SEPTEMBER
The American
Journal
1Y 75
of CARDIOLOGY” VOLUME NUMBER
36 3
CLINICAL STUDIES
New Observations on the Effects of Atropine on the Sinoatrial and Atrioventricular
Nodes in Man
GOPAL DAS, MD, FACC FREDERICK N. TALMERS, MD, FACC ARNOLD M. WEISSLER, MD, FACC Allen Park and Detroit,
Michigan
From the Veterans Administration Hospital, Allen Park, Mich. and Wayne State University School of Medicine, Detroit. Mich. Manuscript accepted November 26, 1974. Address for reprints: Gopal Das, MD, Cardiovascular Research Laboratory, Veterans AdministrationHospital, Allen Park, Mich. 48101.
Previous observations of slowing of the heart rate after administration of atropine in doses smaller than 0.4 mg and recent reports of development of rhythm disorders in patients with acute myocardial infarction given atropine prompted us to evaluate systematically the effects of various doses of atropine (0.1 to 0.8 mg) on the response of the sinoatrial (S-A) and atrioventricular (A-V) nodes in healthy volunteers. The response of the S-A node to atropine was characteristically bimodal, slowing at smaller doses and accelerating at larger doses. In contrast, the A-V node showed acceleration of conduction in response to all doses of atropine used. A hypothesis based on current understanding of the electrophysiologic parameters governing impulse formation and impulse conduction is advanced to explain the apparent paradox in the S-A and A-V nodal responses to small doses of atropine. The results suggest the need for caution and continuous rhythm monitoring when giving atropine to patients with acute myocardial infarction.
The function of the sinoatrial (S-A) and atrioventricular (A-V) nodes is influenced by a balance between parasympathetic and sympathetic control mechanisms. Stimulation of the parasympathetic system causes a decrease in the S-A nodal rate and prolongation of A-V conduction time.’ On the other hand, blockade of parasympathetic influences results in an increase in the S-A rate and abbreviation of A-V conduction time. Previous observations have shown that atropine, an agent well known for its vagolytic action in usual doses, in fact decreases the cardiac rate in small doses.* This study was designed to evaluate the pharmacologic effects of atropine in doses ranging from 0.1 to 0.8 mg on the S-A and A-V nodes in man. Since A-V conduction is influenced by changes in heart rate as such, the effects of atropine on A-V conduction time were further studied in patients whose heart rate was maintained constant by atria1 pacing. Material
and Methods
The study was carried out in normal volunteer sub.jects aged 25 to 35 years and in patients undergoing diagnostic atria1 pacing studies. Informed consent was obtained from each person. None of the normal subjects had cardiac ab-
September
1975
The American
Journal of CARDIOLOGY
Volume
36
281
S-A AND
A-V NODAL
TABLE
RESPONSES
TO ATROPINE-DAS
ET AL.
I
Effects of Intravenous (mean + standard
Administration
of Placebo and Atropine
on S-A Nodal
Rate and A-V
Conduction
Time
error of the mean) Subjects per Group
Drug
Control
After S-A Nodal
Placebo
17
67.7
3
Drug
Change
Significance
Rate (beats/min)
1.9
67.7
1 1.9
0 + 0.7
NS
Atropine 0.1 mg
11
71.0 Jo3.8
64.8
1 3.1
-6.2
+ 1.1
/' \O.OOl
0.2 mg
14
68.1 1 2.1
62.1
1.8
-5.9
i 0.8
I'
The American
Journal
1Y 75
of CARDIOLOGY” VOLUME NUMBER
36 3
CLINICAL STUDIES
New Observations on the Effects of Atropine on the Sinoatrial and Atrioventricular
Nodes in Man
GOPAL DAS, MD, FACC FREDERICK N. TALMERS, MD, FACC ARNOLD M. WEISSLER, MD, FACC Allen Park and Detroit,
Michigan
From the Veterans Administration Hospital, Allen Park, Mich. and Wayne State University School of Medicine, Detroit. Mich. Manuscript accepted November 26, 1974. Address for reprints: Gopal Das, MD, Cardiovascular Research Laboratory, Veterans AdministrationHospital, Allen Park, Mich. 48101.
Previous observations of slowing of the heart rate after administration of atropine in doses smaller than 0.4 mg and recent reports of development of rhythm disorders in patients with acute myocardial infarction given atropine prompted us to evaluate systematically the effects of various doses of atropine (0.1 to 0.8 mg) on the response of the sinoatrial (S-A) and atrioventricular (A-V) nodes in healthy volunteers. The response of the S-A node to atropine was characteristically bimodal, slowing at smaller doses and accelerating at larger doses. In contrast, the A-V node showed acceleration of conduction in response to all doses of atropine used. A hypothesis based on current understanding of the electrophysiologic parameters governing impulse formation and impulse conduction is advanced to explain the apparent paradox in the S-A and A-V nodal responses to small doses of atropine. The results suggest the need for caution and continuous rhythm monitoring when giving atropine to patients with acute myocardial infarction.
The function of the sinoatrial (S-A) and atrioventricular (A-V) nodes is influenced by a balance between parasympathetic and sympathetic control mechanisms. Stimulation of the parasympathetic system causes a decrease in the S-A nodal rate and prolongation of A-V conduction time.’ On the other hand, blockade of parasympathetic influences results in an increase in the S-A rate and abbreviation of A-V conduction time. Previous observations have shown that atropine, an agent well known for its vagolytic action in usual doses, in fact decreases the cardiac rate in small doses.* This study was designed to evaluate the pharmacologic effects of atropine in doses ranging from 0.1 to 0.8 mg on the S-A and A-V nodes in man. Since A-V conduction is influenced by changes in heart rate as such, the effects of atropine on A-V conduction time were further studied in patients whose heart rate was maintained constant by atria1 pacing. Material
and Methods
The study was carried out in normal volunteer sub.jects aged 25 to 35 years and in patients undergoing diagnostic atria1 pacing studies. Informed consent was obtained from each person. None of the normal subjects had cardiac ab-
September
1975
The American
Journal of CARDIOLOGY
Volume
36
281
S-A AND
A-V NODAL
TABLE
RESPONSES
TO ATROPINE-DAS
ET AL.
I
Effects of Intravenous (mean + standard
Administration
of Placebo and Atropine
on S-A Nodal
Rate and A-V
Conduction
Time
error of the mean) Subjects per Group
Drug
Control
After S-A Nodal
Placebo
17
67.7
3
Drug
Change
Significance
Rate (beats/min)
1.9
67.7
1 1.9
0 + 0.7
NS
Atropine 0.1 mg
11
71.0 Jo3.8
64.8
1 3.1
-6.2
+ 1.1
/' \O.OOl
0.2 mg
14
68.1 1 2.1
62.1
1.8
-5.9
i 0.8
I'
