Appraisal

Edited bv Arthur

and
C. DeGraff

reappraisal

of cardiac

therapy

and Julian Frieden

Electrophysiology
and pharmacology
of cardiac
arrhythmias.
II. Relationship
of normal and
abnormal electrical
activity
of cardiac fibers to
the genesis of arrhythmias
B. Re-entry.
Section

Andrew L. Wit, Ph.D.*

Michael R. Rosen, M.D.*
Brian F. Hoffman, M.D.
New York, A! Y.

I. The concept of re-entry

Under physiological conditions the conducting

impulse dies out after sequential activation of the
atria and ventricles because it is surrounded by
recently excited and thus refractory tissue. The
heart then must await a new impulae, normally
arising in the sinus node, for subsequent activation. The concept of re-entry implies that the propagating impulse does not conduct throughout
the heart and dies out after its complete activation but persists to re-excite the heart after the
end of the refractory period. For this to happen
the impulse must remain somewhere in the heart
while the cardiac fibers it has excited regain excitability
so that the impulse can re-enter and
reactivate them.
The effective refractory period of human cardiac fibers is long and ranges from about 150
msec. in the atrium to about 500 msec. in the
ventricular
specialized conducting 8ystem.l The
impulse destined to re-enter or re-excite the
heart therefore must survive for this period if it
is to outlast the refractory period.2 However, it
cannot remain stationary while awaiting the end
of the refractory period but must continue to conduct over a pathway which is functionally
isolated from the rest of the heart. Such a conducFrom the Department
of Pharmacology,
College of Physicians
and
Surgeons, Columbia University,
New York, N. Y. 10032.
Received for publication
June 20, 1974.
Reprint requests to: Dr. Michael R. Rosen, Department
of Pbarmacology, College of Physicians and Surgeons, 630 W. 168th St., New York,
N. Y. 10032.
*Drs. Wit and Rosen are Senior Investigators
of the New York Heart
Association.
Dr. Rosen is a Research Fellow of the John Polachek
Foundation.
Dr. Wit is a Caree? Scientist of the Irma T. Hirsch1 Trust.

664

tion pathway must provide a return route to the

regions which previously have been excited and
must be sufficiently long to permit propagation of
the impulse during the refractory period. The
cardiac impulse conducts at a velocity between
0.5 and 4 MJsec. in cardiac fibers other than
those in the sinus and atrioventricular
nodes. If it
traveled at these speeds while waiting for the remainder
of the heart to regain excitability
it
would have traveled in a pathway between 15
cm. and 1 M. long in order to survive.2 Cranefield
and Hoffman2 have stated that so long a path,
however circuitous,
could exist in functional
isolation from the rest of the heart has never
seemed likely.
Travel at a normal velocity is not the only way
in which the impulse, destined to re-enter, might
persist during the refractory period. Slowing of
the conduction velocity obviates the necessity of
such a long conduction pathway. For example, if
conduction is slowed to 0.02 MJsec., the impulse
would travel only 6 mm. during a refractory
period of 300 msec.2 Pathways of this length are
readily available in the heart. Conduction is slow
enough to enable re-entry to occur in cardiac
fibers with slow response action potentialsi.e., either in the normally
slow fibers of the
sinoatrial @A) and atrioventricular
(AV) nodes,
or in fibers whose normally
fast response has
been slowed by disease,3s 4 or other mechanisms
such as drugs.
Shortening
of the refractory period also will
facilitate the occurrence of re-entry by reducing
the period of time during which the impulse must
linger in the heart, awaiting the recovery of ex-

November,

1974, Vol. 88, No. 5, pp. 664-670