Cardiac Mechanics

Cardiac mechanics refers to how the heart muscle pumps blood and the factors that affect
the heart's pumping function. Stroke volume (the volume of blood pumped out during each
contraction) is affected by 3 key factors: preload, afterload, and inotropy (also known as
contractility). Preload is how much the ventricle has stretched by the end of diastole (and
thus how much blood has filled the ventricles). Afterload is the pressures in the aorta that
ventricular contraction must overcome in order to open the aortic valve and eject blood into
the aorta. Inotropy is the strength of the muscle contraction itself (independent of the
preload), which is primarily related to how much intracellular Ca2+ is present.

Last updated: July 6, 2023

CONTENTS

Overview of Cardiac Output

Preload
Afterload
Inotropy
Clinical Relevance
References

Overview of Cardiac Output

Definitions
Cardiac output (CO):
Amount of blood the heart pumps per minute
CO = stroke volume x HR
Stroke volume: the amount of blood ejected during
ventricular systole
Heart rate: number of contractions per minute
CO affected by:
Preload: how much the ventricles can stretch prior to contraction
→ determines how much blood fills the ventricles (i.e.,
end-diastolic volume (EDV))
Afterload: force the ventricle needs to overcome to pump blood
out to the body (i.e., aortic pressure)
Inotropy (also called contractility): how hard the heart contracts
These factors are regulated by:
Autonomic nerves
Hormones
Frank-Starling law:
Intrinsic properties of actin and myosin filaments in the
cardiomyocytes that allow the cells to contract more the
more they are stretched.
As left ventricular end-diastolic pressure (LVEDP) increases
owing to increased ventricular filling, stroke volume
increases as well.
Preload, afterload, and inotropy are typically discussed in association
with the left ventricle (LV); however, the atria and right ventricles
respond in similar ways.
Factors in cardiac output
Image by Lecturio.

Pressure volume loops

Overview:

A graphical demonstration of how the volumes and pressures change

in the LV throughout the cardiac cycle:
Removes variable of time from the cardiac cycle graphs below
Results in a diagram appearing as a loop
X-axis: LV volume
Y-axis: LV pressure
Point A: Mitral valve opens.
Point B: Mitral valve closes.
Point C: Aortic valve opens.
Point D: Aortic valve closes.
Phases:
Ventricular filling:
Segment A → segment B
Seen as the somewhat flat line across the bottom of the graph,
moving from left to right
The volume is increasing, but because the mitral valve is open,
the increase in pressure is minimal.
Isovolumetric contraction:
Segment B → segment C
Seen as the vertical line going straight up
Mitral valve closes at B
Aortic valve does not open until C; with both valves closed, no
volume change is possible.
Ventricular contraction causes an increase in LV pressure without
a change in volume.
Ventricular ejection:
Segment C → segment D
Seen as the curved line along the top, moving from right to left
Aortic valve opens, allowing blood to leave → volume falls
Ventricles are contracting, so initially pressure increases, until
volume falls so much that pressure starts falling as well.
Isovolumetric relaxation:
Segment D → segment A
Seen as the vertical line going straight down
Aortic valve closes
Mitral valve does not open until A; with both valves closed, no
volume change is possible.
Ventricular relaxation causes a drop in LV pressure without a
change in volume.
Left ventricular pressure–volume loop:
This diagram illustrates the relationship between left intraventricular pressure and
volume throughout the cardiac cycle. The segment from point A to point B
represents ventricular filling. The mitral valve opens at A and closes at B. The
segment from point B to point C represents isovolumetric contraction. The aortic
valve opens at C. The curved line from point C to point D represents ventricular
ejection. The aortic valve closes at D. The segment from point D to point A
represents isovolumetric relaxation.
Image by Lecturio.

Preload
Preload
Definition
Preload is a measure of how much the cardiomyocytes have stretched by the end of
diastole. The Frank-Starling law is associated with preload effects on SV: ↑ preload = ↑
SV.

Length–tension relationship
The length–tension relationship explains how the Frank-Starling law works. This law
applies to striated muscle: skeletal and cardiac muscles.

The more muscle filaments (i.e., actin and myosin) are stretched apart,
the more force they can generate during contraction.
If Z bands are close together (minimal stretch at rest), there is little
room for the fibers to move closer together → weaker contraction
Therefore, the EDV is higher when:
Myocardial muscle filaments are stretched more at the end of
diastole.
Ventricular contraction is stronger.
Pressure in the ventricles during contraction is stronger.
Also known as length-dependent activation
Diagram depicting the microscopic structure of sarcomeres, actin, and myosin
Image: “The sarcomere, the region from one Z-line to the next Z-line, is the functional unit of a
skeletal muscle fiber” by OpenStax College. License: CC BY 4.0
Factors that ↑ preload
 ↑ Venous pressure → ↑ venous return → more blood returned to the
heart, which occurs with:
↓ Venous compliance (ability to stretch)
↑ Venous volume
↑ Ventricular compliance
↑ Atrial inotropy (how strongly the atria contract)
↑ Afterload: if cannot push out as much blood per stroke → ↑
end-systolic volume (ESV) → ↑ preload for the next contraction
↓ Ventricular inotropy: weaker ventricular contraction → ↑ ESV → ↑
preload for the next contraction
↓ HR: more time for the heart to fill

Effects of preload on pressure–volume loops

↑ EDV (e.g., increasing blood volume via IV fluids) = ↑ stroke volume
↓ EDV (e.g., hemorrhage) = ↓ stroke volume

Pressure–volume loops illustrating the Frank-Starling law:

On the left, increased preload from increased venous return results in a greater
EDV, which increases stroke volume. On the right, preload is reduced, and
therefore, stroke volume is reduced.
ESPVR: end-systolic pressure–volume relationship
EDV: end-diastolic volume
Image by Lecturio.
Afterload
Definition
Afterload is the resistance in the aorta that prevents blood from leaving the heart.
Afterload represents the pressure the LV needs to overcome to eject blood into the
aorta.

Effects of afterload on ventricular function

↑ Afterload:

↑ Aortic pressure→ higher pressures are required during

isovolumetric contraction to open the aortic valve:
Energy is “wasted” on isovolumetric contraction rather than on
ejection
Results in ↓ stroke volume 
↑ Preload for the next contraction
Flattens the Frank-Starling curve: ↓ rate of ventricular pressure
development
↓ Contraction velocity:
More difficult for myosin fibers to move along actin fibers →
slower shortening of sarcomeres
If you have to lift something much heavier, you will lift it more
slowly and with more difficulty.
↓ Afterload:
↓ Aortic pressure → lower pressures are required during
isovolumetric contraction to open the aortic valve
More of the contraction is used for ejection 
Results in ↑ stroke volume 
↓ Preload for the next contraction
Steepens the Frank-Starling curve: ↑ rate of ventricular pressure
development
↑ Contraction velocity:
Myosin fibers can quickly move along the actin fibers → rapid
shortening of sarcomeres
If you have to lift something light, you can do so quickly and
easily.
Inotropy
Definition
Inotropy is a measure of the force of contraction, independent of changes in preload.

Unrelated to the Frank-Starling law

Known as length-independent activation 
Ultimately controlled by levels of intracellular Ca2+:
Ca2+ allows the myofilaments actin and myosin to make contact
and move along one another.
↑ Ca2+ = ↑ strength of contraction

Factors affecting inotropy

Inotropy is increased as a result of:

Sympathetic activation:
Impulses coming from the ANS
Causes ↑ intracellular Ca2+ via:
Activation of L-type Ca2+ channels 
Release of Ca2+ from the sarcoplasmic reticulum (SR) 
Activates phospholamban: pumps additional Ca2+ back into the
SR so that the next contraction can release even more Ca2+ and
be even stronger
↑ Circulating catecholamines:
Epinephrine and norepinephrine in the blood secreted by the
adrenal medulla
Also cause ↑ intracellular Ca2+
↑ HR (Bowditch effect: the faster the heart beats, the stronger the
contractions)
↑ Afterload (Anrep effect: The heart will increase contraction strength
if it has to overcome higher afterloads.)
 Sympathetic activation increases inotropy:
Norepinephrine binding to a β-adrenergic receptor generates cAMP, which causes
the release of Ca2+ from the sarcoplasmic reticulum (SR). This provides more
intracellular Ca2+ to bind to more myofilaments, leading to a greater force of
contraction.
Image by Lecturio.

Effects of inotropy on ventricular function

↑ Inotropy:

↑ Stroke volume
Steepens the Frank-Starling curve: ↑ rate of ventricular pressure
development
Steepens the end-systolic pressure–volume relationship (ESPVR) line
on pressure–volume loops: contractions are stronger
↑ Ejection fraction
↓ Preload for next contraction
↓ Inotropy:
↓ Stroke volume
Flattens the Frank-Starling curve: ↓ rate of ventricular pressure
development
Flattens the ESPVR line on pressure–volume loops: contractions are
weaker
↓ Ejection fraction
↑ Preload for next contraction
Clinical Relevance
The following are common conditions that affect cardiac mechanics.

Hypertension: condition of increased pressure in the arterial system.

Hypertension is a state of persistently increased afterload, which puts
increased strain on the heart. 
Heart failure (HF): the inability of the heart to supply the body with
the normal CO required to meet metabolic needs. This condition may
result in chest pain, exertional dyspnea, and episodes of hypotension,
dizziness, and/or syncope. EF of the left ventricle is used to clinically
categorize HF into HF with preserved EF (≥ 50%) and HF with
reduced EF (≤ 40%), each with their own severity, prognosis, and
treatment regimens. 
Cardiomyopathies: group of myocardial diseases associated with
structural changes of the myocardium and impaired systolic and/or
diastolic function, in the absence of other heart disorders.
Cardiomyopathies can be classified as dilated, restrictive,
hypertrophic, or arrhythmogenic. With abnormal ventricular structure,
the pumping action of the ventricles can be severely impaired,
resulting in HF and/or volume overload.
Fight-or-flight response: activation of the sympathetic
nervous system (SNS), which affects several aspects of the
cardiac cycle simultaneously. Activation of the SNS increases
contractility (moving the ESPVR line up and to the left), while also
increasing venous return (↑ EDV). This results in synergistic effects,
increasing stroke volume owing to effects on both ↑ preload and ↑
inotropy.
 Pressure–volume loop, illustrating the changes that occur during the fight-or-flight
response:
The end-systolic pressure-volume relationship (ESPVR) is such that, as end-
diastolic volume increases (↑ preload) as result of sympathetic nervous system
(SNS) activation, stroke volume increases owing to the Frank-Starling law. The SNS
also increases inotropy, which also contributes to an increase in stroke volume.
Image by Lecturio.

References
1. Mohrman, D. E., Heller, L. J. (2018). Overview of the cardiovascular system. Chapter 1
of Cardiovascular Physiology, 9th ed. McGraw-Hill Education. Retrieved from
https://accessmedicine.mhmedical.com/content.aspx?aid=1153946098. 
2. Mohrman, D. E., Heller, L. J. (2018). Vascular control. Chapter 7 of Cardiovascular
Physiology, 9th ed. McGraw-Hill Education. Retrieved from
https://accessmedicine.mhmedical.com/content.aspx?aid=1153946722. 
3. Mohrman, D. E., Heller, L. J. (2018). Regulation of arterial pressure. Chapter 9 of
Cardiovascular Physiology, 9th ed. McGraw-Hill Education. Retrieved from
https://accessmedicine.mhmedical.com/content.aspx?aid=1153946898. 
4. Baumann, B. M. (2016). Systemic hypertension. Chapter 57 of Tintinalli, J.E., et al.
(Eds.), Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8th ed.
McGraw-Hill Education. Retrieved from
https://accessmedicine.mhmedical.com/content.aspx?aid=1121496251. 
5. Hall, J. E., Guyton, A. C. (2016). The heart. In: Guyton and Hall Textbook of Medical
Physiology, 13th ed. Elsevier.
6. Saladin, K.S., Miller, L. (2004). Anatomy and Physiology, 3rd ed. McGraw-Hill
Education, pp. 739–740.