Isometric force depends on resting muscle length preload
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B. C. Isometric force depends on resting muscle length (preload). As in skeletal muscle the force of contraction is very dependent on the geometry of the overlap between the thick and thin filaments. Isometric force depends on resting muscle length (preload).

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Isometric force depends on resting muscle length preload

B

C

Isometric force depends onresting muscle length (preload).

As in skeletal muscle the force of contraction is very dependent on the geometry of the overlap between the thick and thin filaments


Isometric force depends on resting muscle length preload

Isometric force depends onresting muscle length (preload).

Starling’s law of the heart: The more the heart is filled during diastole the more forcefully it will contract during systole


Isometric force depends on resting muscle length preload

The top figure is actually for skeletal muscle because the relaxed tension is still zero at the peak of the contracted curve (Lo). Contrast that to the curve in in the lower panel.

The high passive tension opposes over-filling of the ventricle during diastole.


Isometric force depends on resting muscle length preload

A change in contractility is defined as a change in force of contraction not related to a change in length.

A change in contractility can be seen as a shift in the “contracted” curve either up (an increased contractility) or down (a decreased contractility)


Isometric force depends on resting muscle length preload

  • Hearts never find themselves beyond Lo due to:

  • Passive force

  • Pericardial restraint

  • Fiber slippage (dilation)


Isometric force depends on resting muscle length preload

Sympatheic nerve activity is the usual cause of an increased contractility.

Heart failure occurs when contractility is pathologically reduced

Contractility is hard to measure in patients


Isometric force depends on resting muscle length preload

Isotonic contraction is where the tension is held constant and the muscle is allowed to shorten

The greater the load the slower it shortens

If the length is increased at any load the speed of shortening increases

The force-velocity curve can be extrapolated to zero force to determine the maximum velocity of shortening,Vmax. Notice that Vmax is the same at all lengths


Isometric force depends on resting muscle length preload

Vmax should be a length-independent index of contractility.

Edmund Sonnenblick

Changes in contractility shift the entire curve including the y axis intercept, Vmax


Isometric force depends on resting muscle length preload

The heart actually contracts in an isotonic manner

A tetanized skeletal muscle would contract to here

Aortic pressure

3. At this point the ventriclebegins to eject and the contraction becomes isotonic

125

100

2. Isometric

contraction as

pressure builds

75

stroke

Pressure (mmHg)

1. The ventricle is filled

volume

50

25

20

40

60

80

100

Volume (ml)


Isometric force depends on resting muscle length preload

Otto Frank in 1895 appreciated that and tried to use the analysis below to calculate stoke volume of a frog heart.

Unfortunately the frog heart starts to relax before the ejection is complete

Aortic pressure

3. At this point the ventriclebegins to eject and the contraction becomes isotonic

125

100

2. Isometric

contraction as

pressure builds

75

stroke

Pressure (mmHg)

volume

1. The ventricle is passively filled

50

25

20

40

60

80

100

Volume (ml)


Isometric force depends on resting muscle length preload

In the 1970s Kiichi Sagawa found that, due to their plateaued action potential, canine and human hearts stay activated long enough to reach equilibrium during ejection.

4. Contraction

Aortic pressure

3. At this point the ventriclebegins to eject and the contraction becomes isotonic

stops here

125

100

2. Isometric

contraction as

pressure builds

75

stroke

Pressure (mmHg)

1. The ventricle is filled

volume

50

25

20

40

60

80

100

Volume (ml)


Isometric force depends on resting muscle length preload

The ejection loop


Isometric force depends on resting muscle length preload

Changing filling pressure changes stroke volume only by changing LVEDV

This could be an example of transfusion

Lowering LVEDP has the opposite effect


Isometric force depends on resting muscle length preload

Lowering the aortic pressure causes the ventricle to empty more completely.

The stroke volume increases by an amount equal to the fall in LVESV.

LVEDV is not affected.

This is part of the rationale for afterload lowering therapy

Raising aortic pressure has the opposite effect


Isometric force depends on resting muscle length preload

Increasing contractility decreases LVESV and thus increases stroke volume.

LVEDV is not affected.

Heart failure has the opposite effect


Isometric force depends on resting muscle length preload

  • There are only three ways that the body can alter stroke volume from minute-to-minute:

  • Filling pressure (preload)

  • Aortic pressure (afterload)

  • Contractility


Isometric force depends on resting muscle length preload

Actually the heart beat is Auxotonic

i.e the load changes during shortening

For our analysis isotonic is a close approximation


Isometric force depends on resting muscle length preload

Decreasing the diastolic compliance decreases LVEDV and stroke volume but has no effect on LVESV

Decreased compliance is a serious compli-cation for hearts with concentric hypertrophy


Isometric force depends on resting muscle length preload

Decreases diastolic compliance

Pressure overload causes concentric hypertrophy where the ventricle remodels inwardly to a low lumen volume and a thick wall.

Caused by hypertension or outflow track obstruction.


Isometric force depends on resting muscle length preload

Caused byregurgitant aortic valve or AV fistulas.

Volume overload leads to eccentric hypertrophy.

The heart remodels outwardly to give a large lumen diameter but a near normal wall thickness.

Increases diastolic compliance


Isometric force depends on resting muscle length preload

  • Changes in compliance occur only in disease and are not a physiological regulator

  • Wall thickening or thinning

  • Delayed or incomplete relaxation


Isometric force depends on resting muscle length preload

How can we measure contractility in a heart?


Isometric force depends on resting muscle length preload

1960’s

Sarnoff’s ventricular function curve.


Isometric force depends on resting muscle length preload

Three factors control the stroke volume: filling pressure, aortic pressure and contractility.

So how can we control for the former two?


Isometric force depends on resting muscle length preload

By plotting the stroke work against filling pressure any change in filling pressure is accounted for.


Isometric force depends on resting muscle length preload

Using stroke work instead of stroke volume corrects for changes in aortic pressure.


Isometric force depends on resting muscle length preload

Notice that stroke volume and aortic pressure change in a reciprocal manner.

Stroke Work = AOP x SV

As AOP goes up SV naturally goes down so their product remains relatively constant.

Stroke work should be independent of any change in blood pressure.


Isometric force depends on resting muscle length preload

Changes in contractility change stroke volume.

Changes in aortic pressure also change stroke volume.

Since aortic pressure changes reciprocally with aortic pressure their product (stroke work) is independent of aortic pressure


Isometric force depends on resting muscle length preload

Disadvantages of the cardiac performance curve method

1. Highly invasive

2. Cannot make comparisons between patients (not a useful clinical test)


Isometric force depends on resting muscle length preload

How can we measure contractility in the patient?

Ejection fraction = (LVEDV-LVESV) / LVEDV

The fraction of the ventricular contents at end diastole that is ejected.


Isometric force depends on resting muscle length preload

How can we measure contractility in the patient?

Ejection fraction = (LVEDV-LVESV) / LVEDV

  • Can be easily measured But….

  • Affected by contractility

  • Affected by preload

  • Affected by afterload

  • Affected by compliance


Isometric force depends on resting muscle length preload

Thus, dP/dt of the ventricular pressure increases with contractility

Changes in contractility shift the entire force-velocity curve.

At any afterload increasing contractility increases velocity of shortening.


Isometric force depends on resting muscle length preload

Unfortunately, preload also affects dP/dt


Isometric force depends on resting muscle length preload

Vmax

The maximum velocity of shortening Vmax as calculated from the force velocity curve is independent of length and a good index of contractility.

Vmax in an intact heart can be estimated from the ventricular pressure with:

dP/dt.

P


Isometric force depends on resting muscle length preload

Vmax

Unfortunately, Vmax seems to measure the contractility of the best muscle in the heart and is a poor index in regional dysfunction.


Isometric force depends on resting muscle length preload

The heart appears to vary its elasticity from very elastic in diastole to very stiff in systole.

slope =Emax

Pressure

Elasticity = ΔV/ΔP

Stiffness = Δ P /ΔV

Volume

Vo


Isometric force depends on resting muscle length preload

The maximum stiffness Emax occurs during systole.

Emax and Vo (volume at zero pressure) describe the ventricle.

slope =Emax

Pressure

Volume

Vo


Isometric force depends on resting muscle length preload

A device called the conductance catheter allows instantaneous measurement of ventricular volume and pressure so that an ejection loop can be viewed in real time in a patient.

By varying aortic pressure several end-systolic pressure-volume points can be measured.


Isometric force depends on resting muscle length preload

By fitting a straight line to the ESPVR, Emax and Vo cal be calculated


Isometric force depends on resting muscle length preload

The area within the ejection loop is proportional to the mechanical work done by the heart (external work).


Isometric force depends on resting muscle length preload

The external work correlates poorly with the oxygen consumption (metabolic energy) of the heart.


Isometric force depends on resting muscle length preload

If the triangle to the left of the ejection loop is added to the area of the ejection loop, the correlation with oxygen consumption on a per beat basis is almost perfect.

It can be shown that the triangle correlates with internal work during the isovolumetric phase of contraction.


Isometric force depends on resting muscle length preload

Increased blood pressure may cause less external work but will always increase oxygen consumption.

Elevated blood pressure puts a high metabolic load on the heart.


Isometric force depends on resting muscle length preload

Decreasing blood pressure will always decrease oxygen consumption.


Isometric force depends on resting muscle length preload

A patient receives a drug that increases aortic pressure and decreases end diastolic pressure. What did the drug do?


Isometric force depends on resting muscle length preload

Why do nitrates relieve angina?


Isometric force depends on resting muscle length preload

What are the pros and cons of the ejection fraction as an estimate of contractility?


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