Download on Cardiac Refractory Periods

Effects of Cycle Length
Cardiac Refractory Periods
in Man
The
on
By PABLO DENES, M.D., DELON
RAYMOND J. PIETRAS, M.D,
RAMESH DHINGRA, M.D.,
KENNETH M. ROSEN, M.D.
WU, M.D.,
AND
SUMMARY
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The effects of pacing-induced changes in cycle length on the refractory periods of the atrium,
A-V node and His-Purkinje system were studied in 24 patients using the extra stimulus technique.
Refractory period determinations were made at two or more cycle lengths in all patients. Slopes
relating cycle length and refractory periods were calculated using the least squares method.
Both the effective and functional refractory periods (ERP and FRP) of the atrium shortened
with decreasing cycle lengths, with a mean slope of +0.155 and +0.129 respectively. A-V nodal
ERP lengthened (mean slope, -0.177) while A-V nodal FRP shortened slightly (mean slope,
+0.126). Bundle branch refractory periods as well as relative refractory periods of the His-Purkinje system also decreased, with mean slopes of +0.270 and +0.360, respectively. The ERP of
the A-V node at any cycle length was related to the A-H at that cycle length (r = +0.646,
P < 0.001).
The responses of the human heart to changes in cycle length are generally similar to those
previously described in the animal laboratory. Such information contributes to our understanding
of electrocardiographic phenomena such as aberrant conduction.
Additional Indexing Words:
His bundle electrogram
Functional refractorv period
Premature atrial impulses
Relative refractory period
IN ISOLATED HEART TISSUE, as cycle length
changes, action potential durations and refractory periods are altered.' Mendez et al., working
with intact denervated canine hearts, noted that the
functional refractory periods of the atrium, A-V
node, His bundle, and bundle branches shortened
as cycle length was decreased.2 These changes were
least apparent in the A-V node and most striking in
the His-Purkinje system.
The purpose of the present study was to examine
the effect of pacing-induced changes in cycle length
Effective refractory period
Aberrant conduction
on the refractory periods of the atrium, A-V node,
and His-Purkinje system in man.
Methods
Refractory periods were determined in 24 patients
during diagnostic cardiac catheterization. All patients
were in sinus rhythm and had normal QRS duration
(0.10 sec or less) and normal conduction intervals as
determined by His bundle recording technique.3 The
mean age of the patients was 41 years (range 15-77),
and there were 18 males and six females. Clinical and
electrocardiographic data as well as control conduction
intervals are summarized in table 1. Only two patients
had received cardioactive drugs within the week prior
to study (procaine amide in patient 4 and digoxin in
patient 8). Both drugs were discontinued 48 hours
prior to study in these latter two patients.
His bundle electrograms were recorded with a
tripolar catheter placed close to the tricuspid valve.4
Atrial electrograms were recorded through two electrodes of a quadripolar catheter positioned fluoroscopically against the lateral wall of the high right atrium.
The remaining two electrodes were used for atrial
pacing. Interelectrode distances were one centimeter.
Recordings were obtained on a multichannel oscilloscopic recorder (Electronics for Medicine, DR-16, White
Plains, New York) at paper speeds of 100 and 200
From the Section of Cardiology, Department of Medicine,
Abraham Lincoln School of Medicine and the University of
Illinois College of Medicine, and the West Side Veterans
Administration Hospital, Chicago, Illinois.
Supported in part by NIH contract 71-2478 under the
Myocardial Infarction Program and West Side Veterans
Administration Hospital BIS funds.
Address for reprints: Kenneth M. Rosen, M.D., University
of Illinois Hospital, P. 0. Box 6998, Chicago, Illinois
60680.
Received May 4, 1973; revision accepted for publication
August 30, 1973.
32
Circulaiiou, Volume XLlX, January 1974
CYCLE LENGTH AND CARDIAC REFRACTORY PERIODS
33
Table 1
Summary of Clinical Data, Electrocardiologic Data and Control Conduction Intervals for 24 Study Patients
Downloaded from http://circ.ahajournals.org/ by guest on April 30, 2017
Patient
number
Age
(years)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
67
35
19
42
54
26
13;
52
33
15
67
19
38
35
13
13
16
17
18
19
20
40
2'1
22
23
24
56
24
23
77
48
19
72
47
Sex
M
M
M
F
M
m
M
M
F
M
M
M
m
F
M
M
F
M
M
M
F
M
M
F
Cardiovascular
diagnosis
HHD
HHD
No HI)
ASHD
ASHD
JIHD
ASD secundum
ASHD
R HD
No HD
PMI)
ASD) secundtum
No HD
ASHD
No HD
ASHD
Cale. peric.
PDA
Coarct.
HHI)
No HD
No HD
ASHD
RHD
Sinus rate QRS duration
(beats/min)
(sec)
90
74
75
58
103
96
94
72
78
65
0.09
0.09
0.08
0.09
35
78
85
110
92
87
84
81
86
64
73
75
5a6
93
0.08
0.10
0.08
0.08
0.08
0.10
0.09
0.10
0.08
0.08
0.06
0.06
0.07
0.09
0.09
0.09
0.09
0.07
0.09
0.08
Mean frontal
QRS axis
(degrees)
-45
+ 5
+30
+20
+20
+60
+80
+30
+60
+60
-20
+100
0
-15
+60
+40
+60
+45)
+20
-10
+60
+60
+10
+50
ECG
diagnosis
LVH
ST-T
WNL
ST-T
ST-T
LVH
rr' in V1
ST-T
LVH
WNL
LVH
rr' in V1
WNL
WNL
ST-T
WNL
ST-T
WNL
LVH
ST-T
WNL
WNL
ST-T
WNL
P-A
(msec)
A-l-
(msec)
20
65
53
1iO
19
40
15
20
20
100
92
90
130
6)
100
86
71
90
124
95
70
73
104
35
33
25
40
25
15
28
28
21
35
27
19
15
21
37
25
32
H-V
(msec)
35
40
36
34
53
350
33
45
3.3
48
30
43
30
40
43
28
1]13
32
91
37
31
38
34
48
103
83
90
76
80
100
43
40
Abbreviations: P-A = interval between the beginning of the P wave and the atrial electrogram as recorded by the His bundle
catheter; A-H = interval between the atrial electrogram and the His deflection; H-V = interval between the His bundle electrogram and initiation of ventricular depolarization; HHD = hypertensive heart disease; HD = heart disease; ASHD = arteriosclerotic heart disease; RHD = rheumatic heart disease; PDA = patent ductus arteriosus; ASD = atrial septal defect; PMD
= primary myocardial disease; Coarct. = coarctation of the aorta; Calc. peric. = calcific pericarditis; WNL = within normal
limits; LVH = left ventricular hypertrophy; ST-T = nonspecific ST and T wave changes.
mm/ sec. Stimuli
were approximately twice diastolic
threshold, 2 msec in duration, and delivered by a
programmable digital stimulator (manufactured by M.
Bloom, Philadelphia, Pa.).
Refractory periods were measured with the technique
of extra stimulus. The extra stimulus (S2) was
introduced after every tenth driven (S,) or spontaneous
beat. S1-S2 intervals were decreased in 10-20 msec
decrements in successive test cycles.5 Refractory
periods were first determined during either sinus
rhythm or at the slowest paced rate producing stable
atrial capture. All patients had refractory periods
determined at two or more cycle lengths. To examine
the effect of cycle length on refractory periods, slopes
were calculated by the least squares method for
individual patients. Mean slopes (± SEM) were then
calculated for refractory periods of the atria, A-V node,
and His-Purkinje system. The term "significantly" was
defined as a change in refractory period, statistically
different from no change (zero slope). The relation
between A-V nodal conduction time (A-H) and
effective refractory period was analyzed using the
correlation coefficient.
Atrial and A-V nodal refractory periods were also
Circulation, Volume XLIX, January 1974
analyzed by computing means and ranges for three
absolute ranges of cycle length. These were 850 to 600
msec (heart rate of 70 to 100 beats/min), 599 to 460
msec (101 to 130 beats/min), and 459 to 330 msec
(131 to 180 beats/min).
A-H and H-V intervals were measured as previously
described.5 A1, H1, and V1 represent the atrial, His
bundle, and ventricular electrograms of either spontaneous or driven beats. A2, H2, and V2 represent the
atrial, His bundle, and ventricular electrograms in
response to the extra stimulus (S2).
The atrial effective refractory period (ERP) was the
longest S1-S2 interval in which atrial capture failed to
occur. At times the coupling interval of the test
stimulus was too long to determine the ERP. When this
occurred, the atrial ERP was designated as being less
than the shortest S1-S2 tested. Atrial functional
refractory period (FRP) was the shortest attainable
propagated A1-A2 interval.
The A-V nodal ERP was the longest A1-A2 interval
which did not propagate to the His bundle. A-V nodal
FRP was the shortest propagated Hr-H2 interval.
The ERP of the His-Purkinje system was the longest
H1-H2 interval in which conduction to the ventricles
DENES ET AL.
34
W
Atr'i um
0350
400 F
At r urm
E
6
° 350
(D
°£300
0
0a
° 300
,o
U
o 250
W:a 250 I-_
Si
CL
150
Number of potients 11
Mean slope 4.1 29
D .045
S.E.M. .014
0
2 200
=
c
o f pa tients 11
~~~~~~~~No.
Mean slope +155
S. D. .06
S E.M. 062
L
400
500
700
600
800
Cycle length (msec)
900
u
~~~~S.
200 F
a
400
1000
500
700
800
600
Cvele lenath (msec)
900
1000
Downloaded from http://circ.ahajournals.org/ by guest on April 30, 2017
Figure 1
Left) The atrial effective refractory period as a function of cycle length in 11 patients. Right) The atrial
functional refractory period as a function of cycle length in 11 patients. Each patient is represented as
a series of connected dots.
failed to occur. This is identical to the ERP of the
ventricular specialized conduction system as defined by
Wit et al.5 The relative refractory period (RRP) of the
His-Purkinje system was defined as the longest H1-H2
interval at which the H2-V2 interval becomes longer
than HV1, interval of spontaneous or driven beats.
Prolongation of H2-V2 could reflect conduction delays in
the His bundle distal to the His bundle recording site
and/or delays in both bundle branches.
The refractory period of a bundle branch was
considered the longest H1-H2 interval producing the
appropriate electrocardiographic pattemn of complete
bundle branch block. This refractory period could be
either relative, with the critical degree of bundle branch
delay necessary to produce a pattern of complete
bundle branch block, or effective, with total failure of
conduction in that bundle branch.
All determinations could not be obtained in all
patients or at every cycle length studied.
Results
Effect of Cycle Length on Refractory Periods
Atrium. Atrial ERP was successfully measured at
one or more cycle lengths in 23 patients (table 2).
In patient nine, the extra stimulus was not brought
550
. 450-
A V Node
E0
Va 400
AV Node
Number of patients 14
Mean slope - .177
S D .145
S. E.M. .040
No. of patients 15
Mean slope +.126
S D. .17
S.E.M. .045
en
E 500
'V
10
<, 450
a-
>, 350
a
o 400
0
U
0
,, 300
Si
° 350 l
cc
0
00250-
c
WU
U-
400
500
600
700
800
Cycle length ( msec)
900
1000
L
300,
400
1
1
500
600
-1~
-
700
800
-
9
900
000
1000
Cycle length (msec)
Figure 2
Left) The A-V nodal effective refractory period as a function of cycle length in 14 patients. Right) The
A-V nodal functional refractory period as a function of length in 15 patients. The crossed dots
represent the atriad functional refractory period in those instances where this exceeded the A-V nodal
effective refractory period. The actual value of the A-V nodal ERP can only be less than the atrial
FRP at these points.
Circulation, Volume XLIX, January 1974
CYCLE LENGTH AND CARDIAC REFRACTORY PERIODS
35
550r
c)
E
500r-
a)
His Purkinje System
0
-0
0.
0
Bundle Branches
- ~Right BB
. .Left BB
500F
-o0
450-
4500-
a)
4001
0
E,
0
a
0
3501
,< .
0
300'L
400
Number ofpetients 6
~~~Meon s lope + .27
S. D. .109
S. E. M. .044
1
500
600
700
Cycle length
4001-
cr-
Number of patients 7
350-
Mean slope + .360
S.D.
300
L
S. E. M. .065
IL4
800
900
(msec)
.173
L
1000
500
400
600
700
Cycle length
800
900
(m sec)
10Z00
Downloaded from http://circ.ahajournals.org/ by guest on April 30, 2017
Figure 3
Left) Relative refractory period of the His-Purkinje system as a function of cycle length in six patients.
Right) Refractory period of the bundle branches as a function of cycle length in seven patients. The
crossed dots represent the A-V nodal functional refractory period in those instances where this exceeded the His-Purkinje system relative refractory period.
in close enough to
measure atrial ERP or FRP at
cycle length. For purposes of analysis, slopes of
the relationship of atrial ERP to cycle length were
calculated for patients in whom four or more
recordings over a cycle length range not less than
200 msec (11 patients) were made. The mean
slope SEM was +0.155 0.020 msec (figs. 1 and
4). Thus, atrial ERP decreased significantly as cycle
length was shortened. The means and ranges of
atrial ERP for all 23 patients are given in table 3.
Atrial FRP was measured in 23 patients (table
2). Slopes were calculated for all patients in whom
four or more recordings over a cycle length range
not less than 200 msec (11 patients) were made.
The mean slope SEM was +0.129 + 0.014 msec
(figs. 1 and 4). Thus, atrial FRP decreased
significantly as cycle length was shortened. The
means and ranges for all 23 patients are given in
table 3.
A-V node. A-V node ERP could be determined in
18 patients (table 2). Slopes were calculated for all
patients in whom three or more determinations over
a cycle length range not less than 200 msec (14
patients) were made. The values at which atrial
FRP exceeded the A-V nodal ERP at the initial
(longest) cycle length were also computed (patients 8, 10, and 19) for calculation of the slopes,
since A-V nodal ERP could only be less than the
values indicated. The mean slope-+ SEM was
-0.177 + 0.040 (figs. 2 and 4). Thus, A-V nodal ERP
any
Circulation, Volume XLIX, January 1974
< -02
-04
-E
E:mean
-06
ERF
FRP
ATRIUM
ERP
FRP
RRP
RP
A-V NODE
HPS
BB.
Figure 4
The effect of change in cycle length on the change in refractory periods of the atrium, A-V node, and His-Purkinje
system. Each point represents the mean slope of change in
refractory period related to change in cycle length for
individual patients. A positive value indicates that as cycle
length decreases refractory periods decrease. A negative
value indicates that as cycle length decreases refractory
period increases. A zero value indicates no change in refractory period despite change in cycle length. ARP = change in
refractory period (msec); ACL = change in cycle length
(msec); ERP = effective refractory period; FRP = functional
refractory period; RRP = relative refractory period; RP.=
refractory period; HPS = His-Purkinje system; BB = bundle
branches. Mean SEM are indicated.
36
DENES ET AL.
Table 2
Electrophysiological Data for 24 Patients*
Patient
CL
A ERP
A FRP
1
630
;)20
430
240
210
200
640
480
667
043
462
85)0
AVN ERP
AVN FRP
285
265
245
<28.5
< 265
<245
43 15
55
34,5
325
65)
65
270
305
< 305
< 3153)
345
390
430
435
120
150
265
265
<24.5
290
285
<270
300
335
320
440
500
445)
100
110
120
230
225
235
285
265
29,5
28 5
280
315
420
415
415)
105
125
165
390
360
190
180
180
190
265
24 5
255
2.50
< 265
<245
<25 5
t
335
330
330
90
100
100
6
600
450
400
<270
190
195
<270
225
25)0
275
275)
275
33i5
325
-
65
105
105
7
600
445
195
2
3
4
600
490
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a 70
450
8t
9
10
210
215
280
325
415
41.5
80
200
-790
580
470
420
190
250
225)
200
200
265
235
225
235
< 265
310
75
100
110
110
667
4;5
<210
<245
<215
<245
350
375
360
350
430
7615
560
290
290
270
260
310
410
480
445
11
12
A-H
710
580
480
285
305
320
405
490
520
350
370
t
505
80
110
120
400
255
450
475
475
100
120
160
25)0
270
310
3653
270
295
<4225
405
425
330
370
365
390
180
2.50
260
260
480
440
360
190
190
210
215
180
205
t
6150
530
260
260
260
290
320
465
435
400
100
140
160
14
430
480
390
210
230
200
190
200
223
225
<2225
<225
<290
<305
70
100
1.5
480
<263
190
<26.3)
200
270
400
3,50
315
100
100
613)
52(0
445
215)
230
203
440
423
405
115
140
140
375
205
690
o60
510
13
16
230
22,5
275
300
280
275
265)
495
510
475
470
HPSRRP
355R
<330
355
<330
470R
395
<360
425
380
<360
315R
<305
-
115
128
<310
335
310
290
270
280
<42 5
460
BB RP
130
180
220
280
t-
250
340
3350
365
t
-
Circulaiion, Volume XLIX, January 1974
CYCLE LENGTH AND CARDIAC REFRACTORY PERIODS
AVN ERP
Patient
CL
A ERP
A FRP
17
675
560
510
470
444
360
745
690
565
480
400
380
755
670
522
720
580
485
420
380
870
650
550
450
720
680
1000
640
480
420
620
560
470
353
230
280
310
230
230
195
300
260
240
240
230
300
275
280
275
275
240
230
195
195
365
365
340
330
330
310
295
260
260
200
190
390
340
305
295
250
210
210
195
360
405
420
18
19
Downloaded from http://circ.ahajournals.org/ by guest on April 30, 2017
20
21
22
23
24
190
180
220
220
210
205
205
165
150
160
160
34,5
335
290
285
265
230
200
185
190
190
170
360
300
250
230
220
190
180
170
37
AVN FRP
A-H
470
460
470
470
160
195
230
BB RP
HPS RRP
425L
<390
425
<390
460R
405
355
340
460
390
365
350
120
tt300
310
320
330
325
330
<230
270
265
<365
<365
<340
<330
<330
310
295
320
310
<200
<190
<390
<340
<305
<295
250
280
290
410
390
380
375
370
365
405
390
360
<395
<365
<350
<335
<335
385
360
330
335
425
370
<440
<390
<365
<380
405
400
390
95
100
105
130
130
140
105
110
125
100
115
145
155
150
80
120
135
125
100
115
95
135
155
460R
380
< 330
<335
410
370
<330
520L
400
<365
455
400
<365
<335
180
105
125
150
t
*All values are expressed in msec.
tCL at which type I second degree block proximal to H was present.
tThe ERP of the HPS was 395 msec at the CL of 790 msec in this patient. The FRP of the A-V node exceeded the ERP of the HPS at a shorter CL.
Abbreviations: CL = cycle length; A ERP = atrial effective refractory period; A FRP = atrial functional
refractory period; AVN ERP = A-V nodal effective refractory period; AVN FRP = A-V nodal ftnctional
refractory period; A-H = interval between the atrial electrogram and the His deflection recorded by the His
bundle catheter; BB RP = Bundle branch refractory period; Ri = indicates right bundle; L indicates left
bundle; anid HPS RRP = His-Purkinje System relative refractory period.
lengthened significantly as cycle length was shortened. The means and ranges for all 18 patients are
given in table 3.
A-V nodal FRP could be measured in 21 patients
(table 2). Slopes were calculated for all patients in
whom three or more determinations over a cycle
length range of more than 200 msec (15 patients)
were made. The mean slope ± SEM was +0.126 ±
0.045 msec (figs. 2 and 4). Thus, A-V nodal FRP
Circulation, Volume XLIX, January 1974
decreased as cycle length was shortened. Means
and ranges for all 21 patients are given in table 3.
A-V nodal conduction time (A,-H,) lengthened
in all patients as cycle length was shortened. The
relationship of A-V nodal conduction time to
effective refractory period was examined by plotting A,-H1 intervals against the ERP of the A-V
node for each patient at all cycle lengths in which
both were measured. A statistically significant
DENES ET AL.
38
Table 3
The Effective and Functional Refractory Period at Three Cycle Length Ranges for the Atrium
and the A-V Node*
599-460
101-130
459-380
131-180
235 (150-360)
25
19
278 (190-390)
23
19
225 (160-335)
29
18
267 (195-365)
29
18
201 (165-285)
23
16
248 (195-330)
23
16
303 (250-365)
16
15
421 (350-495)
23
18
340 (265-425)
29
16
419 (330-520)
31
18
307 (275-365)
9
8
351 (313-415)
11
10
CL
HR
=
=
850-600
70-100
ATRIUTM
ERP mean (range)
Number of observations
Number of patients
FRP mean (range)
Number of observations
Number of patients
A-V NODE
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ERP mean (range)
Number of observations
Number of patients
FRP mean (range)
Number of observations
Number of patients
*All values are expressed in msec.
Abbreviations: HR = heart rate, beats/mim; CL = cycle length in msec; ERP = effective refractory period;
FRP = functional refractory period.
correlation was found with an (r) value of +0.65
(fig. 5). No similar relationship was found between
A,-Hi and A-V nodal FRP.
His-Purkinfe system. The RRP of the HisPurkinje system could be measured in six patients
(table 2). Slopes were calculated for all six patients.
The values obtained at the longest cycle length in
which A-V nodal FRP exceeded the RRP of the HisAH vs AVN-ERP
r =+.646
300
SEE=34
D=< 001
0
0
250
0
@ 200
1)
E
*/
0
<
5
.
0
0
,
0*
0
Relationship between Refractory Periods
of Different Cardiac Tissues
100
e* @*
-:
0
*
7J
0
200
300
350
250
AVN- ERP( msec)
Purkinje system were also computed from the
recordings of all patients for calculation of the
slopes, since the RRP of the His-Purkinje system
could only be less than the values indicated. The
mean slope ± SEM was +0.270 ± 0.044 (figs. 3 and
4). Thus, the RRP of the His-Purkinje system
shortened significantly as cycle length was decreased.
Bundle branch refractory periods could be
measured in seven patients (left bundle branch in
two and right bundle branch in five, table 2).
Slopes were calculated as described for the HisPurkinje system for these patients. The mean
slope + SEM was +0.36 ± 0.065 (figs. 3 and 4).
Thus, bundle branch refractory periods decreased
significantly as cycle length was shortened.
The ERP of the His-Purkinje system could be
measured in only one patient (patient 8) and was
395 msec at a cycle length of 790 msec (table 2).
400
450
Figure 5
The relationship of A-V nodal conduction times (A-H) and
effective refractory periods. The A-V nodal conduction times
(A-H) of driven stimuli are plotted against A-V nodal effective refractory periods at the driven cycle length (AVNERP). Values of 54 cycle lengths from 18 patients are
plotted.
Atrial FRP vs A-V Nodal ERP. The A-V nodal
effective refractory period could not be measured in
six patients because the atrial FRP was longer at all
cycle lengths. In eight of the remaining 18 patients,
the atrial FRP was equal to or exceeded the A-V
nodal ERP at the longest basic cycle length tested.
In all eight cases this cycle length was greater than
600 msec.
A-V Nodal FRP vs His-Purkinje System Refractory Periods. The RRP of the His-Purkinje system
Circulation, Volume XLIX, January 1974
CYCLE LENGTH AND CARDIAC REFRACTORY PERIODS
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exceeded the A-V nodal FRP in five out of ten
determinations (50%) at basic cycle lengths greater
than 700 msee, in five out of 36 determinations
(14%) between cycle lengths of 700 and 500 msec,
and in two out of 25 determinations (7%) at cycle
lengths less than 500 msec.
The RP of the bundle branches exceeded the A-V
nodal FRP in five out of ten determinations (50%)
at basic cycle lengths greater than 700 msec, in five
out of 36 determinations (14%) between 500 and
700 msec and in three out of 26 determinations
(12%) at cycle lengths less than 500 msec.
These relationships can be better visualized by
examining the values from recording a typical
patient. Values from patient 8 are shown in figure 6.
At a cycle length of 790 msec, the shortest attainable
interval between two atrial impulses that traverse
the A-V node (H,-H2) was 350 msec (A-V nodal
FRP). Impulses that propagated through the node
J.G. REFRACTORY PERIODS
450
RBB
-,' ARBB
h
U
0
0
X
LUJ
350
AVFRP
0-
AVERP
o
300
U
`
cc
250
AFRP
20C _ AERP,.
_l400
600
700
500
LENGTH
CYCLE
(msec)
800
Figure 6
Refractory periods of the atrium, A-V node, and right
bundle branch as a function of cycle length in one typical
patient (patient 8).
RBB =refractory period of the right bundle branch
represented by open triangles and connected with interrupted lines. AVFRP= A-V nodal functional refractory
period represented by open circles and connected with full
lines. AVERP-A-V nodal effective refractory period represented by open circles and connected with interrupted
lines. AFRP =atrial functional refractory period represented by closed circles and connected with full lines.
AERP=atrial effective refractory period represented by
closed circles and connected with interrupted lines.
Circulation, Volume XLIX, January 1974
39
with an H,-H2 between 350 and 470 msec produced
right bundle branch block pattern. At a cycle length
of 580 msec, the A-V nodal FRP was 375 msec, and
impulses with an H1-H. interval between 375 and
395 produced right bundle branch block. At a basic
cycle length of 470 msec, the A-V nodal FRP
exceeded the right bundle branch refractory period
and functional right bundle branch block was not
noted. At the longest cycle length (790 msec) the
atrial FRP exceeded the A-V nodal ERP. Since
these RP diverge at shorter cycle lengths, A-V nodal
ERP exceeded atrial FRP at these cycle lengths.
Discussion
Effect of Cycle Length on Refractory Periods
It has been demonstrated with microelectrode
techniques in isolated cardiac tissues that action
potential durations and refractory periods of atrial
muscle, ventricular muscle, and His-Purkinje cells
decrease with shortening of cycle length.' The A-V
nodal cell differs in that recovery of excitability is
delayed beyond complete repolarization. At higher
driving rates, this gap between complete repolarization and recovery of excitability increases further.6
Mendez et al. examined the effects of changes in
cycle length on the functional refractory periods of
tissues in denervated canine hearts. They demonstrated that the functional refractory periods of the
atria, ventricles, and A-V node were a curvilinear
function of cycle length and shortened as cycle
lengths decreased.2 Although our findings in man
showed similar changes, the changes in refractory
periods produced by changes in cycle length could
not be described in terms of a single mathematical
function. In this respect our results differ from those
obtained in canine hearts. This difference can
perhaps be explained by the fact that autonomic
nervous systems were intact in our patients. In
addition, the cycle length ranges we could study
were limited since heart rates could not be slower
than spontaneous sinus rhythm, or faster than the
rate at which A-V nodal Wenckebach periods were
observed. Atrial ERP and FRP had positive mean
slopes when related to cycle length. The A-V nodal
ERP had a negative mean slope when related to
cycle length. In the recordings for all except one
patient A-V nodal ERP increased when cycle length
was decreased. In contrast, the FRP of the A-V
node had a positive mean slope, although there vas
a wide scatter of individual patients (fig. 4).
Refractory periods in the His-Purkinje system
showed the greatest decrease as eyele length
shortened.
DENES ET AL.
40
Relationship between Refractory Periods
of the Cardiac Tissues
The FRP of an excitable tissue at a given cycle
length is the shortest attainable time interval
between two impulses traversing that tissue, measured at a point distal to the stimulation site.2 The
ERP of a tissue is the longest time interval between
two impulses where the second fails to traverse it. If
the FRP of the atrium is longer than the ERP of the
A-V node, the A-V nodal ERP cannot be measured,
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since the atrium limits A-V conduction. The
relationship between change in atrial FRP and A-V
nodal ERP in response to variation in cycle length
showed that the atrium might limit the determination of A-V nodal ERP at long cycle lengths, but
this is less likely to occur at short cycle lengths (fig.
6 and table 2). A similar relationship between the
A-V nodal FRP and the RP of the His-Purkinje
system is possible. In long cycle lengths, the
refractory period of the right bundle branch is
frequently longer than the FRP of the A-V node.
This allows a premature beat to be conducted with
an 1-H2 interval shorter than the right bundle
branch refractory period, producing functional
right bundle branch block (aberrant conduction).
At shorter cycle lengths the right bundle branch
refractory period and the A-V nodal FRP converge,
and aberrant conduction cannot occur. Aberrant
conduction of a premature supraventricular beat is
thus more likely during sinus bradycardia or when
preceding R-R intervals are lengthened.
Measurement of His-Purkinje system refractory
periods with the atrial extra stimulus method is
dependent upon three factors: 1) the A-V nodal
FRP, 2) cycle length, and 3) the RP of the HisPurkinje system. In this study, those patients in
whom determinations of His-Purkinje system refractory period could be obtained tended to have
shorter A-V nodal FRP than those patients in whom
His-Purkinje system refractory period could not be
measured. Most determinations of His-Purkinje
system refractory periods were obtained at cycle
lengths greater than 600 msec. In two patients (5
and 14), both with sinus tachycardia, initial
refractory period measurements could be obtained
only at cycle lengths less than 600 msec.
Moe et al. noted a similar relationship in
denervated canine hearts.7 In his study, bundle
branch refractory periods exceeded A-V nodal
refractory periods at longer cycle lengths. Epinephrine reduced the refractory periods of the A-V
node, His bundle, and bundle branches. However,
the epinephrine effects were more pronounced in
the A-V node than in the bundle branches. This
might explain why bundle branch refractory
periods could be obtained at cycle lengths less than
600 msec in the two patients with sinus tachycardia
who were probably not under basal conditions
during the period of the study.
Conduction Time and Refractory Periods
A-V nodal conduction time (A-H interval)
increases as cycle length shortens. This increase has
been attributed to the low amplitude of the A-V
nodal action potential, the low A-V nodal resting
membrane potential, and the decreased rate of
depolarization of the A-V nodal cells in response to
shortening of cycle length.' Merideth et al.6 have
shown in rabbit hearts that the frequency-related
depression of A-V nodal conductivity is associated
with both an increase in diastolic threshold and
delays between full repolarization and recovery of
excitability. Van Capelle et al.,8 working with rat
heart, suggested that A-V nodal conduction time
(A-H) could determine A-V nodal refractoriness for
a subsequent impulse. Our study suggests that A-H
interval might be a partial determinant of A-V
nodal ERP. No such relationship was found for A-H
and A-V nodal FRP.
Experimental Limitations
Several limitations should be considered in the
interpretation of our results. First, most of the
patients had evidence of organic heart disease. It is
possible that cycle length-refractory period relationships might have been slightly different in a group
of patients without heart disease. However, findings
in our six normal patients were similar to the
findings in the 18 patients with heart disease.
Second, since autonomic nervous system influences
were intact, reflex responses to paced changes in
cycle length could have influenced our results.
Third, the results of this study probably are not
applicable to changes in refractory periods induced
by spontaneous changes in heart rates, as occurring
with exercise or change in posture. Spontaneous
changes in rate are generally mediated by changes
in sympathetic and/or parasympathetic tone, which
have direct effects on conduction. Similarly, the
changes described in this study would not apply to
cycle length changes induced by drugs with direct
effects on the conduction system.
This study therefore describes changes in refractory periods related to paced changes in cycle
length and are of value in understanding cardiac
electrophysiological responses in man. These results
Circulation, Volume XLIX, January 1974
CYCLE LENGTH AND CARDIAC REFRACTORY PERIODS
may be directly applicable to changes in rate not
mediated by the autonomic nervous system, as
occur in some paroxysmal arrhythmias or in A-V
block.
References
1. HOFFMAN BC, CRANEFIELD PF: Electrophysiology of
the heart. New York, McCraw-Hill Book Company,
1960
2. MENDEZ C, GAUHZIT CC, MOE GK: Influence of cycle
length upon refractory periods of auricles, ventricles
and A-V node in the dog. Am J Physiol 184: 287,
1956
3. DHINGRA RC, ROSEN KM, RAMMTOOLA SH: Normal
conduction intervals and responses in 61 patients
using His bundle recording and atrial pacing. Chest
64: 55, 1973
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Circulation, Volume XLIX, January 1974
41
4. SCHERLAG BJ, LAU SH, HELFANT RM, STEIN E,
BERKOWITZ WD, DAMATO AN: Catheter technique
for recording His bundle activity in man. Circulation
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5. WIT AL, WEISS MB, BERKOWITZ WD, ROSEN KM,
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1970
6. MERIDETH J, MENDEZ C, MUELLER WJ, CORDON GK:
Electrical excitability of atrioventricular nodal cells.
Circ Res 23: 69, 1968
7. MOE GK, MENDEZ C, HAN J: Aberrant A-V impulse
propagation in the dog heart: A study of functional
bundle branch block. Circ Res 15: 261, 1955
8. VAN
CAPELLE
FJL,
DUPERRON JC,
DUPBER
D:
Atrioventricular conduction in isolated rat heart. Am
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The Effects of Cycle Length on Cardiac Refractory Periods in Man
PABLO DENES, DELON WU, RAMESH DHINGRA, RAYMOND J. PIETRAS and
KENNETH M. ROSEN
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Circulation. 1974;49:32-41
doi: 10.1161/01.CIR.49.1.32
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