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 Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview
- 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.
Pressure volume loops
Overview:
- A graphical demonstration of how the volumes and pressures change in the LV throughout the cardiac cycle:
- Removes variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables 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.
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
As left ventricular end-diastolic pressure (LVEDP) increases owing to increased filling, stroke volume increases as well.
Image by Lecturio.
As the left ventricular (LV) volume increases during diastole, the LV pressure (LVP) generated during systole increases.
Image by Lecturio.
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 IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous 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
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:
- 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.
↓ 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:
- 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.
Frank-Starling curves and the effects of afterload on stroke volume and left ventricular end-diastolic pressure (LVEDP):
Image by Lecturio.
When afterload increases (A to B), preload increases (↑ LVEDP) but stroke volume decreases.
Pressure–volume loops illustrating the effects of afterload:
Image by Lecturio.
On the left, an increase in afterload (increased aortic pressure) requires higher pressures to be achieved during isovolumetric contraction; ultimately, this reduces stroke volume. On the right, a decreased afterload lowers the required pressure to open the aortic valve; this results in an increased stroke volume.
ESV: end-systolic volume
EDV: end-diastolic volume
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.
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
Effects of both inotropy and afterload on stroke volume
Image by Lecturio.
Pressure–volume loops illustrating the effects of inotropy:
Image by Lecturio.
On the left, as inotropy increases, so does the stroke volume, leading to a smaller end-systolic volume (ESV). On the right, as inotropy decreases, so does the stroke volume, so there is a larger volume of blood left at the end of systole.
Clinical Relevance
The following are common conditions that affect cardiac mechanics.
- Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension: condition of increased pressure in the arterial system. Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension is a state of persistently increased afterload, which puts increased strain on the heart.
- Heart failure (HF): congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure ( CHF CHF Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure) is 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 Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain, exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, and episodes of hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, dizziness, and/or syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. 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 Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the 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
Nervous system
The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system.
General Structure of the 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.
References
- 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.
- 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.
- 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.
- 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.
- Hall, J. E., Guyton, A. C. (2016). The heart. In: Guyton and Hall Textbook of Medical Physiology, 13th ed. Elsevier.
- Saladin, K.S., Miller, L. (2004). Anatomy and Physiology, 3rd ed. McGraw-Hill Education, pp. 739–740.
