Clinical Physiology Heart Function

Eran Kalmanovich, 2004

Cellular and molecular factors of pathological cardiac excitability

The resting membrane potential potential of an individual cardiac
muscle is about -90 mV, which is very much close to the K+
membrane potential. The efflux of K+ polarize the membrane and
any changes in the external K+ concentration affect the resting
membrane potential of cardiac muscle. The normal range of the plasma K+ is 3.5-4.5 mmol/liter.
1. Hyperkalemia when extracellular K+>7.5 mmol/L. This
may lead to depolarization of the cell membrane, which lead
to asystole. The long lasting depolarization will cause
inactivation of the fast Na+ channels (involved in the fast
raising phase of the AP). Some changes can be recorded on
ECG.
2. Hypokalemia when the extracellular K+<2.7 mmol/L. It
doesnt produce hyperpolarization, due to the behavior of
the K+ channels, which will become close. But it will cause
prolonged repolarization, unstable resting potentialmm it
will increase ectopic activity, and increase the risk for
ventricular ES, tachycardia and fibrillation.

Ionic currents and membrane potential changes

The range of the of physiologic membrane potential
is between -100 mV (K+) to 60 mV (Na+).
For potassium always outward current
For sodium always an inward current
For calcium only inward
For chloride have both outward and inward
currents (cause depolarization of the cell).

Clinical Physiology Heart Function

Eran Kalmanovich, 2004

Basic arrythmogenic mechanisms

There are three basic mechanisms causing arrhythemias
1. Automaticity ectopic activity. Sometimes silent areas become active.
2. Re-entry reexcitation of a region of cardiac tissue by single impulse, continuing for one or
more cycles and sometimes resulting in ectopic beats or tachyarrhythmias. It can exist over
either anatomical or a functional area of slowed impulse
conduction and requires also refractoriness of tissue to
stimulation an area of unidirectional block to conduction
a. Anatomical reenter in which the block to
conduction is an anatomical obstacle. Described by
the ring model
b. Anisotropic -reentry that is functional in not
occurring around an anatomical obstacle but whose
functional properties are conferred by inherent
structural anisotropy of the cardiac muscle fibers.
Thus it has qualities of both functional and
anatomical reentry.
c. Atrial reentry in which the entire reentrant circuit
lies within one or both atria, excluding the sinus
node
d. Functional reentry in which the block to
conduction is due to functional heterogeneity of the
electrophysiological properties of region of cardiac
tissue, it is usually described by the leading circle models
e. Sinus nodal reentry in which impulses tracers a reentrant circuit within or near the
sinus node before being conducted to the rest of the heart.
3. After potential both cases are cause intracellular Ca, when myocardial cell are Ca-overload,
there maybe spontaneous leakage of Ca from SR. it might cause a development of new AP.
a. Early early after depolarization (EAD)
i. New AP develops before reaching the RMP
ii. Long action potential
iii. Long QT a predisposition
iv. Drugs
v. Low K+
vi. Related to Torsado de potintes (a ventricular tachycardia)
vii. EAD can result in malignant type of ventricular premature contraction.
b. Late delayed after depolarization (DAD)
i. Transient inward current is present
ii. Excess Ca2+
iii. catecholamines
iv. Digitalis toxin.
Long QT syndromes
Long action potential with channel-pathies in the background.
1. LQT1,2 K-channel disorders. The K+ currents are decreased so theres no repolarization and
the AP are prolongs.
2. LQT3 the Na-channels is mutated, there is an increase Na+ current (inward) and a greater
chance to develop EAD
2

Clinical Physiology Heart Function

Eran Kalmanovich, 2004

Interacellular concentration of Ca+ - dependent arrhythmogenic mechanisms

Myocardial infract
most patients with MI and heart failure die from arrhythmias. The local extracellular level K+ in the infracted
area is elevated and higher than in the living tissue and it can reach to up to 40 mmol/L.

Heart failure
The cardiac pump function is insufficient to maintain circulation.
In later staged of heart failure, the myocardium is remodeled. Also
the sympathetic activity is high, there is an activation of the betaadrenergic which cause an increase of the cAMP intracelullary
which than result in increase in the intracellular levels of Ca2+
can lead to DAD. Other factor like rennin-angiotensin system and
the left ventricular dilation may lead eventually to ventricular
tachycardia and fibrillation.

Anti arrhythmic drugs

The slow conduction in the conduction system and
myocardium, doing so they depress ectopic activity
and reduce discrepancy between normal and reentrant
paths so that reentry doesnt occur.
The drug classification:
1. Class 1 Na+ channels (fast) blockers
2. Class 2 beta-adrenegic receptors blockers
3. class 3 K+ channel blockers (prolong
refractory period of cardiac muscle)
4. Class 4 L-type Ca+2 channels blockers.
Sometimes these drugs can have proarrhythmic effects
on patients.