2. Cardiovascular adaptation in health and disease

Page created on September 29, 2018. Last updated on December 12, 2019 at 22:16


During exercise the body requires more blood per second than in rest, meaning that the cardiac output to the muscles must increase. In healthy people, this is done with several mechanisms:

  • The myocardial contractility increases
  • The heart rate increases
  • The preload increases
  • The afterload decreases
  • Cardiac output is redistributed from visceral organs to the muscles

Circulating catecholamines and increased sympathetic activity is responsible for the first three. Vasodilation of the vessels in the muscles cause the total peripheral resistance and therefore the afterload to decrease.

People with heart failure cannot increase the cardiac output during exercise by these mechanisms. These people rely on very increased heart rate to increase CO, but that is not sufficient. They have high sympathetic tone, which increases the TPR, hampering the CO.


These notes assume you know most of the cardiac physiology from physiology. For repetition:

Preload = the extent to which the myocardium is stretched at the end of diastole, right before systole. Preload depends on the end-diastolic volume (EDV), which mostly depends on venous return to the heart.

Afterload = the force that the ventricles must eject blood against during systole. Afterload depends mostly on the pressure in the aorta, measured by the mean arterial pressure (MAP), and the total peripheral resistance (TPR).

Stroke volume (SV) = the volume of blood ejected by the heart in systole. It’s defined like this: SV = EDV – ESV

Ejection fraction (EF) = the fraction of blood that was inside the ventricle before systole that got ejected in systole. EF = SV / EDV

Cardiac output (CO) is determined by the following formula:

Cardiac output = stroke volume x heart rate

The arterial blood pressure is determined by the following formula:

Arterial blood pressure = Cardiac output x total peripheral resistance

Frank-Starling mechanism

The Frank-Starling mechanism or law is a mechanism that is built into the heart. The mechanism adjusts stroke volume according to the venous return in order to maintain cardiac output. The result is that the cardiac output of both the left and the right ventricles remain the same.

The mechanism works like this: When venous return increases, the preload increases, which stretches the ventricles more. The ventricles respond to this increased stretch by increasing the force of contraction. This causes the stroke volume to increase. We can imagine the cardiac muscle like a spring or rubber band: the more it’s stretched, the harder it will snap back!

The result is that the when more blood enters the heart, more blood is ejected, so the amount of blood coming into the heart is always constant with the amount going out of it.

When the body needs more blood, during exercise

The cardiac output is 5 L/min in rest. In some cases, the body’s need for blood exceeds these 5 L/min. The best example for increased need for blood is in exercise, but it also increases when the temperature around a person is high. In healthy people, the cardiac output in exercise increases to 20-25 L/min, or even up to 40 L/min in athletes! The heart accomplishes this by multiple mechanisms:

  • Increasing the stroke volume
    • Increasing the contractility of the myocardium
    • Increased preload
    • Decreasing afterload
  • Increasing the heart rate

Increasing the heart rate and stroke volume directly increase the cardiac output, as they’re the two determinants of the CO. Stroke volume can be increased by three mechanisms, which we will see later.

These mechanisms are activated during exercise by the sympathetic nervous system, circulating catecholamines and local vasodilators in muscles. The SNS will release norepinephrine into β1-receptors in the myocardium, increasing the contractility and the heart rate. Circulating catecholamines will vasoconstrict veins, returning more blood to the heart. Local vasodilators will vasodilate vessels in the muscles, decreasing the total peripheral resistance and therefore the afterload.

Increasing heart rate

An increase in heart rate cause a direct increase in cardiac output. This increase comes from sympathetic activation and circulating catecholamines.

Increasing the heart rate is effective in increasing the cardiac output, but only up to a certain limit. The increase in heart rate is mediated by increased sympathetic tone and circulating catecholamines. However, the downside with this is that the coronary blood flow is reduced. This is because the coronary arteries are compressed during systole, so blood only flows in those arteries during diastole. When heart rate increases, the diastolic time decreases, so that the cardiac muscle has less time to be perfused. This is made even worse by the fact that when heart rate increases, the oxygen demand of the myocardium increases as well. This means that tachycardia by itself only allows increased cardiac output up to a certain level, and the heart needs other mechanisms as well.

Increased stroke volume:

Stroke volume is increased by three factors:

  • Increased preload
  • Increased myocardial contractility
  • Decreased afterload

Recall that most of the blood in the body is stored in the veins. When catecholamines are released during exercise, these veins will vasoconstrict so that they will stop “storing” the blood and instead push it into the circulation. This causes more blood to return to the heart, i.e. the preload increases. By the Frank-Starling mechanism this causes the myocardial contractility and therefore the CO to increase as well.

Sympathetic activation will release norepinephrine into local β1-receptors in the myocardium, yielding a positive inotropic effect, meaning that the myocardial contractility increases. When the contractility increases the ejection fraction increases, meaning that less blood remains in the ventricles after systole. During rest the ejection fraction is around 65%, meaning that, of the 110 mL of blood in the ventricles before systole, only 70 mL is ejected during each systole. When the contractility increases the ejection fraction increases to 75 – 80%, so approx. 80 mL are ejected.

Lastly, a decreased afterload will increase the stroke volume. During sympathetic activation all arterioles in the circulation will be strongly vasoconstricted, which would increase the total peripheral resistance. However, during exercise local vasodilators in the muscles will overcome this vasoconstriction, causing the arterioles in the active muscles to be vasodilated. This vasodilation is so great that the total peripheral resistance decreases. This decreases the afterload of the heart, which increases the stroke volume.

The total peripheral resistance decreases during exercise, yet the blood pressure increases. Recall that the blood pressure is determined by the cardiac output as well as the TPR. During exercise the TPR decreases, but the cardiac output more, so there is a net increase in blood pressure. Mainly the systolic pressure is increased; the diastolic doesn’t increase much. The unchanged diastolic pressure shows how the afterload is kept low.

It’s important for the ventricles to have a high compliance (be distensible). When the compliance is sufficiently high, as in healthy people, the ventricles can fill with blood without increasing the pressure inside the ventricles, called end-diastolic pressure (EDp). When this pressure is low blood will easily flow from the large veins into the ventricles, but if the EDp is high will this flow will be impaired.

Redistribution of cardiac output during exercise

Another important factor in exercise is the redistribution of blood from non-essential organs to the muscles and to the skin. Organs like the kidneys and the GI tract will receive much less blood, but the skin, coronaries and skeletal muscle will receive much more. This occurs due to the selective vasoconstriction of visceral arterioles, while arterioles of the muscles are vasodilated.

At rest


During moderate exercise

1300 mL

GI tract, liver

600 mL

1100 mL


550 mL

400 mL


1700 mL

700 mL


700 mL

200 mL


550 mL

750 mL

Striated muscle

8000 mL

550 mL

Bones, others

450 mL

5000 mL


12 500 mL

Note how the brain perfusion is kept constant. The body will always try to maintain brain perfusion. The coronary and cerebral circulations are not highly innervated by the sympathetic nervous system, so the arterioles of those circulation will not be vasoconstricted. Hence, their perfusion is unaffected by sympathetic activation.

Cardiac output in disease

See the next topic for an explanation of how the cardiac output changes in heart failure.


The way the circulation adapts to an increased CO demand, such as what happens in physical exercise, is very different between healthy people and people with heart failure. The differences are summed up below:


Healthy people

Heart patients

Resting heart rate

Around 60-70

Around 90

Dominant autonomic tone in rest

Parasympathetic tone dominates

Sympathetic tone dominates

Reserve in heart rate

Large. Can increase from 60 -> 200

Small. Can only increase from 90 -> 150

Contractility during exercise

Increases. EF increases.

Can’t increase due to myocardial injury. EF low.

How fast does HR increase during exercise?



Left ventricular compliance

Good. EDp doesn’t increase when EDV increases.

Bad. EDp increases when EDV increases.

Change in afterload

Decreases due to vasodilation in muscle

Increases due to high sympathetic tone

Increase in BP

Only systolic BP increases

Both systolic and diastolic BP increases

How quickly HR normalizes after exercise

Normalizes quickly

Normalizes slowly

Fitness level

The Rock

Danny Devito

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