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1144
Prediction of Defibrillation Success
From a Single Defibrillation Threshold
Measurement With Sequential Pulses and
Two Current Pathways in Humans
Douglas L. Jones, PhD, George J. Klein, MD, FRCP(C), FACC,
Gerard M. Guiraudon, MD, FRCS(C), FACC, Arun D. Sharma, MD, FRCPC, FACC,
Raymond Yee, MD, FRCP(C), and Michael J. Kallok, PhD, PE
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The ultimate aim of defibrillation testing is to predict consistent defibrillation. This study tested
the hypothesis that defibrillation success could be predicted from a single measurement of
defibrillation threshold. We measured defibrillation threshold by using three patch electrodes
and a standard protocol intraoperatively in 49 patients undergoing arrhythmia surgery. Each
patient was then assigned to one of five energy subgroups (0.5, 1.0, 1.5, 2.0, or 2.5 times
defibrillation threshold) for a single shock (followed by a rescue shock if necessary) for a
subsequent ventricular fibrillation episode. A curve relating percent success to energy was then
constructed for the group. Defibrillation threshold averaged 4.7 2.98 J for the group
(mean + SD). There was a curvilinear relation between the energy of the defibrillation threshold
ratio test shock and percent success: 33.3%, 58.3%, 81.8%, 91.7%, and 100% at mean
defibrillation threshold ratios of 0.56 0.14, 1.02 0.07, 1.53 0.14, 1.88 0.09, and 2.60 0.14,
respectively. We conclude that consistent defibrillation is predictable from a single measurement of defibrillation threshold. Furthermore, for an individual patient, a safety margin of 2.6
times defibrillation threshold should approximate 100% successful defibrillation for a single test
shock. (Circulation 1988;78:1144-1149)
I mplantation of an automatic defibrillation device
necessitates an estimate of the energy requirements for defibrillation to ensure that the
device will defibrillate consistently at its maximum
output. In experimental animals, many defibrillation attempts may be performed, and the relation
may be plotted between percentage of successful
defibrillation and defibrillation energy delivery. 1-3
In patients, the number of defibrillation episodes is
limited, and defibrillation threshold is a more
readily attainable measure.4-6 The purpose of this
From the Departments of Medicine and Physiology, The
University of Westem Ontario, and Department of Medicine,
University Hospital, Department of Cardiovascular and Thoracic Surgery, University Hospital, London, Ontario, Canada;
and Medtronic Incorporated (M.J.K.), Minneapolis, Minnesota.
Supported in part by The Medical Research Council of Canada, The Heart and Stroke Foundation of Ontario, and Medtronic Incorporated. D.L.J., A.D.S., and R.Y. are Ministry of
Health Career Scientists. G.J.K. is a Research Associate of the
Heart and Stroke Foundation of Ontario.
Address for correspondence: Dr. D.L. Jones, Department of
Medicine and Physiology, The University of Western Ontario,
London, Ontario, Canada N6A 5C1.
Received January 21, 1988; revision accepted May 26. 1988.
study was to evaluate how a single defibrillation
threshold could be used to estimate a margin of
safety for successful defibrillation and to provide
'"acceptable and unacceptable" criteria for a specific lead system and device.
Patients and Methods
Patient Population
Fifty-one successive volunteer patients undergoing arrhythmia surgery (33 men and 18 women)
provided written and verbal, informed consent in
accordance with the regulations of the Health Sciences Standing Committee on Human Research of
The University of Western Ontario, London, Ontario, Canada. The mean age was 31.7+9.4 years
(range, 19-54 years) with mean weight 73.4 + 13.5
kg (range, 51.1-109.6 kg). Patients were randomized to one of five test-energy subgroups (0.5, 1.0,
1.5, 2.0, or 2.5 times defibrillation threshold).
Surgical Procedure
Patients were prepared for surgery, and the heart
was exposed by a median sternotomy. The heart
Jones et al Prediction of Percent Defibrillation
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FIGURE 1. Diagram of electrode locations on an anterior view of the heart. First pulse was passed between
electrode a (anode) on the anterior right ventricle and
electrode b (common cathode) on the left lateral ventricle. Electrode on the posterior right ventricle was the
anode for the second pulse of the sequential pulse shock.
c
was prepared for cardiopulmonary bypass in patients
as needed.4 Epicardial mapping verified the site of
origin of the arrhythmia before the initiation of the
experimental defibrillation protocol. Three electrode patches were sutured on the heart (three TX7
mesh, or two 6889 and one 6890 coil electrodes,
Medtronic, Minneapolis, Minnesota), on the ventricular epicardium of the left lateral free wall,
posterior right free wall, and anterior right free wall
(Figure 1). Current for the first pulse of the sequential shock was delivered between the electrode on
the anterior right ventricle (anode) and the left
lateral electrode (common cathode). The anode for
the second pulse of the sequential shock was the
right posterior electrode.
Leads from the electrodes were interfaced to
two custom-designed defibrillators. The output
from the defibrillators delivered trapezoidal pulses
at preset energy increments. Each pulse of the
sequential shock was approximately 2.5 msec in
duration separated by 0.2 msec.7-10
Fibrillation and Defibrillation
Ventricular fibrillation was induced by passing a
low-energy alternating current directly to the heart
by the fibrillator available in the operating room.
1145
After a minimum ventricular fibrillation of 10 seconds, defibrillation was attempted. The defibrillation threshold was determined as follows. The initial defibrillation setting was at a stored voltage of
300 V, which corresponded to an estimated energy
delivery of approximately 3 J. Subsequent shocks in
the fibrillation episode were at increments of approximately 1 J for shocks up to 10 J, then at increments
of 2.5 J for shocks up to 15 J until defibrillation was
successful. If the first shock of a fibrillation episode
was successful, an additional episode was allowed
that started at a stored voltage of 170 V, which
corresponded to a calculated energy delivery of
approximately 1 J. Increments of 1 J were used until
defibrillation was successful. Defibrillation threshold was defined as the minimum energy required to
cause defibrillation.4
Once defibrillation threshold had been determined, estimated stored voltage for a test shock
was calculated, which would correspond to that
necessary to deliver the randomly selected ratio of
defibrillation threshold energy for that patient.
The initial stored voltage was set at the test shock
voltage level. Ventricular fibrillation was reinduced after 5 minutes, and the defibrillation test
shock was delivered and was followed immediately by rescue shock if necessary. A maximum of
three ventricular fibrillation episodes, each separated by 5 minutes, were allowed. The total potential duration of circulatory arrest for all fibrillation
episodes in a single patient averaged 44.8+12.4
seconds (range, 29-71.5 seconds).
Energy Delivery Determination
Scaled output waveforms from the defibrillators
were delivered to an analog-to-digital converter
mounted in a portable personal computer. The
computer program allowed on-line display of waveforms immediately after the delivery of a shock, and
after successful defibrillation, it permitted determination of the peak voltage, peak current, impedance, duration of each pulse, energy delivery from
each pulse, and total delivered energy for every
shock. Energy was calculated by the integrated area
under the curve and the correction for the logarithmic decay of the capacitive discharge.4
Statistical Analysis
Analysis of the difference in the total energy,
leading edge peak voltages, and currents for each
energy ratio was made by analysis of variance."
Data are presented as the mean + SD. A probability
of 0.05 or less was considered significant.
Results
Two patients were not included in the analysis
because of technical problems. The remaining 49
patients had defibrillation thresholds determined
and were administered one of the five energy ratio
test shocks. Defibrillation threshold for the 49
patients averaged 4.7 + 2.9 J.
Circulation Vol 78, No 5, November 1988
1146
3-0
s
4
LUC
-1
2-5
0
0
0 2-0
Ir
1
u
U.
r
I1.5
<0.75 1.0 1.5 2.0 >2.25
DFT RATIO
LL.
1-0
FIGURE 3. Bar graphs of mean values of test shock-
9i
-I'---
:1
delivered, leading-edge peak voltage for the first (Panel
A) and second (Panel B) pulses. End bars represent ± SD.
Numbers of patients in each group from left to right are
6, 12, 11, 12, and 8, respectively.
0-5
1
U
-
-r
SUCCESSFUL
-
1.5 2.0 >2.25
DFT RATIO
(0.75 1.0
1-
UNSUCCESSFUL
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FIGURE 2. Plot of energy ratio of all shocks delivered to
all patients. Note that shocks below defibrillation threshold (<DFT ratio= 1.0) were mostly unsuccessful. In contrast, shocks equal to or greater than defibrillaton threshold (-DFT ratio-1.0) were mostly successful. By
definition, there are 51 successful shocks at 1.0 times
defibrillation threshold because this was the criterion for
defibrillation threshold.
Although the value for the mean defibrillation
threshold of the group receiving test shocks greater
than 2.25 times defibrillation threshold was the lowest, there was no statistical difference between the
groups (F= 2.01 at 4 and 44 df, p>0.05) of the 51
patients, 50 of whom were undergoing surgical ablation of the accessory pathway for Wolff-ParkinsonWhite syndrome. The additional patient was having
an internal defibrillator implanted. His defibrillation
threshold was 1.41 J, and he was successfully defibrillated with the test shock of 3.56 J.
Figure 2 represents the delivered energy ratio of
all shocks delivered to the patient population. The
predominance of unsuccessful shocks fell below the
defibrillation threshold, whereas most successful
shocks were with ratios equal to or greater than the
defibrillation threshold.
Mean peak voltages for the first and second pulse
of the test shock ranged from approximately 200 to
450 V (Figure 3). There was a slight diminution in
the peak voltage of those patients receiving more
than a 2.25 times defibrillation threshold. This was
due to the inaccuracy of calculation of the defibrillation threshold ratio and to not attempting to
correct stored voltage of the test shock for different
impedances. These inaccuracies were greatest in
those patients in whom defibrillation threshold was
approximately 1-2 J. This resulted in more patients
with low defibrillation threshold in the highest group.
The corresponding mean peak current of these
test shocks was from 2.5 A to a maximum of
approximately 6.5 A. There was a slight diminution
in the mean peak current for the patients receiving
greater than 2.25 times defibrillation threshold ratio
(Figure 4).
CL
0
0
0
E
FIGURE 4. Bar graphs of mean values of test shockdelivered, leading-edge peak current for the first (Panel
A) and second (Panel B) pulses. End bars represent
±SD. Numbers of patients in each group from left to
right are 6, 12, 11, 12, and 8, respectively.
Iz
Iz
W
cc
W
cc
LL
CL
UJ
<0.75 1.0
1.5
2.0 >2.25
DFT RATIO
DFT RATIO
Jones et al Prediction of Percent Defibrillation
1147
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W
6I.-
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o 0~~~~~~~~~~~~
6
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z~~~~~~~
0<0.75 1.0 1.5 2.0 >2.25
DFT RATIO
0<0.75 1.0 1.5 2.0 >2.25
DFT RATIO
0
1.5 2.0 >2.25
DFT RATIO
<0.75 1.0
FIGURE 5. Bar graphs of mean values for test shock-delivered energy for thefirst (Panel A) and second (Panel B) pulses
and total shock (Panel C). End bars represent ±SD. Numbers of patients in each group from left to right are 6, 12, i1,
12, and 8, respectively.
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The resultant calculated mean delivered energy
of the test shocks ranged from approximately 2 J for
the lowest ratio to a maximum of approximately 9.5
J for the maximum total energy delivered (Figure 5).
Of note, this total energy was delivered to two
different pathways. Thus, the delivered energy
through each pathway was one half of the total
(Figure 5).
Defibrillation threshold for the 49 patients averaged 4.7 + 2.9 J. There was a difference noted
depending on the particular electrode configuration.
The average defibrillation threshold for the coil
electrode configuration was slightly, but significantly, lower than that of the mesh electrode configuration (Figure 6).
A curve relating the percentage of successful
defibrillation to test shock-delivered energy was
constructed for the group (Figure 7A). When plotted as a log of the defibrillation threshold ratio, the
plot was linear and ranged from approximately 35%
at 0.5 times defibrillation threshold to 100% at
approximately 2.6 times defibrillation threshold.
After having determined that defibrillation threshold with the coil configuration was slightly lower
than that of the mesh electrode configuration, we
replotted data with only test-shock data from patients
with the coil electrodes (Figure 7B). By this method,
the plot had a plateau with 100% successful defibrillation between 2.0 and 2.5 times defibrillation threshold. Again, the plot was linear between the minimum of approximately 35% at the 0.5 times
defibrillation threshold and 100% at 2.0 times defibrillation threshold. Of note, these curves are constructed from the first shock only of the test sequence
and therefore are the percent success of the first
shock of the new fibrillation episode.
Discussion
This study demonstrates that defibrillation in
humans can be consistently achieved with threshold
energy averaging 4.7 J with coil and mesh electrode
systems. These results are consistent with our previous studies in animals and humans in which we
found low thresholds with patch electrodes and
sequential pulse technique for defibrillation. 12-14
For patients receiving an implanted automatic
defibrillator, it is essential to estimate the energy
necessary for consistent defibrillation and to predict
the safety margin available for a specific lead system and device. Several methods have been suggested for such determinations.2-4,15-18 However,
with patient studies, it is not reasonable to have a
large number of defibrillation episodes. On the
other hand, a single defibrillation threshold determination is rapid, easy to obtain, and, thus, more
0
0
~1
Z
4
mI-
COIL
MESH
FIGURE 6. Bar graph of means of total delivered energy
at defibrillation thresholdfor all patients that had current
delivered through coil (n=35) or mesh (n=14) electrodes.
End bars represent +SD. Differences between the two
means, although small, are statistically significant
(t=-2.43, p<O.05).
Circulation Vol 78, No 5, November 1988
1148
100.gA
.0- n=8
1001
n-6
n=5
P ----D
B
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n=11
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401
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DFT RATIO
FIGURE 7. Plots relating the test shock defibrillation threshold (DFT) energy ratio to percentage of successful defibrillation. Note that the
relation to the log dose ratio is linear to 100%
success at 2.6 times defibrillation threshold with
the combined data (Panel A) and has a plateau
at 100% between 2.0 and 2.6 times defibrillation
threshold with the coil electrode data only (Panel
B). Straight line was drawn to connect the
maximum and minimum points.
U)
L)
n-12
n-6
801
n= 6
0.5
1.0
1.5 2.0 2.5
DFT RATIO
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feasible considering the restrictions of the operating
room environment. This study suggests that a single
measurement of defibrillation threshold can be used
to predict successful defibrillation from the first
shock of subsequent ventricular fibrillation episodes under similar circumstances in the same
patient.
In this study, 2.6 times defibrillation threshold
achieved 100% successful defibrillation with the
first shock. Of note, the shape of the curve between
percent success and the defibrillation threshold
ratio depended on the particular electrodes used.
This suggests that in addition to surface area of
electrodes, the efficiency of a particular electrode
system may also be important in determining the
shape of a curve of percent success and defibrillation threshold ratio. Direct cardiac shocks with
single-pulse current delivery with either intravascular catheters4,5 '5 17 or an epicardial system'3. 5.16
have been successful in humans when energies
range from 15-35 J and when there is a relatively
shallow slope for the dose-response curve. In the
present study, the slope was relatively steep, and
the maximum threshold with the coil electrode
configuration was approximately 14 J. The electrode configuration of this patient was found to
have a very low impedance, suggesting a partial
short in the current delivery to the heart. The
remaining 34 patients in this group had defibrillation threshold energies below 7.5 J. In addition,
100% success with the first test shock could be
achieved with energies of only 2.0 times defibrillation threshold with the coil electrodes.
Additional factors may influence defibrillation
success. Most patients (50 of 51) in this study had
no myopathology. Patients who are candidates for
an implanted device often have extensive myocardial pathology and ischemia, which may or may not
alter defibrillation threshold.6'19-25 Also, these studies were short term. The effects of long-term lead
placement and antiarrhythmic drug therapy on de-
fibrillation remains controversial3 25-29 and requires
further investigation.
Since Mirowski and colleagues30 and Denniston
and colleagues3' first described the concept of an
implantable defibrillator, there has been a great
interest in searching for the optimum electrode
configuration and the best method for predicting
defibrillation success. From these studies, we conclude that the sequential pulse shock with moderatesized electrodes provides acceptably low-energy
requirements for defibrillation. In addition, a single
measurement of defibrillation threshold can be used
to predict subsequent defibrillation for an individual
patient. The value of approximately 2.6 times defibrillation threshold should approximate 100% successful defibrillation with the first shock for the
electrode system. Finally, the determination of population curves of success and defibrillation threshold ratio may be valuable in estimating safety margin for any particular electrode system.
Acknowledgments
We thank the staff of OR #5 for their patients
and assistance. We also thank K. Clarke for
typing the manuscript.
References
1. Rattes MF, Jones DL, Sharma AD, Klein GJ: Defibrillation
threshold: A simple and quantitative estimate of the ability
to defibrillate. PACE 1987;10:70-77
2. Davy JM, Fain E, Dorian P, Winkle RA: The relationship
between successful defibrillation and delivered energy in
open chest dogs: Reappraisal of the "defibrillation threshold" concept. Am Heart J 1987;113:77-84
3. Fain ES, Billingham M, Winkle RA: Internal cardiac defibrillation: Histopathology and temporal stability of defibril-
lation energy requirements. JAm Coll Cardiol 1987;9:631-638
4. Jones DL, Klein GJ, Guiraudon GM, Sharma AD, Kallok
MJ, Bourland JD, Tacker WA: Internal cardiac defibrillation
in
man: Pronounced improvement with sequential pulse
delivery to two different lead orientations. Circulation 1986;
73:484-491
5. Klein GJ, Jones DL, Sharma AD. Kallok MJ, Guiraudon
GM, Sharma AD, Kallok MJ, Tacker WA, Bourland JD:
Internal cardiac defibrillation in man: Influence of cardiopulmonary bypass. Am J Cardiol 1986;57:1194-1195
Jones
Downloaded from http://circ.ahajournals.org/ by guest on June 11, 2017
6. Jones DL, Klein GJ, Guiraudon GM: Sequential pulse
defibrillation in man: Comparison of thresholds in normals
and those with cardiac disease. Med Instrum 1987;21:166-169
7. Bourland JD, Tacker WA, Wessale JL, Kallok MJ, Graf JE,
Geddes LA: Sequential pulse defibrillation for implantable
defibrillators. Med Instrum 1986;20:138-142
8. Jones DL, Klein GJ, Kallok MJ: Improved internal defibrillation with twin pulse energy delivery. Am J Cardiol 1985;
55:821-825
9. Jones DL, Sohla A, Bourland JD, Tacker WA, Kallok MJ,
Klein GJ: Internal ventricular defibrillation with sequential
pulse counter-shock in pigs: Comparison with single pulses
and effects of pulse separation. PACE 1987;10:497-502
10. Rattes MF, Jones DL, Sohla A, Sharma AD, Jarvis E, Klein
GJ: Defibrillation with the sequential pulse technique: Reproducibility with repeated countershocks. Am Heart J 1986;
111:874-878
11. Sokal RR, Rohlf FJ: Biometry. San Francisco, Calif, WH
Freeman, 1981, p 859
12. Jones DL, Rattes MF, Sohla A, Sharma AD, Klein GJ:
Internal cardiac defibrillation: Single and sequential pulses
and a variety of lead orientations. PACE 1988;11:583-591
13. Jones DL, Klein GJ, Guiraudon GM, Sharma AD: Sequential pulse defibrillation in man: Orthogonal sequential pulses
with 4 mesh electrodes versus single pulse with 2 mesh
electrodes. J Am Coil Cdrdiol 1988;1 1:590-596
14. Kallok MJ, Bourland JD, Tacker WA, Jones DL, Klein GJ,
Wessale JL: Optimization of epicardial electrode size and
implant site for reduced sequential pulse defibrillation thresholds. Med Instrum 1985;20:36-39
15. Mirowski M: Treatment of malignant ventricular tachyarrhythmias with the automatic implantable defibrillator. Int J
Cardiol 1983;2:409-413
16. Winkle RA, Stinson EB, Bach SM, Echt DS, Oyer P,
Armstrong K: Measurement of cardioversion/defibrillation
thresholds in man by a truncated exponential waveform and
an apical patch-superior vena caval spring electrode configuration. Circulation 1984;69:766-771
17. Zipes DP, Heger JJ, Miles WM, Mohamed Y, Brown JW,
Spielman SR, Prystowsky EN: Early experience with an
implantable cardioverter. N Engl J Med 1984;311:485-490
18. Reid PR, Mirowski M, Mower MM, Platia EV, Griffith LSC,
Watkins L Jr: Clinical evaluation of the internal automatic
cardioverter-defibrillator in survivors of sudden cardiac death.
Am J Cardiol 1983;51:1608-1613
19. Mirowski M, Mower MM, Gott IL, Brawley RK, Denniston
RH: Transvenous automatic defibrillator-preliminary clinical
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
et
al Prediction of Percent Defibrillation
1149
tests of its defibrillating subsystem. Trans Am Soc Artif Int
Organs 1972;18:520-525
Mower MM, Mirowski M, Denniston RH: Intraventricular
defibrillation in dogs with impaired coronary circulation
(abstract). Clin Res 1972;20:388
Tacker WA Jr, Geddes LA, Cabler PS, Moore AG: Electronic threshold for defibrillation of canine ventricles following myocardial infarction. Am Heart J 1974;88:476-481
Ruffy R, Schwartz DJ, Heib BR: Influence of acute coronary
artery occlusion on direct ventricular defibrillation in dogs.
Med Instrum 1980;14:23-26
Babbs CF, Paris RL, Tacker WA Jr, Bourland JD: Effects of
myocardial infarction on catheter defibrillation threshold.
Med Instrum 1983;17:18-20
Kerber RE, Pandian NG, Hoyt R, et al: Effects of ischemia,
hypertrophy, hypoxia, acidosis and alkalosis on canine
defibrillation. Am J Physiol 1983;244:H825-H831
Chang M-S, Inoue H, Kallok MJ, Zipes DP: Double and
triple sequential shocks reduce ventricular defibrillation
threshold in dogs with and without myocardial infarction. J
Am Coil Cardiol 1986;8:1393-1405
Jones DL, Sohla A, Klein GJ: Internal cardiac defibrillation
threshold: Effect of acute ischemia. PACE 1986,9:322-331
Pearson JW, Redding JS: Epinephrine in cardiac resuscitation. Am Heart J 1963;66:210-214
Deeb MG, Hardesty RL, Griffith BP, Thompson ME, Heilman MS, Myerowitz RL: The effects of cardiovascular drugs
on the defibrillation threshold and the pathological effects on
the heart using an automatic implantable defibrillator. Ann
Thorac Surg 1983;35:361-366
Ruffy R, Schechtman K, Monje E: P-Adrenergic modulation
of direct defibrillation energy in anaesthetized dog heart. Am
J Physiol 1985;248:H674-H677
Mirowski M, Mower MM, Staewen WS, Tabatznik B,
Mendeloff AI: Standby automatic defibrillator. Arch Int Med
1970;126: 158-161
Denniston RH, Mower MM, Mirowski M: Automatic standby
defibrillator (abstract). J Assoc Adv Med Instrum 1971;5:110
Rattes MF, Sharma AD, Klein GJ, Szabo T, Jones DL:
Adrenergic effects on internal cardiac defibrillation threshold. Am J Physiol 1987;253:H500-H506
Szabo TS, Jones DL, McQuinn RL, Klein GJ: Flecainide
acetate does not alter the energy requirements for direct
ventricular defibrillation using sequential pulse defibrillation
in pigs. J Cardiovasc Pharmacol 1988 (in press)
KEY WORDS * implantable automatic defibrillator * sequential
pulse defibrillation * defibrillation threshold * defibrillation
prediction
Prediction of defibrillation success from a single defibrillation threshold measurement
with sequential pulses and two current pathways in humans.
D L Jones, G J Klein, G M Guiraudon, A D Sharma, R Yee and M J Kallok
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Circulation. 1988;78:1144-1149
doi: 10.1161/01.CIR.78.5.1144
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