Control of Cardiac Output

1. Cardiac Output
2. Frank-Starling Law
3. Autonomic Control of the Heart
4. Autonomic Control of Vasculature
5. Baroreceptor Reflex
6. Quiz

• Cardiac output changes constantly throughout the day in order to maintain blood pressure in response to changes in total peripheral resistance, afterload and preload.
• The baroreceptors measure BP and send signals to the cardiac centre of the medulla to mediate changes in BP via the autonomic nervous system.
• The autonomic nervous system controls the heart rate, force of contraction and total peripheral resistance.

The heart must change its output (cardiac output = CO) if there is a change in total peripheral resistance (TPR) in order to maintain blood pressure (BP).

Mean arterial BP ≈ TPR x CO

For example, when metabolism in the muscles increases during exercise, blood vessels dilate to supply muscles with more blood. This causes a fall in TPR which leads to a fall in arterial pressure (as per the above equation). The heart responds by increasing the cardiac output to raise the BP.

Cardiac Output

CO = stroke volume x heart rate

The above equation shows how CO is calculated to be able to calculate mean arterial BP.

• Stroke Volume (SV) - determined by:
  • The Afterload - the blood/pressure that the ventricles pump against.
  • The Preload - the amount that the ventricles fill in diastole.
• Heart Rate (HR) - determined by:
  • The autonomic nervous system (ANS).

Frank-Starling Law

The Frank-Starling law describes how greater ventricular filling produces a stronger contraction and a larger stroke volume within the physiological range. This helps the healthy heart match its output to venous return.

The relationship between end-diastolic volume (EDV) and stroke volume (SV) depends on contractility and afterload. At a given contractile state and afterload, increasing EDV usually increases SV within the physiological range. The first figure below uses end-diastolic pressure (EDP) as an index of ventricular filling.

Diagram - How the stroke volume changes with the end diastolic pressure

SimpleMed original by Dr. Bethany Turner

Heart contractility can be altered by stimulation from the sympathetic nervous system. This causes the ventricles to pump harder, leading to an increased SV at a given EDV (as seen in the diagram above).

Filling stretches the sarcomeres before contraction. Within the physiological range, greater length increases force through length-dependent activation, including increased calcium sensitivity of the contractile proteins. A failing ventricle may gain little extra stroke volume from further filling. This impaired response should not be explained simply as actin and myosin losing contact.

Diagram - Schematic muscle length-tension relationship. Active tension can fall with excessive experimental stretch through reduced filament overlap and structural changes. This is not a ventricular stroke-volume curve or an explanation of ordinary congestion. Physiological cardiac length-dependent activation includes increased calcium sensitivity.

SimpleMed original by Dr. Bethany Turner

Autonomic Control of the Heart

The autonomic nervous system is important for many physiological functions and for control of the body systems. In the CVS it controls the heart rate, force of contraction, and peripheral resistance of blood vessels.

The parasympathetic nervous system (PNS) control of the heart is via the Vagus nerve. The Vagus has pre-ganglionic fibres which synapse with the post-ganglionic fibres on the epicardial surface, or within heart walls at the SA and AV node. The post-ganglionics release Acetylcholine (ACh) which acts on M₂-receptors causing a negative chronotropic effect (slowing of the heart rate).

• PNS causes a negative chronotropic effect by decreasing the slope of the pacemaker potential. It does this by increasing potassium ion conductance and decreasing cAMP.

The sympathetic nervous system (SNS) control of the heart is via post-ganglionic fibres from the sympathetic trunk. It innervates the SA node, AV node and myocardium. The post-ganglionics release noradrenaline (NA) which acts on β₁-adrenoreceptors, causing a positive chronotropic (the heart beats faster) and positive inotropic effect (heart beats with more force).

Sympathetic stimulation increases cyclic AMP (cAMP) in SA node cells. cAMP binds directly to hyperpolarisation-activated, cyclic nucleotide-gated (HCN) channels, which carry the mixed Na⁺/K⁺ funny current (I_f), and shifts their activation towards more positive voltages. Greater inward pacemaker current helps the cells reach threshold sooner, increasing the rate at which they fire.

cAMP also activates protein kinase A (PKA). In ventricular myocytes, this enhances calcium entry and calcium release from the sarcoplasmic reticulum, increasing the force of contraction.

Sympathetic stimulation also speeds calcium reuptake into the sarcoplasmic reticulum and ventricular relaxation. Faster relaxation helps the ventricles fill when heart rate is higher. This is a separate effect: the faster pacemaker rhythm sets heart rate, rather than faster ventricular relaxation causing the SA node to fire sooner.

Diagram - The innervation to the heart and the effects it has on the heart

Creative commons source by OpenStax College [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)] 

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