Download JAOK HAN, MD, PH.D.

430
LETTERS TO THE EDITOR
decreasing the arterial pressure and coronary blood
flow.
JAOK HAN, M.D., PH.D.
Department of Medicine
Albany Medical College
Albany, New York
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References
1. EPSTEIN SE, REDWOOD DR, SMITH ER: Atropine and
acute myocardial infarction. Circulation 45: 1273,
1972
2. HAN J, DETRAGLIA J, MILLET D, MOE GK: Incidence
of ectopic beats as a function of basic rate in the
ventricle. Amer Heart J 72: 632, 1966
3. HAN J: Mechanisms of ventricular arrhythmias associated with myocardial infarction, Amer J Cardiol
24: 800, 1969
4. SCHERLAG BJ, HELFANT RH, HAFr JI, DAMATO AN:
Electrophysiology underlying ventricular arrhythmias
due to coronary ligation. Amer J Physiol 219: 1665,
1970
5. HAN J, GOEL BG, HANSON CS: Re-entrant beats
induced in the ventricle during coronary occlusion.
Amer Heart J 80: 778, 1970
6. HAN J: The concepts of reentrant activity responsible
for ectopic rhythms. Amer J Cardiol 28: 253, 1971
7. HAN J: Ventricular ectopic activity in myocardial
infarction. In Cardiac Arrhythmias, edited by Han J.
Springfield, Illinois, Charles C Thomas, 1972, p 171
8. HAN J: Ventricular vulnerability during acute coronary
occlusion. Amer J Cardiol 24: 857, 1969
9. KENT KM, SMITH ER, REDWOOD DR, EPSTEIN SE: The
deleterious electrophysiologic effects produced by
increasing heart rate during experimental coronary
occlusion. (Abstr) Clin Res 20: 379, 1972
10. LOWN B, KLEIN MD, HERSHBERG PI: Coronary and
precoronary care. Amer J Med 46: 705, 1969
The authors reply:
To the Editor:
We appreciate the opportunity of responding to some
of the questions raised by Dr. Han in his letter. Dr.
Han makes a very important point when he emphasizes
that his own observations (demonstrating that slower
heart rates during experimental acute myocardial
infarction increase the incidence of ventricular premature beats) were made mainly within the first 1-3 min of
onset of acute coronary occlusion.' We certainly do not
question the importance of these results, given this time
frame and the fact that open-chest anesthetized dogs
were used with the attendant increase in circulating
catecholamines, faster control heart rates, etc. However,
it is questionable how relevant the data are to the
problem we were mainly concerned with; i.e., the
advisability of giving atropine to the patient with
bradycardia and acute myocardial infarction. In this
circumstance, practical considerations make it virtually
impossible for any therapeutic intervention to be
applied for the first few minutes after onset of
infarction. It therefore seems to us that this important
clinical question relates not so much to the first 3 min of
the onset of myocardial infarction but to the effects of
increasing heart rate on the incidence of ventricular
premature contractions and ventricular fibrillation over
the course of the first 1-3 hours after onset of acute
infarction.
Dr. Han is not entirely accurate in suggesting that
the time course of onset of ventricular arrhythmias after
coronary occlusion between his and Dr. Scherlag's
studies1' 2 was very different. Moreover, although
interpretation of Dr. Scherlag's paper is complicated
when evaluating the results following the very fastpaced heart rates, Dr. Han neglects to mention another
phase of the study in which these investigators reported
that ventricular slowing produced by vagal stimulation
caused disappearance of ventricular ectopic beats in all
instances. Nevertheless, interpretative difficulties do
remain since this study was not specifically designed to
answer the question we were interested in exploring.
We therefore investigated the effects of atropine (using
a randomized study design) on ventricular arrhythmias
over the first few hours of acute coronary occlusion in
the closed-chest conscious dog.3 This model was chosen
so that the relative arrhythmic potential of a physiologic
range of heart rate could be evaluated. We found that
the incidence of serious ventricular arrhythmias was
directly related to the spontaneous heart rate; i.e.,
slower heart rates (< 60 beats/min) were accompanied
by a lower incidence of ventricular ectopic activity and
ventricular fibrillation. Moreover, we found that when
compared to a saline-treated control group the
incidence of ventricular arrhythmias and ventricular
fibrillation was higher in dogs whose baseline heart
rates were increased from a mean of 88-107 beats/min
by an infusion of atropine.
A second aspect of the problem raised in Dr. Han's
letter is the influence of heart rate on electrophysiologic
parameters that may influence the incidence of
ventricular arrhythmias. Dr. Han and his co-workers
demonstrated that both ischemia and bradyeardia
independently increase the disparity of the length of
ventricular refractory periods (thereby favoring development of reentrant arrhythmias) and decrease ventricular fibrillation threshold.4 While we do not question
these experimental results, we do wonder whether some
of the conclusions derived from these results are entirely
valid. For example, several authors have interpreted
these data as supporting the hypothesis that increasing
the heart rate of a patient with an acute myocardial
infarction who has bradyeardia will diminish the risk of
arrhythmic death. Although this may be true, it
appeared somewhat tenuous to us to extrapolate data
obtained in the absence of ischemia to the ischemic
situation since, to our knowledge, Dr. Han has never
published studies showing that a slower heart rate
during acute myocardial infarction leads to deleterious
electrophysiologic effects (with the exception of a figure5
illustrating temporal dispersion data obtained from
only a single dog).
Our own skepticism originated from the finding that
increasing heart rate, even from rates as slow as
30-40/min, increased the degree of ischemic injury in
the closed-chest conscious dog,6 a result which
suggested to us that altering heart rate might have very
different electrophysiologic effects in the presence of
ischemia. When this hypothesis was tested, we indeed
Circuiation, Volume XLVII, February 1973
LETTERS TO THE EDITOR
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found that the results in the absence of ischemia were
opposite to those found during ischemia. Thus,
increasing heart rate during ischemia increased the
dispersion of recovery of refractory periods and
decreased fibrillation threshold.7 More recently, we
demonstrated that when heart rate was increased from
50-60 to 90 beats/min by lowering the intensity of vagal
stimulation, ventricular fibrillation threshold during
ischemia consistently decreased; the mean decrease was
37%.8 In addition, over this same heart rate range,
disparity of recovery of refractory periods increased in
half of the animals tested. Thus, our results clearly
indicate that during acute coronary occlusion in the
dog, increasing heart rate within a range similar to that
present during acute myocardial infarction in man
causes electrophysiologic effects that would favor
development of reentrant arrhythmias and increase the
heart's vulnerability to ventricular fibrillation.
We would certainly agree with Dr. Han that atropine
and cardiac pacing have a definite place in the
management of bradyeardia in the setting of a coronary
care unit, but would add the proviso that these
interventions are clearly indicated only when severe
bradycardia is complicated by excessive hypotension or
excessive ventricular ectopic activity. The point we wish
to emphasize is that we do not know the precise
definitions of "severe" or "excessive," nor what the
limits of safety are when heart rate is increased, since
our own studies would indicate that relatively modest
increases in heart rate may produce deleterious effects.
Nor do we know whether increasing modest levels of
hypotension by increasing heart rate is truly beneficial.
For example, although hypotension has been shown
experimentally to increase the degree of ischemic injury
produced by coronary occlusion,6 9 patients with acute
myocardial infarction observed in a coronary care unit
who had hypotension unassociated with clinical
evidence of vasoconstriction or impaired regional
perfusion were reported not to have a significantly
higher mortality than patients without hypotension.10 It
therefore is not clear whether under these circumstances the net effect on ischemic injury of modest increases in pressure at the expense of an increased heart
rate diminishes or augments the degree of ischemic
injury.
In conclusion, our own orientation toward this very
important question is that the role of atropine in the
treatment of bradyeardia in acute myocardial infarction
is uncertain, insofar as the specific situations in which
atropine may result in a net beneficial effect; and those
in which it may result in a net deleterious effect still
must be defined.
STEPHEN E. EPsTEIN, M.D.
DAVID R. REDWOOD, M.B., M.R.C.P.
Cardiology Branch
National Heart and Lung Institute
Bethesda, Maryland
ELDON R. SMITH, M.D.
Department of Medicine
Victoria General Hospital
Halifax, Nova Scotia
Circulation, Volume XLVII, February 1973
431
References
1. HAN J, DETRAGLIA J, MILLET D, MOE GK: Incidence
of ectopic beats as a function of basic rate in the
ventricle. Amer Heart J 72: 632, 1966
2. SCHERLAG BJ, HELFANT RH, HAFT JI, DAMATO AN:
Electrophysiology underlying ventricular arrhythmias
due to coronary ligation. Amer J Physiol 219: 1665,
1970
3. KARSH RB, ORLANDO M, NORMAN D, EPSTEIN SE:
Ineffectiveness of prophylactic atropine in decreasing
arrhythmias and enhancing survival following acute
coronary artery occlusion in conscious dogs. (Abstr)
Amer J Cardiol 29: 273, 1972
4. HAN J, MILLET D, CHIZZONITTI B, MOE GK: Temporal
dispersion of recovery of excitability in atrium and
ventricle as a function of heart rate. Amer Heart J
71: 481, 1966
5. HAN J: The concepts of reentrant activity responsible
for ectopic rhythms. Amer J Cardiol 28: 253, 1971
6. REDWOOD DR, SMiTH ER, EPSTEIN SE: Coronary
artery occlusion in the conscious dog: Effects of
alterations in heart rate and arterial pressure on the
degree of myocardial ischemia. Circulation 46: 323,
1972
7. KENT KM, SMITH ER, REDWOOD DR, EPSTEIN SE: The
deleterious electrophysiologic effects produced by
increasing heart rate during experimental coronary
occlusion. (Abstr) Clin Res 20: 379, 1972
8. KENT KM, SMITH ER, REDWOOD DR, EPSTEIN SE:
Electrical stability of acutely ischemic myocardium:
Influences of heart rate and vagal stimulation. Circulation 47: 291, 1973
9. MAROKO PR, KjEKCSHUs JK, SOBEL BE, WATANABE T,
COVELL JW, Ross J JR, BRAUNWALD E: Factors
influencing infarct size following experimental coronary artery occlusions. Circulation 43: 67, 1971
10. LOWN B, VASSAUX C, HooD WB JR, FAKHRO AM,
KAPLINSKY E, ROBERGE C: Unresolved problems in
coronary care. Amer J Cardiol 20: 494, 1967
Echocardiographic Pattern of Right
Ventricular Diastolic Volume
Overload in Children
To the Editor:
This article (CIRCULATION 46: 36, 1972) is quite
good and does confirm previous observations having
been made by echocardiography. I would like to
comment on the three cases of right ventricular volume
overload that had normal septal motion by echocardiography. Two of these are illustrated in the article.
Case 13 was illustrated as having normal septal motion
and is a case of anomalous pulmonary venous
connection. The echocardiogram illustrated is taken
from low in the left ventricle near the apex, and there is
no evidence of the mitral valve being present. Past
experience with scanning technics involving a strip chart
recorder rather than Polaroid films has shown that in
people with atrial septal defects with abnormal septal
motion as you scan near the apex you tend to get a
normal septal motion. I feel strongly that in order to
make the diagnosis of abnormal septal motion you must
Atropine and Acute Myocardial Infarction: The authors reply:
STEPHEN E. EPSTEIN, DAVID R. REDWOOD and ELDON R. SMITH
Circulation. 1973;47:430-431
doi: 10.1161/01.CIR.47.2.430
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