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Ventricular endocardial potentials after experimental coronary artery occlusion in dogs
Ventricular endecardial potentials coronary artery occlusion in dogs Kanu Chatterjee, M.B., B.S., M.R.C.P.(Lono?.), William Rouse, B.Sc., Ph.D. London and Cheshire, England
L
ow right ventricular endocardial potentials (RVECP) in patients with acute myocardial infarction have been previously reported, 1-3 but the mechanisms remain unexplained. It is not known, for example, whether the low ECP is due to the electrode being in contact with ischemic endocardium or not. Furthermore, the behavior of left ventricular endocardial potential (LVECP) and its relation to RVECP, following coronary artery occlusion, are also not known. In the clinical study, an apparent relationship was noted between the degree of fall of RVECP and the severity of clinical heart failure, but no hemodynamic measurements were performed to verify this clinical impression. The present study was designed to investigate, in dogs, the behavior of both right and left ventricular endocardial potentials and their relation to hemodynamic alterations following experimental complete coronary artery occlusion.
Methods Nine beagle dogs, 9.5 to 13.2 kilograms in body weight, were anesthetized with intravenous pentobarbitone (30 mg. per kilo-
after
experimental
M.R.C.P.(Edin.)*
gram) and their respiration was maintained mechanically by a positive pressure respirator (Palmer Starling Respirator). The chest was opened by midsternotomy in one dog and by left thoracotomy through the fifth intercostal space in eight dogs. The heart was exposed by excising the pericardium. For recording endo- and epicardial potentials, “hook” electrodes made of Nichrome wires (8/1,000 inch diameter) were used. The whole length of the electrodes, except at the tip in the case of endocardial, and at the “angle of the hook” in the case of epicardial electrodes, were insulated with Diamel varnish. The epicardial electrodes were attached to the superficial layers of the epicardium directly. The endocardial electrodes were introduced into the ventricular cavity through a No. 1 hypodermic needle and then gently withdrawn until the electrograms recorded showed characteristic ventricular intracavitary configuration with ST elevation contact pattern.4 In all experiments, unipolar potentials were recorded and, in two experiments, in addition, bipolar potentials were also recorded simultaneously from the same sites. The approximate distance between
From
the Cardiac Department. Brompton Hospital. London. S.W.3, and the Pharmaceutical Macckslield, Cheshire, England. Received for publication Nov. 18. 1970. Reprint requests to: Dr. Kanu Chatterjee, Department of Cardiology, CedarsSinai Medical calif. 90054. *Present address: Dept. of Cardiology. Cedars-Sinai Medical Center, Los Angeles, Calif.
352
American
Heart
Journal
September, 1971
Division.
Center.
I.C.I.
Los
Ltd.,
Angeles.
Vol. 82, No. 3, pp. 352-361
Volrrme 82
Number
Ventricular
3
the bipolar leads was l/l,OOOth inch. Needle electrodes were used for recording standard Lead II electrocardiograms (ECG). RVECPs were recorded from the inferior wall, near the apex. LVECPs were recorded from two sites: (1) the anterior wall in the left anterior descending artery territory (LVECP Ant.), and (2) the inferior wall in the left circumflex artery territory (LVECP Inf.). Left ventricular epicardial potentials (LVEPP) were recorded from the anterior surface in the anterior descending artery territory (LVEPP Ant.) and from the inferior surface in the left circumflex territory (LVEPP Inf.). No right ventricular epicardial potentials (RVEPP) were recorded. A cathetertipped micromanometer” was introduced into the cavity of the left ventricle through its apex and the first derivative of left ventricular pressure pulse (LV dp/dt) was determined by electronic differentiation. Aortic pressure was measured by left carotid artery cannulation. All parameters were recorded simultaneously on an eightchannel tape recorder (Precision Instruments) and permanent records were subsequently obtained on an eight-channel paper recorder (Minograph 81). The coronary artery to be ligated was first dissected and isolated near its origin and a cotton thread was placed loosely around it. After a control period of observation for 30 minutes, the artery was ligated and observations were continued for at least 60 minutes. At the end of the experiments, the animals were killed and the hearts were dissected to verify the positions of the endo- and epicardial electrodes. To delineate the ischemic areas, 15 to 20 C.C. of Coomassie Blue dye were injected at the root of the aorta in six dogs. After the animals had been killed and the hearts had been dissected, well-perfused areas were bright blue and the clearly unperfused areas remained gray. Thus the ischemic (nondyed) and the nonischemic (dyed) areas could be identified on both the epicardial and endocardial surfaces of the ventricles. Histological examinations were not performed. The calibration voltage for the measure*S. E. Laboratories,
Ltd.,
London,
Ew&nd.
endocardial
potentials
353
ment of the potentials was chosen according to the amplitude of the potential. The potential was defined as the total deflection of the QRS (without the ST) and the measurement taken was the average of ten complexes (ventricular premature beats were excluded), The control measurements of the potentials, LV dp/dt, and mean aortic pressure (PAO) at 30 minutes before the ligation of the coronary arteries were regarded as 100 per cent and the changes at subsequent observations, both immediately before (0 minute) and after ligation (t 10, 20, 30, 40, 50, and 60 minutes), were expressed as the percentage of the control values. Results In six of the nine dogs the left circumflex artery (LCA) was ligated; in two dogs the left main coronary artery (LMCA) was ligated: in one dog the left anterior descending (LAD) artery was ligated. In eight dogs the postocclusion changes were recorded at ten-minute intervals up to 60 minutes; in one animal ventricular fibrillation occurred 15 minutes after ligation of the LMCA, and in this dog the postocclusion changes were recorded only at ten minutes. A typical example of changes in LVECP and LVEPP following occlusion of a coronary artery is shown in Fig. 1. The percentage changes in the mean values of the potentials, LV dp/dt, and aortic pressures, both before and after ligation of the coronary arteries, are shown in Table I and Fig. 2. Postocclusion changes in individual experiments are shown in Fig. 3. The pre- and postocclusion potentials (in millivolts) are summarized in Table II. Endocardial potentials. LVECP Ant. fell in all nine dogs following coronary artery occlusion (Fig. 3, a). LVECP Inf., recorded in six dogs, fell in four and remained unchanged in two (Fig. 3, c). RVECP, recorded in seven dogs, fell significantly in four and remained unchanged in three (Fig. 3, e). The mean postocclusion ECP remained lower than the control values throughout the period of observation (Table I). The fall in ECP, when it occurred, was not related to the coronary artery ligated (Table II).
354
Chatterjee and Rouse
Fig. 1. Simultaneously recorded endo- and epicardial potentials from the anterior and inferior walls of the left ventricle, both before and after circumflex artery occlusion. Both LVECP Ant. and LVECP Inf. fell following occlusion. Transient rise in epicardial potentials with appearance of the injury pattern followed by gradual fall is also shown.
LVECP Ant. was recorded in all six hearts that were examined by injection of dye to delineate ischemic areas. LVECP Inf. and RVECP were recorded only in five such hearts. Fall in LVECP Ant. was observed whether the electrodes were in ischemic (three hearts) or in nonischemic areas (three hearts). The endocardial electrodes for LVECP Inf. were in ischemic areas in four (in three a fall in LVECP Inf. occurred and in one no change was observed) and in nonischemic areas in one heart (no change in LVECP Inf. occurred). The electrodes for RVECP were in ischemic areas in two hearts, but only in one of these did a fall in RVECP occur. In the remaining three hearts the electrodes
were in nonischemic areas and in two of these RVECP fell. Bipolar potentials. Bipolar and unipolar potentials were recorded simultaneously in two dogs from the same sites. Although the bipolar potentials were smaller in amplitude than unipolar potentials, the postocclusion changes were similar (Fig. 4). Epicardial potentials. LVEPP Ant. were recorded in nine dogs and LVEPP Inf. in six. After ligation of the coronary artery the changes in epicardial potentials were variable. In most dogs there was an initial increase in epicardial potentials with the appearance of the injury pattern (monophasic potential and marked ST elevation), followed by a gradual fall (Figs. 1 and 2). At
123 * 66.0 0.20 < P < 0.25
105 k 42.0 0.40 < P < 0.50
644.0 zk 14.8 P < 0.001
61.6 + 14.0 P < 0.001
61.6 Ik 14.5 P < 0.001
+40
-i-50
+60
*Values at 30 minutes before are also shown, along with
122 rt 76.0 0.25 < P < 0.30
63.1 + 19.3 P < 0.001
-l-30
coronary standard
(
artery occlusion deviation.
99.7 f 26.6 0.80 < P < 0.90
123 + 29.0 0.01 < P < 0.02
110 + 29.0 0.10 < P < 0.20
100 94.0 * 14.0
65.8 + 16.0 P < 0.001
100 + 3.7
4-20
101
LVEPP
72.6 + 13.3 P < 0.001
0
j
+10
-30
(Ant.)
(I?$)
100 99.5 f 4.6
LVECP
and PA0
were
regarded
1
(I$.)
cent
and
( 100 t 5.8
78.1 + 22.5 P = 0.02
101
RVECP
arteries*
changes
, 100 93 + 9.0
LeadII
as percentage
105 + 29.9 0.30 < P < 0.40
134 + 36 0.005 < P < 0.01
120 k 24 0.01 < P < 0.02
119 + 34 0.05 < P < 0.10
114 + 58 0.30 < P < 0.90
134 f 64 0.10 < P < 0.20
are expressed
82.5 f 29.9 0.05 < P < 0.10
72.6 + 30.2 0.025 < P < 0.05
78.8 + 21.1 0.01 < P < 0.02
82.6 + 29.1 0.05 < P < 0.10
85.6 + 24.4 0.10 < P < 0.20
the subsequent
86 + 30 0.20 < P < 0.25
92 + 40 0.50 < P < 0.60
107 f 36 0.70 < P < 0.80
111 Ik 35 0.50 < P < 0.60
111 zk 34 0.50 < P < 0.60
125 + 39.0 0.05 < P < 0.10
100 102 * 7.4
LVEPP
after ligation of coronary
as 100 per
64.3 rt 26.5 0.005 < P < 0.01
64.8 J- 25.9 0.005 < P < 0.01
69.6 f 28.6 0.025 < P < 0.05
71 f 18.7 0.001 < P < 0.005
78.5 It 18.0 0.005 < P < 0.01
87.8 + 14.1 0.05 < P < 0.10
(Ant.)
LVECP
off,
(
LV dp/dt,
Table I. Changes in potentials,
100 102.8 + 11.2
LV dp/&
values.
Statistical
66.6 rt 25.3 0.005 < P < 0.01
56 + 24.8 P < 0.001
69.5 + 21.3 0.001 < P < 0.005
68.3 + 21.7 0.001 < P < 0.005
62 i- 11.5 P < 0.001
66.5 rk 25.0 0.001 < P < 0.005
of these
/
/
100 + 10.5
significance
(P values)
86 zb 25.7 0.05 < P < 0.10 88.6 * 31.4
82.0 5 26.0 0.025 < P < 0.05
88.3 i 31.3 0.10 < P < 0.20
99 * 8.8 0.10 < P < 0.20
108
PA0 (mean)
356
-50 ’ I 0
Am Heart I. .Sc/hwber, 1971
Chutterjce und Roux
I 10
Fig. 2. Percentage tials, LV dp/dt, coronary arteries.
I I I 20 30 40 Time (minutes) changes and PA0
in mean following
I 50
I 60
values of potenligation of the
60 minutes, LVEPP Ant. was slightly increased in four dogs, slightly reduced in three, and unchanged in two dogs, as compared with control values (Table II, Fig. 3, c). Similarly, LVEPP Inf. at 60 minutes was reduced in four dogs and increased in two, as compared with control values (Table II and Fig. 3, d). The changes in epicardial potentials were not related to the coronary artery ligated. No correlation was present between postocclusion percentage change of LVEPP Ant. and LVEPP Inf. ; neither was there any correlation between changes in LVECP Ant. and LVEPP Ant. or LVECP Inf. and LVEPP Inf. In six hearts that were examined by injection of dye, the epicardial electrodes, on both the anterior and inferior walls of the left ventricle, were in mottled areas; whether the electrodes were in ischemic or nonischemic areas could not be precisely determined. Potentials in Lead II. Lead II ECG’s recorded in seven of the nine dogs showed variable changes following ligation of the coronary arteries. QRS potentials increased initially in most dogs, with the
appearance of the injury pattern (ST elevation) followed by a gradual fall of QRS potential (Fig. 2). At 60 minutes it was slightly increased in four dogs, slightly reduced in two, and unchanged in one (Table II). The changes in potentials were not related to the coronary artery ligated (Fig. 3, f). Rate of rise of LV dp/dt. The changes in LV dp/dt were recorded in seven of the nine dogs. After ligation of the coronary arteries, reduction occurred in all but one dog (Fig. 2, g). The mean postocclusion reduction was significant at all periods of observation (Table I). The correlation between postocclusion changes in LV dp/dt and in LVECP and between LV dp/dt and RVECP are shown in Fig. 5. Moderate but significant correlation was found between changes in LV dp/dt and LVECP (r = 0.568, P < 0.001) and between LV dp/dt and RVECP (r = 0.548, P < 0.001). Changes in PA0 were recorded in seven of the nine dogs; there was an initial fall in five dogs and no significant change in two following ligation of the coronary arteries (Fig. 3, h). In general the fall in PA0 was not marked and in most dogs PA0 returned almost to control level at 60 minutes after ligation of the coronary arteries. No correlation was found between the changes in PA0 and changes in LVECP or RVECP. Discussion The clinical observation that a fall in ventricular endocardial potentials may occur following acute coronary artery occlusion was confirmed in this study. In all animals, during the control period of observation, there was no change either in left or right ventricular endocardial potentials. Following ligation of the coronary arteries, LVECP Ant. fell in all animals and LVECP Inf. and RVECP in most. The fall in endocardial potential occurred soon after ligation and the values remained lower than the control values throughout the periods of observation. The present study also demonstrated that postocclusion changes in endocardial potentials recorded simultaneously from the two ventricles or from the different sites of the same ventricles may vary. In Dogs 4 (LC ligated) and 5 (LMC ligated), LVECP Ant. fell but no changes were observed in LVECP Inf. or in RVECP
Vcnlridar
Time
of occlusion
o
oOcclusion
of L. M. C. A.
*Occlusion mOcclusion
of L.C. A. of L. A. D.A.
Time
endocardial
of
OccluSiOn
potentials
3.57
Of
loo2iz u *
20
0
LVECP (Ant) 0’
LVEPP (Ant)
LVECP 04
+60 O+60 0+do Time (Minutes) (4
04
LVEPP w o-
(4
Fig. 3. Changes in individual exoeriments Lv dp/dt (gj, and mean PA0 (h).
8060.
20
0
+60
RVECP 0+iOb (4
(4 at 60 minutes
(Table II). The explanation for this difference remains obscure but it is unlikely to be due to the cancellation of the potentials at the two surfaces of the ventricle as no reciprocal relation was found between LVECP Ant. and LVECP Inf. (Fig. 6). The changes in ECP in this study could not be attributed to electrode position in relationship to ischemic or nonischemic endocardium (Fig. 7). In six hearts examined with injection of dye to delineate ischemic and nonischemic endocardium, the endocardial electrodes at the anterior wall of LV were in ischemic areas in three and in nonischemic areas in the other three, but LVECP Ant. fell in all. In two of the same six hearts, however, where LVECP Inf. and RVECP were also recorded simultaneously with LVECP Ant., no fall occurred in LVECP Inf. in one and in RVECP in the other, although the endocardial electrodes were in contact with ischemic endocardium. The explanation of this lack of change in ECP recorded from the ischemic area remains obscure. Hellerstein and Katq6 while investigating LLelectrical effects” of experimental myocardial injury in dogs, also reported in some animals no alteration in “QS complexes recorded from a subjacent electrode within the right ventricular cavity after local coagulation of a large area of the anterior
ECG Lead 2 LV dp/dt +60 0+dO Time (Minutes)
after
ligation
(f)
of the coronary
Time
Ff? 40.
. -30
. -20
Fig. 4. Changes in (open circles) and from the anterior and after ligation
PAo(mean) Ot60 (h)
cd arteries,
of occlusion of L.C.& . . . . -10 0 +lO +20 Time (minutes)
potentials
(a to!),
. . . . +30 +40 +50 +60
simultaneously recorded unipolar bipolar (closed circles) potentials wall of the left ventricle before of the left circumflex artery.
wall of the right ventricle.” Hence, although the relationship between localized myocardial ischemia or infarction and fall of ECP remains uncertain, these findings suggest that it is not due to the electrode being in contact with ischemia or infarcted endocardium or only due to loss of local potentials. It also appears that myocardial infarction, per se, may not be directly responsible for the fall in ECP. This is also supported by the clinical observation that transient fall in RVECP may occur in patients undergoing open-heart surgery under deep hypothermia2 and in some patients with acute massive pulmonary em-
IJisni 11itlrout pre\.ious c.artliorcsl~ir;ltur) disease.” The poslocclusion changes in direct epicardial potential and in potential recorded in Lead II were variable. In most experiments, immediately after coronary artery ligation and concurrent with the appearance of the injury pattern, there was some increase in potentials followed by a gradual fall. At 60 minutes, after ligation of the epicardial potentials coronary arteries, were less than the control values in 3 few animals (Table II). Jlaxwell, Kennamer, and Prinzmetal’ also reported abnormally “large ‘R’ waves occurring over the noncontractile muscle during the stage of acute injury” after the ligation of the coronary artery. On the other hand, some reduction in voltage of epicardial QRS complex over injured or infarcted myocardium has also been reported by other workers.Y-10 Although in the present study there was usually a slight initial increase in epicardia1 potential with concomitant fall in endocardial potential after ligation of the coronary arteries, there was later no such consistent reciprocal relationship between simultaneously recorded epicardial and endocardial potentials, from either anterior or inferior walls of the left ventricle. For example, in Dog 8 (Table I I), there was concomitant fall in both epi- and endocardial potentials recorded from inferior surfaces of the left ventricle (Fig. 1). Thus, persistently low ECP following coronary artery occlusion is unlikely to be due only to cancellation of the potentials at different sites of the ventricle. Falls of LV dp/dt and aortic pressures following experimental myocardial ischemia or infarction, as observed in this study, have been reported by other workersIn-r3 but the relation between postocclusion changes in LV dp/dt and ECP following coronary artery occlusion has not been previously studied. In general, a fall in LV or RVECP occurred with marked fall in LV dp/dt and there was a moderate correlation between percentage changes in ECP and changes in LV dp/dt. Pruett and Wood+ showed significant positive correlation between the amplitude and rate of depolarization of intracellular action potential and myocardial contractile force. In the present study, as preload and afterload were not
l’olumc Number
82 3
Ventricular
120-
endocardiul
potentials
3.59
120.
n I
loo-
8
loo-
* .
e
80. n
..
80-
m
8\
.
..
.
pa
.
. .
.
360-
zi
. . .
.
.
i .
nm
5 60-
. .
8
. .
.
. mm
8
8.
.I
n
m
.
m=
40-
40-
m
.
.
r = 0.568
r = 0.548
a 20-l
A
20
40
mm
60
LVECP
.
n
n 8
n . .
.
.
. ..
.
3 \
n8
80
201
100
(Ant)
Fig. 5. Relations between percentage changes and endocardial potential from left ventricular inferior wall (right, r = 0.548, P < 0.001).
1
20
I
40
I
60
B
RVEC
I 100
80
P
in the rate of rise of left ventricular pressure pulse anterior wall (left, r = 0.568, P < 0.001) and right
controlled, observed changes in LV dp/dt cannot be regarded as being representative of true changes in myocardial contractility. I5 Hence, although a moderate correlation was found between changes in LV dp/dt and ECP, the relationship between myocardial contractility and ECP remain uncertain and further study will be needed for its elucidation. In conclusion, it can be said that the present study has demonstrated that falls in ventricular endocardial potentials may occur following acute coronary artery OCelusion, but the precise mechanism remains obscure. It would seem that localized ischemia or infarction of the myocardium may not be directly responsible for the low ECP. Neither does the phenomenon of cancellation of electrical forces at different parts of the ventricles appear to be the cause of persistently low ECP following acute coronary artery occlusion. The practical importance of the fall in ECP after infarction lies in the use of demand (ventricular inhibited) pacing when needed. In demand pacing, the signal used to inhibit the pacemaker is the QRS potential. When this potential falls below the sensitivity of the pacemaker, the unit behaves as a fixed-rate apparatus, allowing competition to occur between the pa-
I 120 (LV dp/dt) ventricular
110 100
m m
1
i’
go-
3 80n
5 702 6050- : m 403OL
40
50 60 70 80 90 100 LVECP (Ant)
Fig. 6. Relation between endocardial potentials recorded simultaneously from the anterior and inferior walls of the left ventricle following coronary artery occlusion. There was no correlation between LVECP Ant. and LVECP Inf. (r = 0.128, P > 0.10).
tient’s own rhythm and the artificial stimulus of the pacemaker. Thus inappropriate ventricular stimulation may occur, increasing the risk of ventricular fibrillation.lJ6
.,lr,t. ilrurt J. Sc~tcwI)cr, 1971
Fig. 7. Two left ventricular endocardial electrodes in a heart examined by injection of dye. Both electrodes were moved at the time of photographs. One electrode was in a nonischemic (dark) area, indicated by the larger arrow, and the other in ischemic areas, indicated by the smaller arrow. Potentials recorded simultaneously from both sites fe!l following ligation of the left circumflex artery.
Summary
The behavior of right and left ventricular endocardial potentials (ECP) was studied in open-chest anesthetized dogs, both before and after ligation of the coronary artery. Endocardial potentials were recorded from the anterior and inferior walls of the left ventricle (LVECP Ant., LVECP Inf.) and from the inferior wall of the right ventricle (RVECP). Direct epicardial potentials from the anterior and inferior surfaces of the left ventricle, along with ECG Lead II, were also recorded. LV dp/dt and aortic pressure were monitored simultaneously. Following ligation of the coronary arteries, LVECP Ant. fell in all animals, and LVECP Inf. and RVECP in most, and remained lower than the control values throughout the periods of observation. Fall in ECP occurred whether the endocardial electrodes were in contact with ischemic or nonischemic endocardium. No relationship was found between the postocclusion changes in simultaneously recorded epi- and endocardial potentials whether from the anterior or inferior surface of the left ventricle. Neither was any correlation between the changes in endocardial potentials recorded from anterior and inferior surfaces of the left ventricle or between LVECP and RVECP. These find-
ings suggest that the fall in ECP which occurs following acute coronary artery occlusion is unlikely to be due to the phenomenon of cancellation between electrical forces generated at different parts of the ventricle. Neither localized ischemia nor infarction of the myocardium seems directly responsible for the fall in ECP. The precise mechanism remains obscure. Fall in LV dp/dt and in aortic pressure occurred in most animals following ligation of coronary arteries and there was moderate correlation between postocclusion changes in LV dp/dt and changes in ECP. We are grateful to the Pharmaceuticals Division of I.C.I., Ltd., Macclesfield, Cheshire, England, for allowing us to perform this study in their laboratory. We are also grateful to Drs. G. A. H. Miller (Brompton Hospital, London), A. Leatham, A. H. M. Harris (St. George’s Hosoital. London), and D. Fitzgeraid (I.C.1, Ltd.), ‘and’ to Prof.’ A. M. Barrett (Leeds University) for their help and encouragement. We are also grateful to Mrs. Iris Long for her secretarial help. REFERENCES 1.
2.
Chatterjee, K., Sutton, R., and Davies, J. G.: Low intracardial potentials in mvocardial infarction as a cause of failure of inhibition of demand pacemakers, Lancet 1511, 1968. Chatterjee, K., Harris, A., Davies, G., and Leatham, A.: Fall of endocardial potentials following acute myocardial infarction, Lancet 1:1308, 1970.
Volume 82 Number 3
3. Parker, B., Furman, S., and Escher, D. J. W.: Input signals to pacemakers in a hospital environment, Ann. N. Y. Acad. Sci. 167:823,1969. 4. Levine, D. H., Hellems, H. K., Dexter, L., and Tucker, S. A.: Studies in intracardiac electrocardiography in man. II. The potential variations in the right ventricle, AMER. HEART J. 37 ~64, 1949. 5. Hellerstein, H. J., and Katz, L. N.: The electrical effects of injury at various myocardial locations, AMER. HEART J. 36:184, 1948. 6. Chatterjee, K., Sutton, G. C., and Miller, G. A. H.: Right ventricular endocardial potentials in acute massive pulmonary embolism, Br. Heart J. (In press.) 7. Maxwell, M., Kennamer, R., and Prinzmetal, M.: Studies on the mechanism of ventricular activity. The mural type coronary QS wave, Amer. J. Med. 17:614, 1954. 8. Kaiser; G. A., Waldo, A. L., Harris, P. D., Bowman. F. 0.. Hoffman. B. F.. and Malam. J. R.: New method to delineate myocardial damage at surgery, Circulation 39 (Suppl. 1):83, 1969. 9. Durrer, D., Van Lier, A. A. W., and Buller, J.: Epicardial and intramural excitation in chronic myocardial infarction, AMER. HEART J. 68:765, 1969. 10. Prinzmetal, M., Shaw, C. M., Maxwell, M. H., Flamm, E. J., Goldman, A., Kimura, N., Rakita, L., Bordnas, J., Rothman, S., and
Ventricular
11.
12.
13.
14.
15.
16.
endocardial
potentials
361
Kennamer, R.: Studies on the mechanism of ventricular activation. VI. The depolarization complex in pure subendocardial infarction. Role of the subendocardial region in the normal electrocardiogram. Amer. I. Med. 16:469. 1959. Hood, WY B. J., Covelli, V. H., and’ Norman, J. C.: Acute coronary occlusion in pigs: Effects of acetyl strophanthidin, Cardiovasc. Res. 3:441, 1969. Hood, W. B., Kumar, R., Katayama, I., Neiman, R. S., and Norman, J. C.: Experimental myocardial infarction. 1. Production of left ventricular failure by gradual coronary occlusion in intact conscious dogs, - Cardiovasc. Res. 4:73, 1970. Regan, T. J., Markov, A., Oldewurfel, H. A., and Burke. W. M.: Mvocardial metabolism and function d’uring ischaemia; response to l-noradrenaline, Cardiovasc. Res. 4:334, 1970. Pruett, J. K., and Woods, E. F.: The relationships of intracellular depolarization rates and contractility in the dog ventricle in situ; effects of positive and negative ionotrophic agents, J. Pharmacol. Exp. Ther. 157:1, 1967. Mason, D. T. : Usefulness and limitations of the rate of rise of intraventricular pressure (DP/Dt) in the evaluation of myocardial contractility in man, Amer. J. Cardiol. 23:516, 1969. Chatteriee. K.. Harris. A.. and Leatham. A.: The risk of pacing after infarction and current recommendations, Lancet 2:1061, 1969.
L
ow right ventricular endocardial potentials (RVECP) in patients with acute myocardial infarction have been previously reported, 1-3 but the mechanisms remain unexplained. It is not known, for example, whether the low ECP is due to the electrode being in contact with ischemic endocardium or not. Furthermore, the behavior of left ventricular endocardial potential (LVECP) and its relation to RVECP, following coronary artery occlusion, are also not known. In the clinical study, an apparent relationship was noted between the degree of fall of RVECP and the severity of clinical heart failure, but no hemodynamic measurements were performed to verify this clinical impression. The present study was designed to investigate, in dogs, the behavior of both right and left ventricular endocardial potentials and their relation to hemodynamic alterations following experimental complete coronary artery occlusion.
Methods Nine beagle dogs, 9.5 to 13.2 kilograms in body weight, were anesthetized with intravenous pentobarbitone (30 mg. per kilo-
after
experimental
M.R.C.P.(Edin.)*
gram) and their respiration was maintained mechanically by a positive pressure respirator (Palmer Starling Respirator). The chest was opened by midsternotomy in one dog and by left thoracotomy through the fifth intercostal space in eight dogs. The heart was exposed by excising the pericardium. For recording endo- and epicardial potentials, “hook” electrodes made of Nichrome wires (8/1,000 inch diameter) were used. The whole length of the electrodes, except at the tip in the case of endocardial, and at the “angle of the hook” in the case of epicardial electrodes, were insulated with Diamel varnish. The epicardial electrodes were attached to the superficial layers of the epicardium directly. The endocardial electrodes were introduced into the ventricular cavity through a No. 1 hypodermic needle and then gently withdrawn until the electrograms recorded showed characteristic ventricular intracavitary configuration with ST elevation contact pattern.4 In all experiments, unipolar potentials were recorded and, in two experiments, in addition, bipolar potentials were also recorded simultaneously from the same sites. The approximate distance between
From
the Cardiac Department. Brompton Hospital. London. S.W.3, and the Pharmaceutical Macckslield, Cheshire, England. Received for publication Nov. 18. 1970. Reprint requests to: Dr. Kanu Chatterjee, Department of Cardiology, CedarsSinai Medical calif. 90054. *Present address: Dept. of Cardiology. Cedars-Sinai Medical Center, Los Angeles, Calif.
352
American
Heart
Journal
September, 1971
Division.
Center.
I.C.I.
Los
Ltd.,
Angeles.
Vol. 82, No. 3, pp. 352-361
Volrrme 82
Number
Ventricular
3
the bipolar leads was l/l,OOOth inch. Needle electrodes were used for recording standard Lead II electrocardiograms (ECG). RVECPs were recorded from the inferior wall, near the apex. LVECPs were recorded from two sites: (1) the anterior wall in the left anterior descending artery territory (LVECP Ant.), and (2) the inferior wall in the left circumflex artery territory (LVECP Inf.). Left ventricular epicardial potentials (LVEPP) were recorded from the anterior surface in the anterior descending artery territory (LVEPP Ant.) and from the inferior surface in the left circumflex territory (LVEPP Inf.). No right ventricular epicardial potentials (RVEPP) were recorded. A cathetertipped micromanometer” was introduced into the cavity of the left ventricle through its apex and the first derivative of left ventricular pressure pulse (LV dp/dt) was determined by electronic differentiation. Aortic pressure was measured by left carotid artery cannulation. All parameters were recorded simultaneously on an eightchannel tape recorder (Precision Instruments) and permanent records were subsequently obtained on an eight-channel paper recorder (Minograph 81). The coronary artery to be ligated was first dissected and isolated near its origin and a cotton thread was placed loosely around it. After a control period of observation for 30 minutes, the artery was ligated and observations were continued for at least 60 minutes. At the end of the experiments, the animals were killed and the hearts were dissected to verify the positions of the endo- and epicardial electrodes. To delineate the ischemic areas, 15 to 20 C.C. of Coomassie Blue dye were injected at the root of the aorta in six dogs. After the animals had been killed and the hearts had been dissected, well-perfused areas were bright blue and the clearly unperfused areas remained gray. Thus the ischemic (nondyed) and the nonischemic (dyed) areas could be identified on both the epicardial and endocardial surfaces of the ventricles. Histological examinations were not performed. The calibration voltage for the measure*S. E. Laboratories,
Ltd.,
London,
Ew&nd.
endocardial
potentials
353
ment of the potentials was chosen according to the amplitude of the potential. The potential was defined as the total deflection of the QRS (without the ST) and the measurement taken was the average of ten complexes (ventricular premature beats were excluded), The control measurements of the potentials, LV dp/dt, and mean aortic pressure (PAO) at 30 minutes before the ligation of the coronary arteries were regarded as 100 per cent and the changes at subsequent observations, both immediately before (0 minute) and after ligation (t 10, 20, 30, 40, 50, and 60 minutes), were expressed as the percentage of the control values. Results In six of the nine dogs the left circumflex artery (LCA) was ligated; in two dogs the left main coronary artery (LMCA) was ligated: in one dog the left anterior descending (LAD) artery was ligated. In eight dogs the postocclusion changes were recorded at ten-minute intervals up to 60 minutes; in one animal ventricular fibrillation occurred 15 minutes after ligation of the LMCA, and in this dog the postocclusion changes were recorded only at ten minutes. A typical example of changes in LVECP and LVEPP following occlusion of a coronary artery is shown in Fig. 1. The percentage changes in the mean values of the potentials, LV dp/dt, and aortic pressures, both before and after ligation of the coronary arteries, are shown in Table I and Fig. 2. Postocclusion changes in individual experiments are shown in Fig. 3. The pre- and postocclusion potentials (in millivolts) are summarized in Table II. Endocardial potentials. LVECP Ant. fell in all nine dogs following coronary artery occlusion (Fig. 3, a). LVECP Inf., recorded in six dogs, fell in four and remained unchanged in two (Fig. 3, c). RVECP, recorded in seven dogs, fell significantly in four and remained unchanged in three (Fig. 3, e). The mean postocclusion ECP remained lower than the control values throughout the period of observation (Table I). The fall in ECP, when it occurred, was not related to the coronary artery ligated (Table II).
354
Chatterjee and Rouse
Fig. 1. Simultaneously recorded endo- and epicardial potentials from the anterior and inferior walls of the left ventricle, both before and after circumflex artery occlusion. Both LVECP Ant. and LVECP Inf. fell following occlusion. Transient rise in epicardial potentials with appearance of the injury pattern followed by gradual fall is also shown.
LVECP Ant. was recorded in all six hearts that were examined by injection of dye to delineate ischemic areas. LVECP Inf. and RVECP were recorded only in five such hearts. Fall in LVECP Ant. was observed whether the electrodes were in ischemic (three hearts) or in nonischemic areas (three hearts). The endocardial electrodes for LVECP Inf. were in ischemic areas in four (in three a fall in LVECP Inf. occurred and in one no change was observed) and in nonischemic areas in one heart (no change in LVECP Inf. occurred). The electrodes for RVECP were in ischemic areas in two hearts, but only in one of these did a fall in RVECP occur. In the remaining three hearts the electrodes
were in nonischemic areas and in two of these RVECP fell. Bipolar potentials. Bipolar and unipolar potentials were recorded simultaneously in two dogs from the same sites. Although the bipolar potentials were smaller in amplitude than unipolar potentials, the postocclusion changes were similar (Fig. 4). Epicardial potentials. LVEPP Ant. were recorded in nine dogs and LVEPP Inf. in six. After ligation of the coronary artery the changes in epicardial potentials were variable. In most dogs there was an initial increase in epicardial potentials with the appearance of the injury pattern (monophasic potential and marked ST elevation), followed by a gradual fall (Figs. 1 and 2). At
123 * 66.0 0.20 < P < 0.25
105 k 42.0 0.40 < P < 0.50
644.0 zk 14.8 P < 0.001
61.6 + 14.0 P < 0.001
61.6 Ik 14.5 P < 0.001
+40
-i-50
+60
*Values at 30 minutes before are also shown, along with
122 rt 76.0 0.25 < P < 0.30
63.1 + 19.3 P < 0.001
-l-30
coronary standard
(
artery occlusion deviation.
99.7 f 26.6 0.80 < P < 0.90
123 + 29.0 0.01 < P < 0.02
110 + 29.0 0.10 < P < 0.20
100 94.0 * 14.0
65.8 + 16.0 P < 0.001
100 + 3.7
4-20
101
LVEPP
72.6 + 13.3 P < 0.001
0
j
+10
-30
(Ant.)
(I?$)
100 99.5 f 4.6
LVECP
and PA0
were
regarded
1
(I$.)
cent
and
( 100 t 5.8
78.1 + 22.5 P = 0.02
101
RVECP
arteries*
changes
, 100 93 + 9.0
LeadII
as percentage
105 + 29.9 0.30 < P < 0.40
134 + 36 0.005 < P < 0.01
120 k 24 0.01 < P < 0.02
119 + 34 0.05 < P < 0.10
114 + 58 0.30 < P < 0.90
134 f 64 0.10 < P < 0.20
are expressed
82.5 f 29.9 0.05 < P < 0.10
72.6 + 30.2 0.025 < P < 0.05
78.8 + 21.1 0.01 < P < 0.02
82.6 + 29.1 0.05 < P < 0.10
85.6 + 24.4 0.10 < P < 0.20
the subsequent
86 + 30 0.20 < P < 0.25
92 + 40 0.50 < P < 0.60
107 f 36 0.70 < P < 0.80
111 Ik 35 0.50 < P < 0.60
111 zk 34 0.50 < P < 0.60
125 + 39.0 0.05 < P < 0.10
100 102 * 7.4
LVEPP
after ligation of coronary
as 100 per
64.3 rt 26.5 0.005 < P < 0.01
64.8 J- 25.9 0.005 < P < 0.01
69.6 f 28.6 0.025 < P < 0.05
71 f 18.7 0.001 < P < 0.005
78.5 It 18.0 0.005 < P < 0.01
87.8 + 14.1 0.05 < P < 0.10
(Ant.)
LVECP
off,
(
LV dp/dt,
Table I. Changes in potentials,
100 102.8 + 11.2
LV dp/&
values.
Statistical
66.6 rt 25.3 0.005 < P < 0.01
56 + 24.8 P < 0.001
69.5 + 21.3 0.001 < P < 0.005
68.3 + 21.7 0.001 < P < 0.005
62 i- 11.5 P < 0.001
66.5 rk 25.0 0.001 < P < 0.005
of these
/
/
100 + 10.5
significance
(P values)
86 zb 25.7 0.05 < P < 0.10 88.6 * 31.4
82.0 5 26.0 0.025 < P < 0.05
88.3 i 31.3 0.10 < P < 0.20
99 * 8.8 0.10 < P < 0.20
108
PA0 (mean)
356
-50 ’ I 0
Am Heart I. .Sc/hwber, 1971
Chutterjce und Roux
I 10
Fig. 2. Percentage tials, LV dp/dt, coronary arteries.
I I I 20 30 40 Time (minutes) changes and PA0
in mean following
I 50
I 60
values of potenligation of the
60 minutes, LVEPP Ant. was slightly increased in four dogs, slightly reduced in three, and unchanged in two dogs, as compared with control values (Table II, Fig. 3, c). Similarly, LVEPP Inf. at 60 minutes was reduced in four dogs and increased in two, as compared with control values (Table II and Fig. 3, d). The changes in epicardial potentials were not related to the coronary artery ligated. No correlation was present between postocclusion percentage change of LVEPP Ant. and LVEPP Inf. ; neither was there any correlation between changes in LVECP Ant. and LVEPP Ant. or LVECP Inf. and LVEPP Inf. In six hearts that were examined by injection of dye, the epicardial electrodes, on both the anterior and inferior walls of the left ventricle, were in mottled areas; whether the electrodes were in ischemic or nonischemic areas could not be precisely determined. Potentials in Lead II. Lead II ECG’s recorded in seven of the nine dogs showed variable changes following ligation of the coronary arteries. QRS potentials increased initially in most dogs, with the
appearance of the injury pattern (ST elevation) followed by a gradual fall of QRS potential (Fig. 2). At 60 minutes it was slightly increased in four dogs, slightly reduced in two, and unchanged in one (Table II). The changes in potentials were not related to the coronary artery ligated (Fig. 3, f). Rate of rise of LV dp/dt. The changes in LV dp/dt were recorded in seven of the nine dogs. After ligation of the coronary arteries, reduction occurred in all but one dog (Fig. 2, g). The mean postocclusion reduction was significant at all periods of observation (Table I). The correlation between postocclusion changes in LV dp/dt and in LVECP and between LV dp/dt and RVECP are shown in Fig. 5. Moderate but significant correlation was found between changes in LV dp/dt and LVECP (r = 0.568, P < 0.001) and between LV dp/dt and RVECP (r = 0.548, P < 0.001). Changes in PA0 were recorded in seven of the nine dogs; there was an initial fall in five dogs and no significant change in two following ligation of the coronary arteries (Fig. 3, h). In general the fall in PA0 was not marked and in most dogs PA0 returned almost to control level at 60 minutes after ligation of the coronary arteries. No correlation was found between the changes in PA0 and changes in LVECP or RVECP. Discussion The clinical observation that a fall in ventricular endocardial potentials may occur following acute coronary artery occlusion was confirmed in this study. In all animals, during the control period of observation, there was no change either in left or right ventricular endocardial potentials. Following ligation of the coronary arteries, LVECP Ant. fell in all animals and LVECP Inf. and RVECP in most. The fall in endocardial potential occurred soon after ligation and the values remained lower than the control values throughout the periods of observation. The present study also demonstrated that postocclusion changes in endocardial potentials recorded simultaneously from the two ventricles or from the different sites of the same ventricles may vary. In Dogs 4 (LC ligated) and 5 (LMC ligated), LVECP Ant. fell but no changes were observed in LVECP Inf. or in RVECP
Vcnlridar
Time
of occlusion
o
oOcclusion
of L. M. C. A.
*Occlusion mOcclusion
of L.C. A. of L. A. D.A.
Time
endocardial
of
OccluSiOn
potentials
3.57
Of
loo2iz u *
20
0
LVECP (Ant) 0’
LVEPP (Ant)
LVECP 04
+60 O+60 0+do Time (Minutes) (4
04
LVEPP w o-
(4
Fig. 3. Changes in individual exoeriments Lv dp/dt (gj, and mean PA0 (h).
8060.
20
0
+60
RVECP 0+iOb (4
(4 at 60 minutes
(Table II). The explanation for this difference remains obscure but it is unlikely to be due to the cancellation of the potentials at the two surfaces of the ventricle as no reciprocal relation was found between LVECP Ant. and LVECP Inf. (Fig. 6). The changes in ECP in this study could not be attributed to electrode position in relationship to ischemic or nonischemic endocardium (Fig. 7). In six hearts examined with injection of dye to delineate ischemic and nonischemic endocardium, the endocardial electrodes at the anterior wall of LV were in ischemic areas in three and in nonischemic areas in the other three, but LVECP Ant. fell in all. In two of the same six hearts, however, where LVECP Inf. and RVECP were also recorded simultaneously with LVECP Ant., no fall occurred in LVECP Inf. in one and in RVECP in the other, although the endocardial electrodes were in contact with ischemic endocardium. The explanation of this lack of change in ECP recorded from the ischemic area remains obscure. Hellerstein and Katq6 while investigating LLelectrical effects” of experimental myocardial injury in dogs, also reported in some animals no alteration in “QS complexes recorded from a subjacent electrode within the right ventricular cavity after local coagulation of a large area of the anterior
ECG Lead 2 LV dp/dt +60 0+dO Time (Minutes)
after
ligation
(f)
of the coronary
Time
Ff? 40.
. -30
. -20
Fig. 4. Changes in (open circles) and from the anterior and after ligation
PAo(mean) Ot60 (h)
cd arteries,
of occlusion of L.C.& . . . . -10 0 +lO +20 Time (minutes)
potentials
(a to!),
. . . . +30 +40 +50 +60
simultaneously recorded unipolar bipolar (closed circles) potentials wall of the left ventricle before of the left circumflex artery.
wall of the right ventricle.” Hence, although the relationship between localized myocardial ischemia or infarction and fall of ECP remains uncertain, these findings suggest that it is not due to the electrode being in contact with ischemia or infarcted endocardium or only due to loss of local potentials. It also appears that myocardial infarction, per se, may not be directly responsible for the fall in ECP. This is also supported by the clinical observation that transient fall in RVECP may occur in patients undergoing open-heart surgery under deep hypothermia2 and in some patients with acute massive pulmonary em-
IJisni 11itlrout pre\.ious c.artliorcsl~ir;ltur) disease.” The poslocclusion changes in direct epicardial potential and in potential recorded in Lead II were variable. In most experiments, immediately after coronary artery ligation and concurrent with the appearance of the injury pattern, there was some increase in potentials followed by a gradual fall. At 60 minutes, after ligation of the epicardial potentials coronary arteries, were less than the control values in 3 few animals (Table II). Jlaxwell, Kennamer, and Prinzmetal’ also reported abnormally “large ‘R’ waves occurring over the noncontractile muscle during the stage of acute injury” after the ligation of the coronary artery. On the other hand, some reduction in voltage of epicardial QRS complex over injured or infarcted myocardium has also been reported by other workers.Y-10 Although in the present study there was usually a slight initial increase in epicardia1 potential with concomitant fall in endocardial potential after ligation of the coronary arteries, there was later no such consistent reciprocal relationship between simultaneously recorded epicardial and endocardial potentials, from either anterior or inferior walls of the left ventricle. For example, in Dog 8 (Table I I), there was concomitant fall in both epi- and endocardial potentials recorded from inferior surfaces of the left ventricle (Fig. 1). Thus, persistently low ECP following coronary artery occlusion is unlikely to be due only to cancellation of the potentials at different sites of the ventricle. Falls of LV dp/dt and aortic pressures following experimental myocardial ischemia or infarction, as observed in this study, have been reported by other workersIn-r3 but the relation between postocclusion changes in LV dp/dt and ECP following coronary artery occlusion has not been previously studied. In general, a fall in LV or RVECP occurred with marked fall in LV dp/dt and there was a moderate correlation between percentage changes in ECP and changes in LV dp/dt. Pruett and Wood+ showed significant positive correlation between the amplitude and rate of depolarization of intracellular action potential and myocardial contractile force. In the present study, as preload and afterload were not
l’olumc Number
82 3
Ventricular
120-
endocardiul
potentials
3.59
120.
n I
loo-
8
loo-
* .
e
80. n
..
80-
m
8\
.
..
.
pa
.
. .
.
360-
zi
. . .
.
.
i .
nm
5 60-
. .
8
. .
.
. mm
8
8.
.I
n
m
.
m=
40-
40-
m
.
.
r = 0.568
r = 0.548
a 20-l
A
20
40
mm
60
LVECP
.
n
n 8
n . .
.
.
. ..
.
3 \
n8
80
201
100
(Ant)
Fig. 5. Relations between percentage changes and endocardial potential from left ventricular inferior wall (right, r = 0.548, P < 0.001).
1
20
I
40
I
60
B
RVEC
I 100
80
P
in the rate of rise of left ventricular pressure pulse anterior wall (left, r = 0.568, P < 0.001) and right
controlled, observed changes in LV dp/dt cannot be regarded as being representative of true changes in myocardial contractility. I5 Hence, although a moderate correlation was found between changes in LV dp/dt and ECP, the relationship between myocardial contractility and ECP remain uncertain and further study will be needed for its elucidation. In conclusion, it can be said that the present study has demonstrated that falls in ventricular endocardial potentials may occur following acute coronary artery OCelusion, but the precise mechanism remains obscure. It would seem that localized ischemia or infarction of the myocardium may not be directly responsible for the low ECP. Neither does the phenomenon of cancellation of electrical forces at different parts of the ventricles appear to be the cause of persistently low ECP following acute coronary artery occlusion. The practical importance of the fall in ECP after infarction lies in the use of demand (ventricular inhibited) pacing when needed. In demand pacing, the signal used to inhibit the pacemaker is the QRS potential. When this potential falls below the sensitivity of the pacemaker, the unit behaves as a fixed-rate apparatus, allowing competition to occur between the pa-
I 120 (LV dp/dt) ventricular
110 100
m m
1
i’
go-
3 80n
5 702 6050- : m 403OL
40
50 60 70 80 90 100 LVECP (Ant)
Fig. 6. Relation between endocardial potentials recorded simultaneously from the anterior and inferior walls of the left ventricle following coronary artery occlusion. There was no correlation between LVECP Ant. and LVECP Inf. (r = 0.128, P > 0.10).
tient’s own rhythm and the artificial stimulus of the pacemaker. Thus inappropriate ventricular stimulation may occur, increasing the risk of ventricular fibrillation.lJ6
.,lr,t. ilrurt J. Sc~tcwI)cr, 1971
Fig. 7. Two left ventricular endocardial electrodes in a heart examined by injection of dye. Both electrodes were moved at the time of photographs. One electrode was in a nonischemic (dark) area, indicated by the larger arrow, and the other in ischemic areas, indicated by the smaller arrow. Potentials recorded simultaneously from both sites fe!l following ligation of the left circumflex artery.
Summary
The behavior of right and left ventricular endocardial potentials (ECP) was studied in open-chest anesthetized dogs, both before and after ligation of the coronary artery. Endocardial potentials were recorded from the anterior and inferior walls of the left ventricle (LVECP Ant., LVECP Inf.) and from the inferior wall of the right ventricle (RVECP). Direct epicardial potentials from the anterior and inferior surfaces of the left ventricle, along with ECG Lead II, were also recorded. LV dp/dt and aortic pressure were monitored simultaneously. Following ligation of the coronary arteries, LVECP Ant. fell in all animals, and LVECP Inf. and RVECP in most, and remained lower than the control values throughout the periods of observation. Fall in ECP occurred whether the endocardial electrodes were in contact with ischemic or nonischemic endocardium. No relationship was found between the postocclusion changes in simultaneously recorded epi- and endocardial potentials whether from the anterior or inferior surface of the left ventricle. Neither was any correlation between the changes in endocardial potentials recorded from anterior and inferior surfaces of the left ventricle or between LVECP and RVECP. These find-
ings suggest that the fall in ECP which occurs following acute coronary artery occlusion is unlikely to be due to the phenomenon of cancellation between electrical forces generated at different parts of the ventricle. Neither localized ischemia nor infarction of the myocardium seems directly responsible for the fall in ECP. The precise mechanism remains obscure. Fall in LV dp/dt and in aortic pressure occurred in most animals following ligation of coronary arteries and there was moderate correlation between postocclusion changes in LV dp/dt and changes in ECP. We are grateful to the Pharmaceuticals Division of I.C.I., Ltd., Macclesfield, Cheshire, England, for allowing us to perform this study in their laboratory. We are also grateful to Drs. G. A. H. Miller (Brompton Hospital, London), A. Leatham, A. H. M. Harris (St. George’s Hosoital. London), and D. Fitzgeraid (I.C.1, Ltd.), ‘and’ to Prof.’ A. M. Barrett (Leeds University) for their help and encouragement. We are also grateful to Mrs. Iris Long for her secretarial help. REFERENCES 1.
2.
Chatterjee, K., Sutton, R., and Davies, J. G.: Low intracardial potentials in mvocardial infarction as a cause of failure of inhibition of demand pacemakers, Lancet 1511, 1968. Chatterjee, K., Harris, A., Davies, G., and Leatham, A.: Fall of endocardial potentials following acute myocardial infarction, Lancet 1:1308, 1970.
Volume 82 Number 3
3. Parker, B., Furman, S., and Escher, D. J. W.: Input signals to pacemakers in a hospital environment, Ann. N. Y. Acad. Sci. 167:823,1969. 4. Levine, D. H., Hellems, H. K., Dexter, L., and Tucker, S. A.: Studies in intracardiac electrocardiography in man. II. The potential variations in the right ventricle, AMER. HEART J. 37 ~64, 1949. 5. Hellerstein, H. J., and Katz, L. N.: The electrical effects of injury at various myocardial locations, AMER. HEART J. 36:184, 1948. 6. Chatterjee, K., Sutton, G. C., and Miller, G. A. H.: Right ventricular endocardial potentials in acute massive pulmonary embolism, Br. Heart J. (In press.) 7. Maxwell, M., Kennamer, R., and Prinzmetal, M.: Studies on the mechanism of ventricular activity. The mural type coronary QS wave, Amer. J. Med. 17:614, 1954. 8. Kaiser; G. A., Waldo, A. L., Harris, P. D., Bowman. F. 0.. Hoffman. B. F.. and Malam. J. R.: New method to delineate myocardial damage at surgery, Circulation 39 (Suppl. 1):83, 1969. 9. Durrer, D., Van Lier, A. A. W., and Buller, J.: Epicardial and intramural excitation in chronic myocardial infarction, AMER. HEART J. 68:765, 1969. 10. Prinzmetal, M., Shaw, C. M., Maxwell, M. H., Flamm, E. J., Goldman, A., Kimura, N., Rakita, L., Bordnas, J., Rothman, S., and
Ventricular
11.
12.
13.
14.
15.
16.
endocardial
potentials
361
Kennamer, R.: Studies on the mechanism of ventricular activation. VI. The depolarization complex in pure subendocardial infarction. Role of the subendocardial region in the normal electrocardiogram. Amer. I. Med. 16:469. 1959. Hood, WY B. J., Covelli, V. H., and’ Norman, J. C.: Acute coronary occlusion in pigs: Effects of acetyl strophanthidin, Cardiovasc. Res. 3:441, 1969. Hood, W. B., Kumar, R., Katayama, I., Neiman, R. S., and Norman, J. C.: Experimental myocardial infarction. 1. Production of left ventricular failure by gradual coronary occlusion in intact conscious dogs, - Cardiovasc. Res. 4:73, 1970. Regan, T. J., Markov, A., Oldewurfel, H. A., and Burke. W. M.: Mvocardial metabolism and function d’uring ischaemia; response to l-noradrenaline, Cardiovasc. Res. 4:334, 1970. Pruett, J. K., and Woods, E. F.: The relationships of intracellular depolarization rates and contractility in the dog ventricle in situ; effects of positive and negative ionotrophic agents, J. Pharmacol. Exp. Ther. 157:1, 1967. Mason, D. T. : Usefulness and limitations of the rate of rise of intraventricular pressure (DP/Dt) in the evaluation of myocardial contractility in man, Amer. J. Cardiol. 23:516, 1969. Chatteriee. K.. Harris. A.. and Leatham. A.: The risk of pacing after infarction and current recommendations, Lancet 2:1061, 1969.