CVS - Cardiac Electrophysiology
CVS - Cardiac Electrophysiology
CVS - Cardiac Electrophysiology
Medical Physiology – MD 2
ALL SAINTS UNIVERSITY SCHOOL OF MEDICINE
DR. MARIE AFFANA
Introduction
Cardiac electrophysiology includes all of the processes involved in the electrical activation of the
heart:
- Cardiac action potentials
- Conduction of action potentials along specialized conducting tissues
- Excitability and refractory periods;
- Modulating effects of the autonomic nervous system on heart rate, conduction velocity, and
excitability; and the electrocardiogram (ECG).
Ultimately, the function of the heart is to pump blood through the vasculature. To serve as a
pump, the ventricles must be electrically activated and then contract. In cardiac muscle, electrical
activation is the cardiac action potential, which normally originates in the sinoatrial (SA) node.
The action potentials initiated in the SA node then are conducted to the entire myocardium in a
specific, timed sequence. Contraction follows, also in a specific sequence. “Sequence” is
especially critical because the atria must be activated and contract before the ventricles, and the
ventricles must contract from apex to base for efficient ejection of blood.
Origin and Spread of Excitation within the Heart
The heart consists of two kinds of muscle cells: contractile
cells and conducting cells.
The Ca2+ channels that open during the plateau are L-type
channels and are inhibited by the Ca2+ channel blockers nifedipine,
diltiazem, and verapamil.
The rule is that the pacemaker with the fastest rate of phase 4 depolarization controls
the heart rate. Normally, the SA node has the fastest rate of phase 4 depolarization,
and therefore, it sets the heart rate.
Additionally, of all myocardial cells, the SA nodal cells have the shortest action potential
duration (i.e., the shortest refractory periods). Therefore, SA nodal cells recover faster
and are ready to fire another action potential before the other cell types are ready.
Firing Rate of Sinoatrial Node and Latent Pacemakers in the Heart
Conduction Velocity
• It is the speed at which action
potentials are propagated
within the tissue.
• The units for conduction
velocity are meters per second
(m/sec).
• Conduction velocity is not the
same in all myocardial tissues:
It is slowest in the AV node
(0.01 to 0.05 m/sec) and
fastest in the Purkinje fibers (2
to 4 m/sec)
Mechanism of Propagation of Cardiac Action Potential
Action potentials at one site generate local currents at adjacent sites; the adjacent
sites are depolarized to threshold as a result of this local current flow and fire action
potentials themselves. This local current flow is the result of the inward current of the
upstroke of the action potential.
- The cable properties of the myocardial fibers. These cable properties are
determined by cell membrane resistance (Rm) and internal resistance (Ri). For
example, in myocardial tissue, Ri is particularly low because of low-resistance
connections between the cells called gap junctions. Thus, myocardial tissue is
especially well suited to fast conduction.
Excitability and Refractory Periods
In addition, there is an increase in ICa, which means there are more functional
Ca2+ channels and thus less depolarization is required to reach threshold (i.e., threshold
potential decreases).
Increasing the rate of phase 4 depolarization and decreasing the threshold potential
means that the SA node is depolarized to threshold potential more frequently and, as a
consequence, fires more action potentials per unit time (i.e., increased heart rate).
Effect of sympathetic and parasympathetic stimulation on the SA node
action potential
Negative chronotropic effects are decreases in heart rate. The most important example is
that of stimulation of the parasympathetic nervous system. Acetylcholine (ACh), released
from parasympathetic nerve fibers, activates muscarinic (M2) receptors in the SA node.
Activation of muscarinic receptors in the SA node has two effects that combine to produce a
decrease in heart rate.
First, these muscarinic receptors are coupled to a type of Gi protein called GK that inhibits
adenylyl cyclase and produces a decrease in If. A decrease in If decreases the rate of phase
4 depolarization. Second, Gk directly increases the conductance of a K+ channel called K+-
ACh and increases an outward K+ current (similar to IK1) called IK-ACh.
Enhancing this outward K+ current hyperpolarizes the maximum diastolic potential so that
the SA nodal cells are further from threshold potential. In addition, there is a decrease in
ICa, which means there are fewer functional Ca2+ channels and thus more depolarization is
required to reach threshold (i.e., threshold potential increases).
Effect of sympathetic and parasympathetic stimulation on the SA node
action potential
In sum, the parasympathetic nervous system decreases heart
rate through three effects on the SA node:
(1)slowing the rate of phase 4 depolarization,
(2)hyperpolarizing the maximum diastolic potential so that
more inward current is required to reach threshold
potential
(3)Increasing the threshold potential. As a result, the SA
node is depolarized to threshold less frequently and fires
fewer action potentials per unit time (i.e., decreased heart
rate)
Clinical Physiology: Sinus Bradycardia
DESCRIPTION OF CASE. A 72-year-old woman with hypertension is being treated with propranolol, a β-
adrenergic blocking agent. She has experienced several episodes of light-headedness and syncope (fainting).
An ECG shows sinus bradycardia: normal, regular P waves, followed by normal QRS complexes; however, the
frequency of P waves is decreased, at 45/min. The physician tapers off and eventually discontinues the
propranolol and then changes the woman’s medication to a different class of antihypertensive drugs. Upon
discontinuation of propranolol, a repeat ECG shows a normal sinus rhythm with a frequency of P waves of
80/min.
EXPLANATION OF CASE. The heart rate is given by the frequency of P waves. During treatment with
propranolol, her heart rate was only 45 beats/min. The presence of P waves on the ECG indicates that the
heart is being activated in the SA node, which is the normal pacemaker. However, the frequency of
depolarization of the SA node is much lower than normal because she is being treated with propranolol, a β-
adrenergic blocking agent. Recall that β-adrenergic agonists increase the rate of phase 4 depolarization in the
SA node by increasing If. β-Adrenergic antagonists, therefore, will decrease phase 4 depolarization and
decrease the frequency at which the SA nodal cells fire action potentials.
TREATMENT. The woman’s sinus bradycardia was an adverse effect of propranolol therapy. When propranolol
was discontinued, her heart rate returned to normal.
Autonomic Effects on Conduction Velocity in the Atrioventricular Node
The effects of the autonomic nervous system on conduction velocity are called dromotropic effects.
The most important physiologic effects of the autonomic nervous system on conduction velocity are those on the AV node,
which, in effect, alter the rate at which action potentials are conducted from the atria to the ventricles.
Stimulation of the sympathetic nervous system produces an increase in conduction velocity through the AV node
(positive dromotropic effect), which increases the rate at which action potentials are conducted from the atria to the
ventricles. The mechanism of the sympathetic effect is increased ICa, which is responsible for the upstroke of the action
potential in the AV node (as it is in the SA node). Thus, increased ICa means increased inward current and increased
conduction velocity. In a supportive role, the increased ICa shortens the ERP so that the AV nodal cells recover earlier from
inactivation and can conduct the increased firing rate.
Stimulation of the parasympathetic nervous system produces a decrease in conduction velocity through the AV node
(negative dromotropic effect), which decreases the rate at which action potentials are conducted from the atria to the
ventricles. The mechanism of the parasympathetic effect is a combination of decreased ICa (decreased inward current)
and increased IK-ACh (increased outward K+ current, which further reduces net inward current). Additionally, the ERP of AV
nodal cells is prolonged. If conduction velocity through the AV node is slowed sufficiently (e.g., by increased
parasympathetic activity or by damage to the AV node), some action potentials may not be conducted at all from the atria
to the ventricles, producing heart block. The degree of heart block may vary: In the milder forms, conduction of action
potentials from atria to ventricles is simply slowed; in more severe cases, action potentials may not be conducted to the
ventricles at all.