Hemodynamic Effects of Lidocaine in

Patients with Heart Disease

By RICHARD R. SCHUMACHER, M.D., ALAN D. LIEBERSON, M.D.,
RICHARD H. CHILDRESS, M.D., AND JoHN F. WILLIAMS, JR., M.D.

SUMMARY
The intravenous administration of 50 mgof lidocaine as a single bolus to four
patients with heart disease did not result insignificant change in cardiac output or
a
left ventricular end-diastolic pressure (LVEDP). Two patients had moderate decrease
in systemic arterial pressure which was not accompanied by symptoms, was of short
duration, and did not require therapeutic intervention. Left ventricular function, as
assessed by the relationship of changes in stroke volume index (SVI) and stroke work
index (SWI) to changes in LVEDP, was not significantly affected nor was the maximum
rate of rise of left ventricular pressure (dp/dt).
The intravenous injection of 100 mg of lidocaine into eight additional patients
with heart disease did not produce a statistically significant change in any of these
hemodynamic variables when compared to their respective control values. Examination
of individual responses, however, revealed that some depression of left ventricular func-
tion occurred in at least three and probably four of these patients. Nevertheless, this
depression of myocardial function was not of sufficient magnitude to produce symptoms
or reduce the cardiac output and generally did not result in an inordinate increase in
LVEDP.
It is concluded that 100 mg or less of lidocaine injected intravenously has remarkably
few, if any, adverse hemodynamic effects of clinical significance in man.
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Additional Indexing Words:

Cardiac output Ventricular functi Systemic arterial pressure

T HE DEVELOPMENT of cardiac ar- quinidine and procainamide, two of the more

rhythmias in patients with heart disease
occurs all too frequently and the serious con-
sequences which may result are well known
to all clinicians. Although several drugs are
available which can abolish many of these
arrhythmias, enthusiasm for their administra-
tion often is tempered by knowledge of the
undesirable hemodynamic effects which they
are capable of producing. The propensity for
From the Medical Service, Veterans Administra-
tion Hospital, and the Department of Medicine,
Indiana University School of Medicine, Indianapolis,
Indiana.
This work was supported in part with the facilities
provided by Research Grant HE-06308 from the
National Heart Institute, U. S. Public Health Service,
Postgraduate Cardiovascular Research Training
Grant HTS-5363 from the National Heart Institute,
and the Indiana Heart Association.
commonly used anti-arrhythmic agents, to
produce systemic hypotension when admin-
istered intravenously is well known, and a
depressant effect upon the myocardium has
been observed by several investigators.' 4 The
discovery that diphenylhydantoin also was
effective in abolishing many cardiac arrhyth-
mias and that significant systemic hypotension
did not occur with intravenous administration
appeared to offer promise that this was a
more ideal anti-arrhythmic agent for intra-
venous use than either quinidine or procain-
amide. However, recently it has been demon-
strated that diphenylhydantoin also is not
totally devoid of adverse hemodynamic effects
since it will depress myocardial function in
patients with heart disease.5 Furthermore,
fatalities have occurred after its intravenous
use.6 7

Circulation, Volume XXXVII, June 1968 965

 966 SCHUMACHER ET AL.
Table 1
Hemodynamic Effects of 50 mg of Lidocaine (Group 1)
Patient Time Hr Mean art pr CI LVEDP SvI SWI dp Idt
L.L. 0 98 114 3.17 11 32 66.2 100
BSA-2.08 5 97 112 2.70 8 28 60.2 94
Age-66 yr 10 91 112 2.77 8 30 62.4 91
ASHD 15 96 106 2.98 8 31 62.8 94
30 92 98 2.98 10 32 62.2 123
W.C. 0 84 84 2.37 2 28 37.2 100
BSA-1.58 5 85 92 2.25 2 26 35.4 109
Age-73 yr 10 83 90 2.79 3 34 47.6 120
PMD 15 83 92 2.50 2 30 37.9 115
30 82 84 1.85 3 23 31.6 132
H.B. 0 63 95 3.06 8 49 70.0 100
BSA-1.88 5 64 100 3.14 9 49 74.0 93
Age-58 yr 10 66 92 3.41 7 48 68.5 97
PMD 15 65 92 2.84 4 44 61.6 110
30 64 98 2.65 7 41 61.3 110
J.W. 0 84 81 2.24 23 27 22.8 100
BSA-1.76 5 84 80 2.13 21 25 20.7 106
Age-52 yr 10 84 78 2.28 20 27 21.7 106
PMD 15 76 73 2.11 18 28 23.6 100
30 68 70 1.92 16 28 23.6 87
Key: BSA = body surface area in M2; ASHD = arteriosclerotic heart disease; PMD = primary
myocardial disease.
Time = time in minutes after drug injection with 0 representing the control period; HR =
heart rate in beats/min; Mean art pr = mean arterial pressure in mm Hg; CI = cardiac index
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in L/min/m2; LVEDP = left ventricular end-diastolic pressure in mm Hg; SVI = stroke volume
index in mI/M2; SWI = left ventricular stroke work index in g-m/m2; dp/dt = maximum rate
of rise of left ventricular pressure as per cent of control.

Lidocaine, best known as a local anesthetic,
has been found to be effective in the treat-
ment of many tachyarrhythmias,3 13 and
initial studies on the hemodynamic effects of
this agent indicated that it had distinct ad-
vantages over other commonly used anti-ar-
rhythmic drugs when administered intrave-
nously. In animals cardiac output has been
found to increase,14 and in man arterial
pressure generally is little affected by the
administration of therapeutic doses of lido-
caine.3 9 10 13,15 In addition, Harrison and
associates3 reported that myocardial con-
tractile force measured directly in patients
at the time of corrective cardiac surgery was
not affected significantly by this agent. How-
ever, more recently Nelson and Harrison'6
observed that lidocaine does diminish the
force of isometric contraction in the isolated
papillary muscle preparation, and Austen and
Moran17 have demonstrated a negative ino-
tropic effect in dogs.
The following study was undertaken to
provide information concerning the hemo-
dynamic effects of lidocaine in unanesthetized
humans and in particular to observe its effect
on left ventricular function. Furthermore, it
was proposed that these effects be examined
in subjects who would most likely receive this
agent therapeutically, for example, patients
with heart disease, and that the doses used be
those which are commonly used in the treat-
ment of arrhythmias.
Methods
Twelve male patients, ranging in age from 33
to 73 years (average, 52 years), were the
subjects of this study. Three patients had hyper-
tensive cardiovascular disease, two had arterio-
sclerotic heart disease with angina pectoris, and
the remainder were believed to have primary
Circulation, Volume XXXVII, June 1968
 HEMODYNAMIC EFFECTS OF LIDOCAINE 967
Table 2
Hemodynamic Effects of 100 mg of Lidocaine (Group 2)
Patient Time Hr Mean art pr CI LVEDP SvI SWI dp/dt
L.H. 0 109 81 1.30 16 12 11.8 100
BSA-1.71 5 107 87 1.37 27 13 12.5 72
Age-58 yr 10 106 83 1.35 19 13 13.5 90
ASHD 15 106 80 1.31 14 12 11.9 92
30 107 77 1.43 7 13 12.0 78
J.B. 0 73 109 2.10 11 29 45.8 100
BSA-1.74 5 84 116 2.10 16 25 37.4 92
Age-49 yr 10 85 118 2.04 16 24 37.7 112
HCVD 15 84 120 1.90 15 23 35.0 108
30 84 115 2.16 13 26 41.6 124
A.B. 0 126 84 3.03 22 24 22.9 100
BSA-1.61 5 134 83 3.12 20 23 21.2 97
Age-40 yr 10 130 80 3.28 17 25 24.7 112
PMD 15 129 80 3.40 20 26 23.0 108
30 124 78 3.25 15 26 24.6 97
W.G. 0 87 85 3.40 6 39 44.0 100
BSA-1.69 5 84 82 3.40 9 41 41.0 77
Age-49 yr 10 81 85 3.60 44
PMD 15 88 87 3.12 9 35 41.0 115
30 92 84 3.13 4 34 35.0 109
D.B. 0 95 80 1.83 30 19 13.9 100
BSA-1.96 5 96 69 1.51 27 16 10.0 86
Age-33 yr 10 89 72 1.27 29 14 10.3 97
PMD 15 93 78 1.95 31 21 15.4 109
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30 92 78 2.22 31 24 18.4 101

H.M. 0 109 117 2.47 22 23 32.1 100
BSA-1.82 5 113 115 2.19 23 19 24.3 89
Age-43 yr 10 110 117 2.24 23 20 24.7 92
HCVD 15 109 115 2.01 22 18 24.0 98
30 109 117 2.41 24 22 28.8 93
G.G. 0 96 143 2.99 7 31 63.8 100
BSA-1.95 5 98 149 2.87 10 29 63.0 110
Age-46 yr 10 102 155 2.65 9 26 57.6 104
HCVD 15 98 149 2.67 11 27 60.0 122
30 104 147 3.30 11 32 68.6 115
H.S. 0 88 96 2.28 20 26 33.4 100
BSA-1.91 5 90 109 2.38 22 26 36.0 128
Age-58 yr 10 86 106 2.45 24 29 34.0 107
PMD 15 87 106 2.60 23 30 36.9 107
30 86 100 2.55 15 30 39.5 134
For abbreviations, see table 1. HCVD = hypertensive cardiovascular disease.

myocardial disease (tables 1 and 2). All patients
but L. L. and G. G. had radiographic evidence
of cardiomegaly, a history of congestive heart
failure, and were receiving a digitalis glycoside
at the time of the study. Patient G. G. (table
2) had electrocardiographic evidence of left ven-
tricular hypertrophy. All patients were in sinus
Circulaion, Volume XXXVII, June 1968
rhythm, and none had clinical evidence of
congestive heart failure at the time of the study.
All studies were performed in the postabsorptive
state with the patient in the supine position.
Secobarbital, 100 mg, was given orally 60 to 90
min before the procedure. Following diagnostic
right and left heart catheterization, catheters
 968 SCHUMACHER ET AL.

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Figure 1

The effect of lidocaine on hemodynamic variables assessing left ventricular function. For
abbreviations, see text. Values represent mean values + standard error of the mean. Open cir-
cles connected by broken lines indicate values for patients receiving 50 mg of lidocaine; closed
circles connected by solid lines, values for those receiving 100 mg. Abscissa represents control
period (C) and time in minutes after drug injection.

were left in the main pulmonary artery for
purposes of injection and in the left ventricle
for the recording of pressure. Cardiac output
was determined by the indicator-dilution method.
Indocyanine-green dye was injected and rapidly
flushed into the pulmonary artery while blood
from the brachial artery was withdrawn through
a Gilford densitometer. The maximum rate of
rise of left ventricular pressure was measured
using an R-C differentiating circuit with a 15-Hz
filter. A standard limb lead of the electrocardio-
gram and the brachial arterial pressure were
recorded with the hemodynamic variables on a
multi-channel oscillograph. The midthoracic level
was used as the zero reference point for intra-
vascular pressure.
After systemic arterial pressure, heart rate, and
left ventricular end-diastolic pressure (LVEDP)
had remained constant for 15 to 20 min, 50 mg
of lidocaine was injected as a single bolus into
Circulation, Volume XXXVII, June 1968
 HEMODYNAMIC EFFECTS OF LIDOCAINE
the pulmonary artery of four patients (group 1).
All measurements were then repeated 5, 10, 15,
and 30 min after drug injection. Since no adverse
effects were noted with this dose of lidocaine,
the next eight patients (group 2) received 100
mg of lidocaine injected as a single bolus; mea-
surements were repeated as above.
Stroke work index (SWI) in g-m/m2 was cal-
culated from the following formula:
-;XA7T-SVI X (LVSP - LVEDP) X 1.36
3)vVy
100
where SVI means the stroke volume index in
milliliters per square meter, LVSP is the mean
left ventricular pressure during ejection in mm
Hg determined planimetrically, and LVEDP is
the left ventricular end-diastolic pressure in mm
Hg.
Results
Group 1
The individual hemodynamic data before
and after injection of 50 mg of lidocaine are
presented in table 1, while the mean values
are illustrated in figure 1.
In three patients heart rate was essentially
unchanged or demonstrated only a slight fall
following drug administration, while a fall of
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16 beats/min was observed at the 30-min
period in the remaining patient. Mean arterial
pressure remained relatively constant in two
patients, but had decreased by 16 and 11 mm
Hg at the 30-min period in the other two.
Neither patient developed symptoms of ar-
terial hypotension, and the arterial pressure
gradually returned to the control values with-
out therapeutic intervention. Cardiac index
(CI) at rest was reduced to <2.5 L/min/m2
in two patients. After the injection, CI was
relatively unchanged in all patients during
the first 15 min, but a small decline from the
control value was observed in four patients
at the 30-min period, the maximum decrease
being 0.52 L/min/m2. Left ventricular end-
diastolic pressure (LVEDP) at rest exceeded
normal (>12 mm Hg) in only one patient.
Lidocaine did not result in a significant in-
crease in LVEDP in any patient and, in
fact, a significant fall occurred at the 30-min
period in the patient with the highest resting
LVEDP. In two patients small reductions in
SVI of 2 and 4 ml/m2 occurred at the 5-min
Circulation, Volume XXXVII, June 1968
969
period and thereafter returned to control
values. In the remaining two patients maxi-
mum decreases in SVI of 5 and 8 mI/m2 oc-
curred at the 30-min period. SWI also de-
creased in each patient at some time after
drug injection with the greatest decrease be-
ing 8.7 g-m/m2. In two patients the maximum
decrease in SWI occurred at the 5-min period
whereas in the remaining two this was noted
at 30 min. The maximum rate of rise of left
ventricular pressure fell below the control
value in three patients, the greatest decrease
being 13% which occurred at the 30-min pe-
riod. The reduction in dp/dt in the remaining
two patients did not exceed 10% and, by the
30-min period, values exceeding the control
were observed.
Group 2
The individual hemodynamic data before
and after 100 mg of lidocaine are given in
table 2 and the mean values are illustrated in
figure 1. The mean values for LVEDP, SWI,
and maximum dp/ dt at the 10-min period
include observations on only seven patients.
However, recalculation of mean values for all
the variables using data from only these seven
patients did not appreciably alter the results.
Changes in heart rate were variable after
lidocaine, the maximum increase observed
being 12 beats/min and the maximum de-
crease 6 beats/min. The average heart rate
at all periods after lidocaine was essentially
unchanged from the control rate which av-
eraged 98 + 6 (SE) beats/min. The response
of mean arterial pressure to lidocaine also
varied among the patients, although the
average value at each period was quite similar
to the control of 99 + 8 mm Hg. The maxi-
mum decrease in mean arterial pressure
observed in any patient was 11 mm Hg which
occurred at the 5-min period and which had
returned to essentially control values at the
15-min period in this patient. Cardiac index
was reduced at rest in five patients and
averaged 2.43 ± 0.25 L/min/m2. After lido-
caine the average cardiac index was essential-
ly unchanged, and the maximum decrease
observed in any patient was 0.56 L/min/m2.
 970
LVEDP at rest was elevated in five patients
and averaged 17 3 mm Hg. The response of
LVEDP to lidocaine was quite variable. How-
ever, an elevation of LVEDP to abnormal
levels occurred in only one of the patients in
whom the resting value was normal. In the
five patients with elevated LVEDP at rest a
further rise after lidocaine occurred in four.
In one of these latter patients an increase of
11 mm Hg was observed whereas in the
others the increase did not exceed 4 mm Hg.
Lidocaine produced a decrease in SVI in six
of eight patients. However these changes
generally were quite small averaging only
1 ml/m2 below control through the 15-min
period. In all but two of these patients SVI
had returned to near control values by the
30-min period which averaged 1 ml/m2 above
control. Similarly, SWI decreased at some
time during the first 15 min after lidocaine in
the same six patients and in four returned
toward their respective control values by 30
min. The maximum decrease in the average
SWI occurred at the 10-min period, having
decreased from the control average of 33.5
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g-m/m2 at rest to 28.9 g-m/m2. This decrease
however is somewhat magnified by the failure
to obtain measurements at the 10-min period
in one patient. Excluding this patient the
average decrease in SWI between the control
and 10-min periods was 3.0 g-m/m2. The max-
imum rate of rise of left ventricular pressure
decreased by more than 5% in five patients.
In each of these patients the maximum de-
crease occurred at the 5-min period and in
four of these patients maximum dp/dt had
returned toward control values by 30 min.
In the remaining one of these four patients,
dp/dt had returned to near control values by
the 15-min period but, in association with a
marked fall in LVEDP, decreased again at the
30-min period. The average decrease in dp/
dt for the group was small, averaging 4% at
the 5-min period and thereafter exceeding
control values.
Discussion
It was the purpose of the present investiga-
tion to determine the hemodynamic effects of
SCHUMACHER ET AL.
lidocaine and in particular the effect of the
drug on left ventricular function in man. Al-
though changes in arterial pressure, heart
rate, and cardiac output can be detected
with relative ease and reliability in man, de-
tection of alterations in left ventricular func-
tion presents significantly greater problems.
Several investigators however have demon-
strated that the relationship of the mechanical
work performed by the ventricle, that is,
SVI and SWI to the left ventricular end-
diastolic volume as reflected in the LVEDP,
is a useful measure of myocardial func-
tion.18-24 Thus, an increase in SVI and SWI,
or both, from the same or diminished LVEDP
indicates an increase in the contractile state of
the myocardium whereas a decrease in SVI
and SWI, or both, with the same or increased
LVEDP indicates depressed myocardial func-
tion. Therefore, this relationship was used in
the present study to assess the effects of lido-
caine on left ventricular function. In addition
the maximum rate of rise of left ventricular
pressure also was measured since changes in
the contractile state of the ventricle can occur
which are reflected only in changes in the
velocity of myocardial contraction.2'
Interpretation of the data from the patients
given 50 mg of lidocaine is difficult because
of the variable results obtained in this small
number of patients. However, since it was
not the purpose of this investigation to study
dose response relationships of lidocaine and
since no major untoward hemodynamic ef-
fects occurred in this group of patients, we
elected not to include a larger number of
patients. Two patients given 50 mg of lido-
caine did develop decreases in mean arterial
pressure of 16 and 11 mm Hg although this
was not accompanied by symptoms, was
relatively short-lived, and did not require
therapeutic intervention. A relatively small
decrease in cardiac index was observed in
each patient, the maximum being 0.52 L/min/
m2, whereas a significant rise in LVEDP did
not occur in any patient. Unequivocal evi-
dence of a myocardial depressant action with
this dose of the drug was not obtained in
Circulation, Volume XXXVIl, June 1968
 HEMODYNAMIC EFFECTS OF LIDOCAINE
any patient. Changes in SVI and SWI gen-
erally paralleled the changes in LVEDP, and
in the two patients in whom changes in these
variables suggested a depression of myo-
cardial function, an increase in maximum dp/
dt occurred at that time. Furthermore in the
two patients in whom maximum dp/dt fell
after lidocaine, the decreases were small, 9
and 7%, and in one this could be attributed to
a simultaneous reduction in heart rate and
LVEDP.25, 26
The administration of 100 mg of lidocaine
to eight patients also resulted in variable but
generally small changes in all hemodynamic
variables, none of which was significantly
different statistically from its respective con-
trol at any time period. The maximum
decrease in mean arterial pressure in any
individual was 11 mm Hg which occurred in
one patient at the 5-min period and which
had returned to control values by the 15-min
period. The maximum decrease in CI in any
patient was 0.56 L/min/m2 which occurred
at the 10-min period and which had returned
to control values by the 15-min period. In
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only one patient was a marked increase in
LVEDP observed (11 mm Hg), and this also
quickly returned toward control values. None
of the patients developed symptoms following
lidocaine injection.
These results are in agreement with pre-
vious reports concerning the effect of this drug
on systemic arterial pressure.3 9,10,13,15 The
observation that there was no statistically
significant change in SVI, SWI, dp/dt, or
LVEDP from their respective control values
would indicate that this agent did not depress
myocardial function. This would be in accord
with the observation of Harrison and asso-
ciates3 who measured right ventricular con-
tractile force in man but at variance with
studies using dogs17 or isolated muscle
preparations.16
However examination of individual re-
sponses in the group 2 patients revealed that
left ventricular function was depressed by
lidocaine in some patients. Three patients
(J. B., W. G., and H. M.) responded to the
drug with an increase in LVEDP whereas
Ciculation, Volume XXXVII, June 1968
971
maximum dp/dt and SWI fell in each and
SVI declined in two. In an additional patient
(L. H.), maximum dp/dt fell and SVI and
SWI increased only slightly in spite of an
increase of 11 mm Hg in LVEDP. Thus the
effect of 100 mg of lidocaine on myocardial
function in patients with heart disease is
variable. Of equal or greater importance how-
ever is the observation that, even when im-
pairment of left ventricular function did occur,
it was not of sufficient magnitude to produce
symptoms or reduce the cardiac output and
the effect was short-lived.
It is of interest that the response to lido-
caine was not influenced by the type of heart
disease or its severity as judged by the resting
CI and LVEDP. However the small number
of patients studied would not permit a
definitive conclusion in this regard. Certainly
it must be appreciated that a more pro-
nounced effect might occur in patients with
more advanced heart disease or in those
receiving larger doses of this drug. Neverthe-
less, it would appear from this study that the
injection of lidocaine in amounts commonly
used in the treatment of arrhythmias exerts
remarkably few, if any, adverse hemodynamic
effects of clinical significance in man.
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Circulation, Volame XXXVII, June 1968