small force can do so rapidly. If the same muscle is contracting against a greater force at the upper limit of its capacity, it can do so but only slowly. (You can pick up a light load quickly whereas a heavy load can be lifted only slowly). This is an inherent property of the muscle: both the velocity and extent of shortening drops after the afterload tension increases, a point can be reached at which the velocity is zero.

If we repeat this, but bathe the fiber in Norepinepherine to increase its contractility, then we will see that for any given afterload, with the same preload, there is a greater velocity of shortening. At every point, the fiber contracts more rapidly.

For a given preload and a given level of contractility, the extent of shortening is inversely related to the afterload.

This is important therapeutically, as well. A patient’s heart that is not contracting adequately with a weak ventricle and impaired ejection fraction can improve fiber contraction (and thereby improve stroke volume and cardiac output) by reducing the afterload by decreasing peripheral resistance. Conversely, people with malignant hypertension may have heart failure because their heart may not be able to contracting against all that resistance. By dilating the vessels, you an allow the heart to contract better.

Another discussion of this can be made with reference to the pictures on page 36A (panel C) in the syllabus. These demonstrate a muscle preparation stimulated to contract against a range of afterloads. The force-velocity curve plots the afterload against the extent of shortening. The muscle develops only enough force to move the afterload, and then relaxes thereafter. It takes more and more time to develop the higher levels of tension needed to move higher and higher levels of afterload. As afterload increases both the velocity and the extent of shortening are reduced.

Look at page 36A, panels A and B. This is a set-up for an experiment that was performed. The lever at the top allows you to stretch the fiber. The dark black weight is that added prior to contraction. Again, the more added, the more the prior stretch of the muscle (preload). You can then apply the “stop” and add afterload weight. You then stimulate the muscle to contract. So you can vary both preload and afterload, and use this apparatus to measure the various characteristics of contraction. The curves in panel B show isometric contraction, then isotonic contraction, then relaxation. Panel C shows varying afterloads. Tangents to the curve show the velocity. The higher the afterload, the slower, and the less the extent, of shortening. At some point, the muscle can’t shorten at all anymore, and you see zero velocity. These are force-velocity curves.

This small print was prefaced with “I wouldn’t remember this if I were you”:

These are called force-velocity curves, and are a way of measuring contractility. One way of defining contractility is the position of this force-velocity curve. Otherwise, contractility is difficult to measure in vivo because it is hard to isolate it from the muscle’s otherwise dependence on preload and afterload. The best way to remember contractility is that it is the muscle’s ability to contract apart from these loading conditions. The curves all converge on a zero-velocity point, showing some sort of Vmax. It is felt that higher contractility would raise this Vmax.

So, how can we increase the amount of shortening?

1. Increasing the initial length of the muscle. This will increase the extent of shortening and increase stroke volume. This is increased preload – we do this when we volume expand patients with IV fluids. A typical patient would be dehydrated, with low urine output, with a reflex tachycardia

2. Increase contractility: give inotropes such as catecholamines, digitalis, phosphodiesterase inhibitors

3. Decrease afterload (reduce arterial pressure). This increases contractility due to the inverse relationship. Vasodilators are given to decrease the afterload which improves shortening of the muscle.

Category: Physiology Notes