Page 243 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 14 Agents Used in Cardiac Arrhythmias 229

Superior
vena cava Phase 0 3
SA node 4

Atrium

AV node
Overshoot
1
0 2
Phase
0 3
mV
Purkinje 4
–100 Resting potential
Tricuspid
valve
Mitral
valve

Action potential phases
0: Upstroke Ventricle
1: Early-fast repolarization
2: Plateau R
3: Repolarization
4: Diastole
T

ECG
P
QS
PR QT
200 ms

FIGURE 14–1 Schematic representation of the heart and normal cardiac electrical activity (intracellular recordings from areas indicated
and electrocardiogram [ECG]). Sinoatrial (SA) node, atrioventricular (AV) node, and Purkinje cells display pacemaker activity (phase 4 depolariza-
tion). The ECG is the body surface manifestation of the depolarization and repolarization waves of the heart. The P wave is generated by atrial
depolarization, the QRS by ventricular muscle depolarization, and the T wave by ventricular repolarization. Thus, the PR interval is a measure of
conduction time from atrium to ventricle, and the QRS duration indicates the time required for all of the ventricular cells to be activated (ie, the
intraventricular conduction time). The QT interval reflects the duration of the ventricular action potential.

in less than 0.1 second. As a result, ventricular contraction is low and the intracellular potassium concentration high relative
synchronous and hemodynamically effective. Arrhythmias represent to their respective extracellular concentrations. Other transport
electrical activity that deviates from the above description as a result mechanisms maintain the gradients for calcium and chloride.
of an abnormality in impulse initiation and/or impulse propagation. As a result of the unequal distribution, when the membrane
becomes permeable to a given ion, that ion tends to move down
Ionic Basis of Membrane Electrical Activity its concentration gradient. However, because of its charged nature,
ion movement is also affected by differences in the electrical
The electrical excitability of cardiac cells is a function of the charge across the membrane, or the transmembrane potential.
unequal distribution of ions across the plasma membrane—chiefly The potential difference that is sufficient to offset or balance the
+
+
2+
sodium (Na ), potassium (K ), calcium (Ca ), and chloride concentration gradient of an ion is referred to the equilibrium
−
(Cl )—and the relative permeability of the membrane to each potential (E ) for that ion, and for a monovalent cation at physi-
ion
ion. The gradients are generated by transport mechanisms that ologic temperature, it can be calculated by a modified version of
move these ions across the membrane against their concentration the Nernst equation:
gradients. The most important of these transport mechanisms is
+
+
the Na /K -ATPase, or sodium pump, described in Chapter 13. It E = 61 × log C e
is responsible for keeping the intracellular sodium concentration ion C i