Download Acute Hemodynamic Effects of Hexa

Acute Hemodynamic Effects of Hexamethonium in Normotensive Man
By Louis
RAKITA,
M.D.,
AND SALVATORE
M.
ASSISTANCE OF GLADYS HECKMAN, R.N.,
SANCETTA,
M.D.,
WITH THE TECHNICAL
AND HANNA JANOUSKOVEC,
R.X.
The effect of intravenous hexamethonium bromide was studied in 10 normotensive human subjects in the steady state. In the absence of over-all change in cardiac output, the variable decrease
in arterial pressure is accounted for by decrease in calculated total peripheral resistance.
in Douglas bags (four minutes), and the oxygen
content obtained by passage through the Pauling
oxygen analyzer. All volumes were corrected to
standard temperature and pressure. The maximal
difference allowed between two successive oxygen
consumption and cardiac output check determinations was 10 per cent (steady state).
Following basal determinations, hexamethonium
was administered intravenously at a rate of 1 mg.
per minute for 10 minutes; dosage and rate of administration were grossly doubled thereafter until a
noticeable decrease in brachial arterial pressure was
observed. In three patients receiving a total of 120
nig., the last 50 mg. were injected at a rate of 10
mg. per minute. The total dosage varied from 15 to
120 mg. Basal studies were repeated 30 minutes
following termination of injection.
The following changes from the basal during the
experimental period were considered significant: (a)
20 per cent for mean brachial artery pressure, (b)
more than 10 per cent for cardiac index, (c) more
than 15 beats per minute for heart rate, (d) 5 mm.
Hg for pulmonary artery pressure, and (e) 20 per
cent for calculated resistances and left ventricular
work.
Complete data are presented in 10 of 12 patients;
the other six were eliminated from the documentation because of failure to maintain a steady state or
poor blood analysis checks.
T
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
HE INCREASING clinical use of
hexamethonium, a ganglion blocking
agent, makes desirable a detailed knowledge of its acute hemodynamic effects in
normotensive man. Recent work on dogs 1 ' 2
indicates that the hexamethonium-induced fall
in arterial pressure is accompanied by significant decrease in cardiac output with increase in the calculated total peripheral resistance. Accordingly, the authors concluded that
the decrease in arterial pressure was due to
the reduction in the cardiac output. Such
findings require confirmation in humans. The
present investigation was designed to serve
this purpose.
MATERIAL AND METHODS
Eighteen normal subjects free of cardiac or pulmonary disease, infection or fever were selected from
the medical wards. Following light sedation, routine
dextrocardiao catheterization was performed in an
ambient temperature of 24 C. Central venous pressures transduced via Statham strain gages, and
brachial arterial pressures, measured through an
indwelling arterial needle, were simultaneously inscribed with an electrocardiogram on a Brush sixchannel oscillograph. Mean pressures were derived
by planimetries integration of two consecutive respiratory cycles. Left ventricular work as well as total
peripheral and pulmonary resistance was calculated
by conventional formulas.
All blood specimens were withdrawn in duplicate
and oxygen contents were determined spectrophotometrically.3 The maximal variation allowed between
checks was ±0.2 volumes per cent. Expired air,
measured through a dry gas test meter, was collected
RESULTS AND DISCUSSION
Pertinent data are presented in table 1.
1. Brachial artery pressure tended to decrease in all patients except D. B. In the latter,
a larger dose might have been effective, since
there was great variation in dosage-response.
2. Pulmonary artery pressure tended to decrease in nine subjects; there was an insignificant rise in three subjects.
3. The cardiac index increased in three, decreased in three, and was unaltered in four
individuals. The average change for the entire
group was +0.8 per cent.
From the Department of Medicine, Western Reserve University at City Hospital, Cleveland, Ohio.
This investigation was supported by a grant (No.
H-13S2) from the National Heart Institute of the
U. S. Public Health Service.
Received for publication June 4, 1953.
499
Circulation Research, Volume I, November 1953
500
EFFECTS OF HEXAMETHONIUM IN MAN
4. Tlcart rate rose in all subjects except one
(L. B.) in whom an insignificant fall was noted.
5. Total peripheral resistance decreased in
noted in II. G., and was dissociated from the
changes in T.P.R. and cardiac index.
7. Left ventricular work was reduced in nine
TABLE 1.—Hemodynamic Effects of Hexamethonium Bromide in Normotensive Humans
Pt.
Hex. mg.
OJCM'
us
C.I.
H.R.
P A .P.
T.P.R.
Pu.AR.
L.V.W.
71
88
+ 17
17/5
(10.8)
16/5
( 9.5)
- 1 2 % •- ( 1.3)
1750
11S5
-32.3%
ISO
144
-22.0%
6.42
5.55
-12.0%
14/8
(10.7)
8/3
( 5.0)
—17.0% - ( 5.1)
1572
1372
-12.7%
226
147
-35.0%
3.79
2.06
—15.6%
(102)
138/81
(78)
107/71
-23.5% - ( 3 4 )
+6.7%
2.73
3.10
+ 13.5%
B.
Ex.
96/59
( 74)
62/45
( 52)
—30.6% - ( 22)
102
93
-8.8%
2.21
1.75
—20. S%
73
88
+ 15
L. A.
M-48
1.65 M"
50 B.
Ex.
105/53
( 76)
80/44
(59)
-22.0% - (17)
130
136
+4-6%
3.51
3.19
-9.1%
73
79
+0
F. P.
M—30
1.68 M1
70
90/60
( 73)
77/4S
( 59)
-19.0% - ( 14)
128
13S
3.60
4.27
+ 18.6%
J. 11.
M—29
1.78 M«
70
A. C.
M-25
1.87 M«
120
E. II.
F-26
1.71 M'
70
8. II. G.
M—49
1.87 M>
58
9. L. B.
F— 53
1.80 M1
15
B.
Ex.
D. B.
F-34
1.62 M !
65
B.
Ex.
11.* C. T.
M—28
1.81 M'
120
12.' D . V.
M—23
1.79 M 1
120
W. J.
M-37
1.69 M»
70
2. A. R.
M—39
1.69 MJ
20
1.
3.
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
4.
5.
0.
7.
10.
Average percentile change
B.
Ex.
B.A.P.
B.
Ex.
B.
Ex.
B.
Ex.
B.
Ex.
B.
Ex.
B.
Ex.
B.
Ex.
126
+7.8%
+2.0% + ( 0.3)
106S
920
-13.1%
+ 12.1%
5.84
4.14
-29.0%
73
109
+36
18/5
(11.0)
15/5
( 9.0)
—18.1% - ( 2.0)
960
654
-31.8%
148
99
-32.4%
6.15
5.69
-7-4%
3.51
4.22
+20.2%
55
94
+ 39
22/14
(17.0)
14/8
(11.0)
- 3 5 . 3 % - ( 6.0)
9S0
690
-29.6%
3.12
3.42
S3
97
+ 14
18/10
(14.0)
14/7
(10.0)
-28.5% -(4.0)
975
7S6
-19.3%
83
103
12/5
( 7.8)
11/6
( 7.3)
-6.4% -(0.5)
950
879
-7.4%
+2.5%
5.04
3.80
—22.6%
993
825
—16.8%
173
203
+ 17.3%
5.65
3.55
-37.3%
24/8
23/7
(14.9)
(15.2)
209
234
( 74)
1OS/51
90/51
( 65)
-12.9% - ( 9)
+2.2%
91/63
( 71)
S9/57
( 64)
-10.9% - ( 7)
126
130
+3.1%
87/51
( 67)
66/45
( 56)
-16.2% - ( 11)
114
118
+3.5%
3.27
2.96
-9.4%
89/59
( 72)
66/48
( 52)
-28.4% - ( 20)
139
133
-4.3%
3.10
2.70
-12.9%
+9
(12.6)
(12.8)
+ 1.5% + ( 0.2)
120/63
( 92)
72/46
( 58)
-37.0% - ( 34)
126
119
-5.5%
3.21
3.07
-4.3%
79
74
—5
23/12
(15.6)
19/12
(13.1)
—16.0% —( 2.5)
1232
812
-34.0%
208
181
—12.8%
7.44
4.47
-38.4%
1.77
1.60
-10.0%
63
88
+25
20/10
(13.2)
12/7
( 7.7)
- 4 1 . 6 % - ( 5.5)
2038
2264
+ 11.0%
368
240
-34.7%
2.80
2.50
-10.7%
75
83
(11.4)
(11.7)
+2.6% + ( 0.3)
-17.0%
—20.9%
-20.5%
92/59
90/62
0%
( 73)
( 74)
+( 0
135
138
81
85
+7.8%
+9.6%
106/60
( 76)
Sl/51
( 58)
- 2 3 . 6 % - ( 18)
91
100
17/8
21/S
73
90
-46.3%
6.50
+3.1%
186
130
-30.0%
5.63
5.50
-24.0%
112
115
19/7
(11.4)
13/8
(10.0)
- 1 2 . 3 % - ( 1.4)
+ 17
+0.8%
6.30
us
17/8
16/9
+8
111/66
( 79)
90/5S
( 71)
- 9 . 8 % - ( 8)
—20 3 %
+20
220
+ 19.1%
—17. 3 %
!
Key: B.: basal, Ex.: experimental, B.A.P.: mean brachial arterial pressure, O2CM : oxygen consumption in cc./sq. meter/min.. C.I.: cardiac
index in liters/niin., H . R . : heart rate, P.A.P.: pulmonary arterial pressure (mean pressures in parentheses), T.P.R.: total peripheral resistance,
Pu.A.R.: pulmonary artery resistance (dynes/sec./cm." 6 ), L.V.W.: left ventricular work (Kg. meters/min.)
* Not included in averages.
all patients except one (D. B.) in whom a
negligible increase occurred.
0 Total pulmonary artery resistance decreased in seven subjects; two showed a negligible rise. A slight and unexplained rise was
patients; a negligible increase due to a significant rise in cardiac index was noted in J. H.
Basal peripheral arterial oxygen saturation
values (range: 94 to 96.5 per cent) were unchanged. The form of the electrocardiograms^
LOUIS RAKITA AND SALVATORE M. SANCETTA
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
was unaltered except for changes produced by
variations in heart rate.
The data demonstrate that there is no direct
relationship between the changes in cardiac
index and those that occur in the arterial blood
pressure. Rather, there is a tendency for pulmonary and peripheral arterial pressures, pulmonary and total peripheral resistances, and
the mechanical work of the left ventricle to
decrease. The differences between these findings and those in anesthetized normotensive
and renal hypertensive dogs 1 ' 2 is emphasized
by subjects W. J., F. P., J. H. in which
definite decreases in arterial pressure were
attended by increases in the cardiac index and
reductions in calculated resistance. In other
cases (A. R., E. H., L. B.), despite a decrease
in the cardiac index, calculated resistance still
was lowered. On the average, the cardiac index
underwent no change, whereas the other
modalities measured showed borderline significant percentile alterations.
The action of hexamethonium in man appears to differ from that reported in dogs. The
conclusion germane to the dog data, that decrease in cardiac output is responsible for fall
in arterial pressure does not apply to man.
With dosage at times greater than that administered to dogs, hexamethonium in man
produced a fall in peripheral arterial pressure
purely as a result of ganglion blockade, with
variable changes in the cardiac output. The
varying degree of tachycardia usually encountered altered the total output changes.
Our findings corroborate the undocumented
report of Freis and associates.4
There is much Individual variability in
dose-response. Had our object been to produce
a standard fall in blood pressure, greater reductions might have resulted. From the standpoint of caution, we ceased administration of
501
the drug pursuant to a noticeable decrease in
peripheral arterial pressure, and did not feel
justified in continued administration in the
face of a definite tachycardia.
SUMMARY AND CONCLUSIONS
1. Hexamethonium bromide was administered intravenously to 12 normotensive individuals in a steady state. Complete data are
presented for 10 of these subjects.
2. Changes in cardiac output are variable,
and the heart rate is generally increased.
Brachial and pulmonary artery pressure, and
calculated total peripheral and pulmonary
resistances, and left ventricular work undergo
an over-all decrease. There is marked individual
variation in dose-response.
3. These data indicate that hexamethonium
lowers arterial pressure in normotensive man
primarily by diminishing total peripheral resistance, rather than by diminishing cardiac
output.
REFERENCES
1
MURPHY, Q. R., O'BRIEN, G. S., RENNIE, D. W.,
CAPPS, R. T., ROWE, G. G., ANTD CRUMPTON,
C. W.: Effect of hexamethonium bromide (C-6)
on cardiovascular system in normotensive and
hypertensive dogs. Fed. Proc. 12: 101, (March),
1953.
2
CRUMPTON, C. W., ROWE, G. G., CAPPS, R. T.,
O'BRIEN, G. S., AND MURPHY, Q. R.: Effect of
hexamethonium bromide on coronary flow,
cardiac work and cardiac efficiency. Proc, Nat.
Meet. Am. Fed. Clin. Res. No. 25, (May 3),
1953.
3
HICKAM, J. B., AND FRAYSEH, R.: Spectrophotometric determination of blood oxygen. J. Biol.
Chem. 180: 457, 1949.
* FREIS, E. D., ROSE, J. C, HIGGINS, T. F., KELLEY,
R. T., SCHNAPER, H . W., AND JOHNSON, R. L.:
The hemodynamic effects of hexamethonium in
man. J. Clin. Investigation 31: 029, 1952 (Abstract) .
Acute Hemodynamic Effects of Hexamethonium in Normotensive Man
LOUIS RAKITA, SALVATORE M. SANCETTA, HECKMAN R.N. GLADYS and
JANOUSKOVEC, R.Y. HANNA
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
Circ Res. 1953;1:499-501
doi: 10.1161/01.RES.1.6.499
Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1953 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7330. Online ISSN: 1524-4571
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circres.ahajournals.org/content/1/6/499
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the
Editorial Office. Once the online version of the published article for which permission is being requested is
located, click Request Permissions in the middle column of the Web page under Services. Further information
about this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation Research is online at:
http://circres.ahajournals.org//subscriptions/