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Chapter: Modern Pharmacology with Clinical Applications: Pharmacological Management of Chronic Heart Failure

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Cardiac Electrophysiology: Refractory Period

Depolarized cardiac cells are transiently unresponsive to any activation stimuli.

Refractory Period

Depolarized cardiac cells are transiently unresponsive to any activation stimuli. During this interval, most NA+ and some Ca++ channels are inactivated, and the car-diac myocytes are said to be refractory. The refractory period is subdivided into three phases, absolute, effec-tive, and relative. The absolute refractory period is the time from the onset of the action potential until a stim-ulus is able to evoke a local nonconducted response. During this period, the cell is completely refractory to any stimulus regardless of its intensity. The effective re-fractory period (ERP) begins with the onset of the ac-tion potential, incorporates the absolute refractory pe-riod, and ends when an excitatory stimulus is able to generate a conducted signal. The ERP is determined as the shortest interval between two stimuli of equal in-tensity that results in the generation of a propagated re-sponse. The relative refractory period begins with the completion of the ERP and continues through the time in which a signal may be conducted slowly, prior to ob-taining normal propagation of the signal. Since the cell is not fully repolarized during the relative refractory pe-riod, a stronger than normal stimulus is needed to pro-duce depolarization and conduction of a propagated impulse.

Pharmacological agents that impair the function of channels normally active during phase III repolariza-tion exert their effects by prolonging the refractory pe-riod of the tissue, thereby prolonging the interval before the myocardial cells are capable of responding to a sub-sequent stimulus that will propagate in a normal man-ner. As the myocytes repolarize, they enter a relative re-fractory period during which they again can undergo depolarization. Normal conduction velocity resumes when cells are stimulated, having fully recovered at the end of the relative refractory period. Thus, the mem-brane potential at which excitation of the cell occurs de-termines conduction velocity. Conducted impulses gener-ated during the relative refractory period will propagate slowly and may contribute to the genesis of cardiac ar-rhythmias.

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