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Slowing of the heart by paired pulse pacemaking
New Methods Slowing
of the Heart
by Paired
Pulse Pacemaking* WILLLW
hf.
CHARDACK,
M.D.,
ANDREW Buffalo,
I
A. New
RECENT years, increasing use has been made of electrical currents to control the rhythm of the heart. In addition to ventricular fibrillation, a number of disorders of rhythm can now be treated by countershock, and pacemaking by external or implanted devices has become routine therapy for complete atrioventricular block. A recent abstract by Lopez et al.’ indicated that the heart could also be electrically driven at rates lower than that of the sinus node. This was accomplished in dogs with 2 v. pulses of 150 to 250 msec. duration delivered through electrodes on the right ventricle. The same effect was obtained by using pairs of stimuli, of 3 msec. duration, with an interval of 150 to 250 msec. separating the pulses of each pair. The many potential applications, experimental as well as clinical? of an induced, controlled and maintained reduction of the heart rate prompted us to undertake experimentation along similar lines. The results of these studies form the basis for this report.
M.D. and DAVID C. DEAN,
M.D.
York
tain spontaneously occurring bigeminal arrhythmias, an instance of which is illustrated in Figure 1. A left or transverse thoracotomy was performed on 20 dogs under anesthesia with sodium pentobarbital, 30 mg. /kg. of body weight. Respirations were maintained by administering 100% oxygen through a cuffed endotracheal tube with a positive pressure demand valve (Pneophore-Mine Safety Appliance Company). The pericardium was opened. Stimulation was carried by wire electrodes, bipolar surface electrodes and intracardiac catheter electrodes. The electrocardiogram was recorded from conventional surface leads and directly from the auricles and ventricles. Left auricular, left ventricular, right ventricular and aortic arch pressures were recorded through polyethylene tubes (PE-200) connected to Sanborn transducers. Multiple runs (20 to 30) were made on each experimental preparation and the afore-mentioned data were inscribed in varying combinations on a Sanborn multichannel recorder. Additional parameters were studied in some experiments as described herein. Preliminary experiments were conducted on the first 2 dogs to gain familiarity with the technic. A line-powered Grass stimulator was used in these instances. It is well known that there are dangers of producing ventricular fibrillation when line-powered electrical instruments are used on direct myocardial electrodes. In this experimental application, this might lead to particularly confusing results since the safety of the method itself in regard to the provocation of ventricular fibrillation was under scrutiny. To exclude the possibility of ventricular fibrillation from minute circulating 60 cycle ground currents, a transistorized battery-driven, coupled pulse generatort (Fig. 2) was used for all subsequent experiments.
N
METHODS
GAGE,
AND MATERIALS
The method, at least in our hands and in its most consistently effective form, involves the introduction of a premature ventricular depolarization, If the latter occurs early enough in the cardiac cycle, no detectable contractile response is elicited by it. This electrical event is followed by a compensatory pause. If the first stimulus of the next pair is then fired before termination of this pause, the effective mechanical rate of the heart can be slowed to close to 50 per cent of the inherent rate or to any lesser degree. The pattern obtained by the paired stimuli resembles cer-
t Designed and manufactured Minneapolis, Minn.
by Medtronic,
Inc.,
* From the Departments of Surgery and Medicine, Veterans Administration Hospital, Buffalo, N. Y., and the State University of New York at Buffalo School of Medicine. This study was supported in part by a grant-in-aid from the Heart Association of Erie County, Inc., Buffalo, N. Y. 374
THE AMERICANJOURNAL OF CARDIOLOGY
Paired
375
Pulse Pacemaking
FIG. 1 (Experiment 20). A, left ventricular pressure (calibration: 25 mm. Hg per division). B, electrocardiogram. Spontaneous bigeminal arrhythmia observed in an anesthetized dog prior to any electrical stimulation. In cycles 2, 3 and 4 (from left to right), the extrasystole occurs relatively late (240 msec.) and produces a weak but significant extrasystole. In cycles 5, 6 and 7, the extraIn cardiac cycle 1, it occurs still systole occurs earlier, and the pressure event is barely detectable. In electrical slowing of the heart, the optimal earlier (170 msec.) and no pressure event is discernible. time relationship seen in cycle 1 is reproduced sequentially by paired electrical pulses separated by a critical fixed interval. With ventricular driving, the second stimulus of a pair must be administered near to or in the period of vulnerability; and for this reason, pacemaker stimuli were kept to near-threshold value (usually between 1 and 2 milliamperes).
Figure 3. The panel on the left shows a sinus rhythm with an interval of 400 msec. between cardiac cycles. The heart was then driven (middle panel) from a left ventricular electrode with paired stimuli at an interval of 590 msec. between pairs and an interval of 225 msec. between the pulses of each pair. The second depolarization occurs too late and is followed by a pressure event which, although feeble, must entail some expenditure of energy. On the panel to the right, the rate between pairs of stimuli is the same, but the interval between the pulses of each pair has been reduced to 190
RESULTS For brevity of presentation, the experiments performed have been summarized in Table I, and representative records have been selected to illustrate the most important aspects of this technic : (1) Ventricular Driving: This is illustrated in TABLE
Summary Experi“lent Dog No.
Sinus Rate
SlOWd Rate
Driving Site
146-167 167-187 134 108
86-115 115-120 96 86
LV LV LV LV
5 (396)
111-146
86-120
LV
6 (359) 7 (380)
166 167
120 111
LV LV
150-158 150 250 120
115-120 104-107 167 107
LV LV, RA LV
12 (417)
1.50
90
LA,
LV
t
13 (403)
130
88
RA,
LV
=
1 2 3 4
8 9 10 11
(384) (391) (392) (396)
(413) (408) (406) (414)
= = LA
107
LV
100 115 88
RA, LV, RA,
LV RA LV
18 (419) 19 (426) 20 (428)
177 162 150
109 79 100
RA, RV, LV,
RV LA RA
SEPTEMBER
Preliminary experiment Preliminary experiment Heart size recorded with induction coils VF following atropine & isoproterenol to increase sinus rate VF following z&opine & auricular loading with cold saline. Intramural P recorded Arch strain gauge on left ventricle Minor changes in mean flow in anterior descending coronary artery. See text Ascending aorta flow. See Figure 10 Atria1 tachycardia, electrically induced Spontaneous VT and spontaneous reversion to sinus tachycardia. See Figure 11 Coronary air embolization to produce acute left ventricular failure. Increase in LVP probably due to catheter artefact
VF following ligation nary artery
= = =
of anccrior
descmding
core-
Developed AF after atria1 driving Contmlled by ventricular driving. Also atria1 loading experiment. See Figure 6
zc
= =
= =
= left atrium; RV = right ventricle; fibrillation; AF = atria1 fibrillation;
1964
=
4 =
=
187
Comments
(LAD)
i
150 154 143
14,
Coronary Flow
4
14 (404)
VOLUME
LVP (Mean)
i
15 (427) 16 (405) 17 (434)
LV = left ventricle; LA pressure; VF = ventricular
I
of Experiments
RA
=
= =
Minor Minor
changes changes
in coronary in coronary
right atrium, AP = ascending aorta pressure; unchanged or insignificant changes; and LAD =
flow. flow.
See Figure
8
LVP = left ventricular left anterior descending.
Clllarclack.
376
INTERVAL
COUPLED-PULSE
-20
--
--
--.__L____
WIDTH
GENERATOR
Gage
and Ijean IIMC. No pressure rvcnt is then discernible following the second depolarization. (2) Myocmdial Confrac-tilif,:: Two of the experiments attempted to answer the following questions: (a) Does the second depolarization occur before the myocardium has recovered contractility, or (hj Is there, in fact, contraction of a significant number of fibers which escapes detection either because of asynchrony. or because of lack of sensitivity of the transducers in use? In the first of these experiments, ventricular contraction was recorded by an arch strain gauge sewed onto the surface of the left ventricle. Inspection of the strain gauge tracing fails to reveal any contractions that are not also seen on the left ventricular pressure record (Fig. 4). In a second set of experiments, intramyocardial pressure was recorded by connecting two polyethylene tuhes hy a 1 cm. long sleeve of collapsible, silicone rubber tubing. This segment was threaded into the depth of the left ventricular myocardium so that the stiffer polyethylene tubes were situated at both exits of the tunnel. The systrin was filled with saline and connected to the two ends of a transducer. The pressure in the tubes was adjusted to obtain pulsatile pressure recordings.
PRESSURE lEFT ATRIUM
200 PRESSURE AORTA
-
200 PCESSURI!
LEFT
VENTRICLE 0
ECG LEA0 2
ECG AURICULAR LEAD FIG. 3 (Experiment 15). Sinus rate (left) is 150 beats per minute; was slowed to 100 beats per minute by paired Compare optimal interval of 190 msec. (right) with less satisfactory timing (225 stimuli delivered to left ventrick. msec.) in the middle Fanel, followed by a slight but demonstrable second ventricular pressure event. No such event is discernible on the right panrl. THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Paired
Pulse Pacwnakin~
c.---I40 1, PRESSURE tEFT . VENTRICLE -----0
y------
140
PRESSURE AORTA
0 I’( , 3
STRAIN GAUGE
I
ECG
PAIRED STIMULI FIG. 4 (Experiment 6). Tracing obtained during slowing of the heart by paired stimuli delivered to the left ventricle. Two interspersed conducted beats (at A and B) have occurred before arrival of the first stimulus of a pair. As a consequence. the second depolarization of that pair is less premature than in the other cycles and leads to a discernible contraction. The latter is well defined as a separate contraction on the arch strain gauge trace. but it is also revealed on the left ventricular pressure trace by a slight change in contour.
It was thought that this technic might reveal asynchronous contractile events of some myocardial fibers in the vicinity of the compressible segment; however, inspection of the tracings fails to reveal any interruption of the smooth contour of the declining pressure during relaxation (Fig. 5). (3) Role of Left Ventricular Filling: Several experiments were designed to evaluate the role played by the degree and the rate of left ventricular filling. It was postulated that if a high rate of ventricular filling were made to prevail, the second depolarization might produce a separate discernible ventricular pressure event. The left atrium was cannulated with a large bore catheter (No. 30 French) connected to an elevated (50 cm.) reservoir of saline, and the flow of saline into the auricle was recorded with an electromagnetic flowmeter. In other runs, the ascending aorta was partially or completely occluded for a few beats. In several VOLUME
14,
SEPTEMBER
1964
runs (Fig. 6), both maneuvers were combined. The aorta was clamped and the reservoir opened. ,4lthough immediate filling and stretching of the ventricle must occur under these circumstances, the second stimulus of the pair was not followed by a separate contraction. (-I) Auricular Driving: Control of the heart rate could also be obtained by paired stimuli delivered to either auricle (Fig. 7). Adjustment of the rate and of the interval was more difficult with this modality. Placement of the electrodes on the auricle was critical because of the proximity of the phrenic nerve. If the latter is in the current field of the electrodes, synchronous contractions of the diaphragm are produced. (5) Coronary Blood Flow: In experiments on 3 animals, flow in the anterior descending coronary artery was recorded with an electromagnetic flowmeter (Fig. 7 and 8). Inspection of the record of pulsatile flow during sinus rhythm
378
PktSSURt ,NTRA-
JL,~%
: i ‘jim
MYOCARDIAL
.
.,
,
.~
I
VENTRICLE __--~~~
-O-
FIG. 5 (Experiment 5). Recording of intramyocardial pressure during slowing of the rate (cycles 1, 2 and 3, left to right) shows no evidence of myocardial contraction with the second depolarization.
FLOW
LEFT ATRIA1 CANNULA
PRESSURE AORTA
200 PRESSURE LEFT VENTRICLE
ECG
AND PAIRED STIMULI
FIG. 6 (Experiment 17). Slowing of the heart by paired pulses. At A, aorta was clamped. At B, saline Left ventricular pressure events continue at the rate of one conreservoir was emptied into atrium. traction for each two depolarizations. THE
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JOURNAL
OF CARDIOLOGY
Paired
Pulse
Pacemaking
PRESSURE AORTA
FIG. 7 (Experiment 7). The rate slowed to 111 beats per minute (left of vertical intercept) from 167 beats per minute by pairs of stimuli applied to auricle. Coronary flow (uppermost trace) continues throughout long diastole. Paper speed: 100 mm./sec.
shows the characteristic pattern of forward flow throughout the cardiac cycle but with a sharp reduction of the flow rate during systole. When the heart was slowed, coronary flow continued at high rates during the long diastole with only a slight decline during end-diastole, paralleling the fall in diastolic filling pressure. Forward flow during systole was more reduced during slowing, probably because of the greater forcefulness of the potentiated contraction. Peak flow rates were lower when the heart was slowed. Mean coronary flow most often remained unchanged when the heart was slowed (Fig. 7). In some runs it increased slightly, and in others a decrease was noted at the lower rate. These changes were small and mostly paralleled the slight changes and fluctuations of the blood pressure which occurred when the rate was artificially slowed or when it was permitted to return to sinus rhythm. (6) The Effect of Single Pulses: Numerous attempts to slow the heart electrically without producing two depolarizations for each contraction were unsuccessful. In a few experiments, using single pulses of 170 msec. duration, a slowing effect was seen in an occasional cardiac cycle, but it was not possible to obtain this effect In other runs, using pairs of stimconsistently. uli, the effect could be produced in every cycle, but slowing of only a minor degree (approximately 10%) could be obtained (Fig. 9). VOLUME
14,
SEPTEMBER
1964
(7) Hemodynamic Effectr of Slowing of Rate: Several experiments yielded information on the beneficial effects that can result from slowing of rates which were sufficiently rapid to induce adverse hemodynamic alterations in the animal. In 1 dog, atria1 tachycardia was produced by driving the atrium at 250 beats per minute from a separate pacemaker. The ventricular rate was then slowed to 160 by pairs of pulses delivered through a ventricular electrode; this resulted in significant improvement of the aortic pressure. In another animal, moderate tachycardia with pulsus alternans spontaneously developed, probably due to myocardial depression from barbiturate anesthesia. When the heart was slowed (Fig. 10) from 158 to 115 beats per minute, blood pressure and cardiac output rose although left ventricular pressure work fell significantly. In one animal (Fig. 11) ventricular tachycardia occurred spontaneously prior to any Elecattempts at electrical control of the rate. trical reduction of the rate by 36 per cent was beneficial in terms of an augmented blood presthe ventricular tachysure. Subsequently, cardia converted spontaneously into a sinus tachycardia, and blood pressure levels achieved during sinus tachycardia, although better than those seen with ventricular tachycardia, were still clearly inferior to those obtained with artificial slowing of the heart.
Chardack,
380 -_
Gag-e and Dean
__-_-200
PRESSURE LEFT VENTRICLE
PRESSURE A0 RTA
ECG
60 CORONARY FLOW y0 FIG. 8 (Experiment 19). Rate slowed to 100 beats per minute from 150 by paired stimuli applied to the right ventricle. Mean aortic pressure is little affected except for fluctuations at the time of the change in rates. Mean coronary flow (left anterior descending artery) is slightly higher at the faster rate. Note also the difference in instantaneous flow rates. Mean left ventricular pressure rises sharply at the higher rate. A, zero flow, by momentary occlusion of artery downstream to flow probe. DISCUSSION
Our experiments show that paired electrical stimuli, appropriately timed, can consistently slow the effective mechanical rate of the heart. The second stimulus of each pair elicits a ventricular depolarization very early in the cardiac cycle when excitability has returned but when recovery of contractility has as yet not occurred. This technic leads to an increase in the number of electrical events but to a decrease in the number of mechanical contractions. The increase in the number of electrical events above the control sinus rate is inversely proportionate to the degree of slowing. A detailed comparison of our results with those obtained by Lopez et al.’ cannot be made at this time since the account of their findings has as yet not appeared in print. A personal communication2 from the authors indicates that at least some of their experiments dealt with the same mechanism of two depolarizations pro-
duced
for each
attempts
mechanical
contraction.
Our
to obtain slowing of both the electrical
and the mechanical
rate were largely unsuccess-
ful, and when they were consistently successful, only minimal slowing could be obtained. It may well be that in this regard their experiments were more rewarding. In any event, the data so far obtained indicate that the rate of apparent ventricular contractions can be reduced to close to 50 per cent of the sinus rate. This can be accomplished with surface or endocardial electrodes from any of the four cavities. .4uricular driving was more difficult but has the obvious advantage of preserving normal atrioventricular synchronization and ventricular activation. Stimulation of the atrium should also be safer than ventricular driving since the stimulus, although premature, travels through the normal conduction system and is of physiologic amplitude. While this modality may THE
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JOURNAL
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CARDIOLOGY
Paired Pulse Pacemaking
FIG. 9. A. Experiment 5. Tracing shows that the second stimulus does not evoke a propagated response (cycles 1 through 4 from left). However, the rate is slowed to only 86 from the control sinus rate of 96 (cycles 5 through 9). Paper speed: 50 mm./sec. B, Experiment 2. Long pulses produce depolarizations at make and at break. In cycle 2, from left. the break fails to evoke a propagated response. The rate is 120. Control sinus rate was 187. Paper speed: 100 mm./sec.
lead to auricular fibrillation, on theoretic grounds, it should be less prone to provoke ventricular fibrillation. In practice, although a considerable number of experiments involved ventricular driving, ventricular fibrillation was observed in only a few instances and appeared to be related to the administration of drugs, interference with coronary circulation, and surgical manipulation of the heart. We gained the impression that ventricular driving with pulses of near-threshold amplitude appeared to be quite safe. This point is of crucial importance and requires further study and more specific documentation. Intracavitary and intramyocardial pressure recordings as well as arch strain gauge measurements indicate that either no contraction accompanies the second depolarization or that it is of insufficient amplitude to be detected by the measuring devices employed. These studies do not rule out completely the possibility that a significant number of fibers do contract but that their conVOLUME
14,
SEPTEMBER
1964
traction remains hidden because of asynchrony. Whether the second depolarization and the nonapparent mechanical contractionif it exists-entail a significant expenditure of energy also remains to be determined. The time relation between recovery of excitability and that of contractility is such that, in the dog, an interval of approximately 50 msec. is available for optimal placement of the second stimulus of the pair. The adjustment of the interval between pulses is critical and has been difficult to achieve on the basis of the electrocardiogram alone. A longer than optimal interval between pulses leads to extrasystolic pressure events which, since they are not accompanied by ejection, must of necessity reduce the efficiency of cardiac work. For these reasons, at least in our hands and at the present time, paired pulse pacemaking requires continuous monitoring of the pressure in one of the ventricles. Mean left ventricular pressure was consistently reduced during slowing in spite of an augmented
382
(ihardack,
Gage and 1l)ean
2500 MEAN
FLOW AORTA 0
PRESSURE AORTA
100 PRESSURE LEFT VENTRICLE 0
ECG
PAIRED STIMUll
FIG. 10 (Experiment 8). Tracings show effect of slowing of the heart on ascending aortic flow (cardiac output minus coronary flow) and on aortic pressure. Sinus rate of 158 beats per minute was slowed to 115 beats. Note The decrease in left ventricular diastolic pressure during slowing disappearance of pulsus alternans at slower rate. indicates enhanced contractility. Paper speed : 25 mm./sec. and 1 mm./sec. during recording of mean values.
systolic peak pressure. With increasing degrees of slowing, the decrease in the number of pressure events offsets and then outweighs the increase in the peak systolic pressure. Thus, the overall effect is a net reduction of the area under the left ventricular pressure curve per unit time. This area quantitatively describes the external pressure work, and the latter is one of the important determinants of coronary flow and oxygen consumption of the heart. Recor&ng$ uf mean coronary j?ow (in runs in which aortic pressure remained unchanged) did show a slight decrease at the slower rate (Fig. 8) but in many runs, there was no change in mean coronary flow except during the brief periods of adjustment which followed a change of rate. In some experiments, mean coronary flow was slightly higher at the slower rate. All in all, these changes in mean coronary flow were
surprisingly small in view of the very marked reduction observed in mean left ventricular pressure produced by slowing of the heart. Studies of tfle pulsatile coronary jowl during electrical slowing show the entire diastolic interval to be available for flow. It is possible that this long diastolic interval alters the regulatory mechanism of coronary flow, and this might explain the minor changes observed in mean coronary flow contrasting with the marked change in left ventricular pressure work. The observation that peak coronary flow rates were always lower, and in some instances markedly so, at the slower rate would support such an explanation. The mechanism of regulation of coronary flow is still a matter of debate, but there is increasing agreement that myocardial metabolic activity and oxygen consumption play an important part in it and that whenever energy THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Paired
Pulse
Pacemaking
PRESSURE AORTA
100
~
PRESSURE RIGHT VfNTRlCtE 0
ECG
FIG. 11 (Experiment 11). A, sinus rhythm at beginning of experiment (rate 120). B, spontaneous ventricular tachycardia prior to any electrical stimulation (rate 167). C, same as B, a few minutes later. Shows pulsus alternans (rate 158). D, improvement in pressure with slowing by paired pulse stimulation (rate 107). E, same as D, a few minutes later (rate 107). F, return to ventricular tachycardia on withdrawal of electrical stimuli (rate 134). G. spontaneous reversion. a few minutes later, to normal sinus rhythm (rate 134). Paper speed : 25 mm./sec. in panels A through D ; 10 mm./sec. in panels E, F and G.
expenditure outruns oxygen supply, intravascular resistance decreases and leads to an increase in coronary flow. The lower coronary flow rates observed when the heart was slowed would indicate a higher level of intravascular resistance and suggest that, although total coronary flow at the slower rate is not changed, the myocardium operates on a more favorable metabolic level. Because of the long diastolic interval at the artificially slowed rate, lesser flow rates This are required to yield a given mean flow. alteration in the diastolic time-flow relation may well be of significance when coronary flow rates are limited by the presence of obstructive coronary arterial disease. On the other hand, it is also possible that the second depolarization and the potentiation of the beats which occurs with electrical slowing entail significant energy expenditures and tend to raise coronary fiow requirements. These observations are fragmentary and based on relatively few experiThey require further substantiation ments. particularly in conjunction with determinations of oxygen consumption. Such studies are now in progress. Some degree of postextrasystolic potentiation was observed in all our experiments with paired VOLUME
14,
SEPTEMBER
1964
pulse pacemaking. It was manifest by an increase in peak systolic pressure and the greater forcefulness of the postextrasystolic contraction was also evidenced by a steeper rate of change of the ascending limb of the left ventricular pressure curve. A recent study by Siebens et a1.3 dealt in detail with this phenomenon, and some of their observations are relevant in this context. The greater the prematurity of the extrasystole, the weaker is the left ventricular pressure event produced by it. Also, the strength of a postextrasystolic contraction is always enhanced by comparison with preceding normal cardiac cycles, and this potentiation increases as a linear function of the prematurity of the extrasystole. In paired pulse stimulation, the prematurity of the extrasystole is such that the resultant contraction is either absent or cannot be measured, and since enhancement of the postcompensatory beat increases with extrasystolic prematurity, paired pulse stimulation entails maximal potentiation obtainable by prematurity. Siebens also showed that potentiation was affected by the interval elapsed between an a postextrasystolic-driven extrasystolic and beat and was maximal when the interval ap-
pwxinlated OIW and one-half’ cardiac c\~les. These observations arc pertinent to electrical slobving of the heart because the interval referred to corresponds to that between the second stimulus of a pair and the first of the following one. This suggests that maximal potential+ effects can be expected at the maximal rates of slowing obtainable with this technic, that is, at rates between SO and 60 per cent of the control sinus rate. Our clinical rxfwience with laired pulse ~nc-rmaking is limited, but the few observations made so far in the course of thoracotomy have established that the technic is applicable to the -4 discussion of its clinical uses human heart. is beyond the scope of this report except to suggest that cardiac catheterizations and postcardiotomy states come to mind readily as an area in which prudent evaluation of the technic could be initiated. This would entail only the leaving behind of a myocardial electrode wire and an intraventricular, small-diameter catheter, which subsequently can be withdrawn. Both technics have been used clinically and would permit slowing of the heart with constant monitoring of the right ventricular pres,4 controlled reduction of the heart rate sure. may be of value in postcardiotomy sinus tachycardias which cannot be adequately subdued by drugs. These are but a few clinical situations in which this technic might be explored and such studies are now in to advantage. progress.
depolarization occurs wit11 both stiiuuli of tlic pair, but no measurable contraction follows the second stimulus. Slowin,g of the heart by this technic leads to (a) a decrease in mean left \,entricular pressure? (b) a potentiation effect, and (c) higher cardiac output and blood pressure when used to correct tachycardias severe enough to produce adverse effects on these parameters. When the heart is slowed electrically, coronary flow continues throughout the long diastolic period. This technic has been used successfully in man in the course of thoracotomy. ADDENDUM Since submission of this manuscript, a personal communication from .J. F. Lopez indicates that a report on his studies entitled “Slowing the Heart Rate in Dogs by Artificial Electrical Pacing” is now in press in Circulation Research. Also, recent studies from our laboratory show that the sustained postextrasystolic potentiation produced by paired pulse stimuIation leads to a very significant increase in coronary tlow and oxygen consumption per beat. However, in regard to coronary flow and oxygen consumption per minute, this effect is offset in proportion to the reduction in rate. A detailed account of these studies is now in preparation. REFERENCES 1. I,DPEZ, J. F.,
A. and KATZ, L. N. Slowing of the heart rate by artificial electrical stimulation with pulses of long duration in the dog (Abstr.). EDELIST,
Circulation, 28: 759, 1963.
The rate of apparent ventricular contractions can be slowed by paired electrical stimuli separated by an interval of 150 to 250 msec. and applied to either ventricles or auricles. A
A. Personal communication. 3. SIEBENS, A. A.? HOFFMAN, B. F., CRANEFIELD, P. F. and McC. BROOKS, C. Regulation of contractile Am. J. force during ventricular arrhythmias.
2.
EDELIST,
Physiol., 197: 968, 1959.
TZIE AMERICAN JOURNAL OF CARDIOLOGY
of the Heart
by Paired
Pulse Pacemaking* WILLLW
hf.
CHARDACK,
M.D.,
ANDREW Buffalo,
I
A. New
RECENT years, increasing use has been made of electrical currents to control the rhythm of the heart. In addition to ventricular fibrillation, a number of disorders of rhythm can now be treated by countershock, and pacemaking by external or implanted devices has become routine therapy for complete atrioventricular block. A recent abstract by Lopez et al.’ indicated that the heart could also be electrically driven at rates lower than that of the sinus node. This was accomplished in dogs with 2 v. pulses of 150 to 250 msec. duration delivered through electrodes on the right ventricle. The same effect was obtained by using pairs of stimuli, of 3 msec. duration, with an interval of 150 to 250 msec. separating the pulses of each pair. The many potential applications, experimental as well as clinical? of an induced, controlled and maintained reduction of the heart rate prompted us to undertake experimentation along similar lines. The results of these studies form the basis for this report.
M.D. and DAVID C. DEAN,
M.D.
York
tain spontaneously occurring bigeminal arrhythmias, an instance of which is illustrated in Figure 1. A left or transverse thoracotomy was performed on 20 dogs under anesthesia with sodium pentobarbital, 30 mg. /kg. of body weight. Respirations were maintained by administering 100% oxygen through a cuffed endotracheal tube with a positive pressure demand valve (Pneophore-Mine Safety Appliance Company). The pericardium was opened. Stimulation was carried by wire electrodes, bipolar surface electrodes and intracardiac catheter electrodes. The electrocardiogram was recorded from conventional surface leads and directly from the auricles and ventricles. Left auricular, left ventricular, right ventricular and aortic arch pressures were recorded through polyethylene tubes (PE-200) connected to Sanborn transducers. Multiple runs (20 to 30) were made on each experimental preparation and the afore-mentioned data were inscribed in varying combinations on a Sanborn multichannel recorder. Additional parameters were studied in some experiments as described herein. Preliminary experiments were conducted on the first 2 dogs to gain familiarity with the technic. A line-powered Grass stimulator was used in these instances. It is well known that there are dangers of producing ventricular fibrillation when line-powered electrical instruments are used on direct myocardial electrodes. In this experimental application, this might lead to particularly confusing results since the safety of the method itself in regard to the provocation of ventricular fibrillation was under scrutiny. To exclude the possibility of ventricular fibrillation from minute circulating 60 cycle ground currents, a transistorized battery-driven, coupled pulse generatort (Fig. 2) was used for all subsequent experiments.
N
METHODS
GAGE,
AND MATERIALS
The method, at least in our hands and in its most consistently effective form, involves the introduction of a premature ventricular depolarization, If the latter occurs early enough in the cardiac cycle, no detectable contractile response is elicited by it. This electrical event is followed by a compensatory pause. If the first stimulus of the next pair is then fired before termination of this pause, the effective mechanical rate of the heart can be slowed to close to 50 per cent of the inherent rate or to any lesser degree. The pattern obtained by the paired stimuli resembles cer-
t Designed and manufactured Minneapolis, Minn.
by Medtronic,
Inc.,
* From the Departments of Surgery and Medicine, Veterans Administration Hospital, Buffalo, N. Y., and the State University of New York at Buffalo School of Medicine. This study was supported in part by a grant-in-aid from the Heart Association of Erie County, Inc., Buffalo, N. Y. 374
THE AMERICANJOURNAL OF CARDIOLOGY
Paired
375
Pulse Pacemaking
FIG. 1 (Experiment 20). A, left ventricular pressure (calibration: 25 mm. Hg per division). B, electrocardiogram. Spontaneous bigeminal arrhythmia observed in an anesthetized dog prior to any electrical stimulation. In cycles 2, 3 and 4 (from left to right), the extrasystole occurs relatively late (240 msec.) and produces a weak but significant extrasystole. In cycles 5, 6 and 7, the extraIn cardiac cycle 1, it occurs still systole occurs earlier, and the pressure event is barely detectable. In electrical slowing of the heart, the optimal earlier (170 msec.) and no pressure event is discernible. time relationship seen in cycle 1 is reproduced sequentially by paired electrical pulses separated by a critical fixed interval. With ventricular driving, the second stimulus of a pair must be administered near to or in the period of vulnerability; and for this reason, pacemaker stimuli were kept to near-threshold value (usually between 1 and 2 milliamperes).
Figure 3. The panel on the left shows a sinus rhythm with an interval of 400 msec. between cardiac cycles. The heart was then driven (middle panel) from a left ventricular electrode with paired stimuli at an interval of 590 msec. between pairs and an interval of 225 msec. between the pulses of each pair. The second depolarization occurs too late and is followed by a pressure event which, although feeble, must entail some expenditure of energy. On the panel to the right, the rate between pairs of stimuli is the same, but the interval between the pulses of each pair has been reduced to 190
RESULTS For brevity of presentation, the experiments performed have been summarized in Table I, and representative records have been selected to illustrate the most important aspects of this technic : (1) Ventricular Driving: This is illustrated in TABLE
Summary Experi“lent Dog No.
Sinus Rate
SlOWd Rate
Driving Site
146-167 167-187 134 108
86-115 115-120 96 86
LV LV LV LV
5 (396)
111-146
86-120
LV
6 (359) 7 (380)
166 167
120 111
LV LV
150-158 150 250 120
115-120 104-107 167 107
LV LV, RA LV
12 (417)
1.50
90
LA,
LV
t
13 (403)
130
88
RA,
LV
=
1 2 3 4
8 9 10 11
(384) (391) (392) (396)
(413) (408) (406) (414)
= = LA
107
LV
100 115 88
RA, LV, RA,
LV RA LV
18 (419) 19 (426) 20 (428)
177 162 150
109 79 100
RA, RV, LV,
RV LA RA
SEPTEMBER
Preliminary experiment Preliminary experiment Heart size recorded with induction coils VF following atropine & isoproterenol to increase sinus rate VF following z&opine & auricular loading with cold saline. Intramural P recorded Arch strain gauge on left ventricle Minor changes in mean flow in anterior descending coronary artery. See text Ascending aorta flow. See Figure 10 Atria1 tachycardia, electrically induced Spontaneous VT and spontaneous reversion to sinus tachycardia. See Figure 11 Coronary air embolization to produce acute left ventricular failure. Increase in LVP probably due to catheter artefact
VF following ligation nary artery
= = =
of anccrior
descmding
core-
Developed AF after atria1 driving Contmlled by ventricular driving. Also atria1 loading experiment. See Figure 6
zc
= =
= =
= left atrium; RV = right ventricle; fibrillation; AF = atria1 fibrillation;
1964
=
4 =
=
187
Comments
(LAD)
i
150 154 143
14,
Coronary Flow
4
14 (404)
VOLUME
LVP (Mean)
i
15 (427) 16 (405) 17 (434)
LV = left ventricle; LA pressure; VF = ventricular
I
of Experiments
RA
=
= =
Minor Minor
changes changes
in coronary in coronary
right atrium, AP = ascending aorta pressure; unchanged or insignificant changes; and LAD =
flow. flow.
See Figure
8
LVP = left ventricular left anterior descending.
Clllarclack.
376
INTERVAL
COUPLED-PULSE
-20
--
--
--.__L____
WIDTH
GENERATOR
Gage
and Ijean IIMC. No pressure rvcnt is then discernible following the second depolarization. (2) Myocmdial Confrac-tilif,:: Two of the experiments attempted to answer the following questions: (a) Does the second depolarization occur before the myocardium has recovered contractility, or (hj Is there, in fact, contraction of a significant number of fibers which escapes detection either because of asynchrony. or because of lack of sensitivity of the transducers in use? In the first of these experiments, ventricular contraction was recorded by an arch strain gauge sewed onto the surface of the left ventricle. Inspection of the strain gauge tracing fails to reveal any contractions that are not also seen on the left ventricular pressure record (Fig. 4). In a second set of experiments, intramyocardial pressure was recorded by connecting two polyethylene tuhes hy a 1 cm. long sleeve of collapsible, silicone rubber tubing. This segment was threaded into the depth of the left ventricular myocardium so that the stiffer polyethylene tubes were situated at both exits of the tunnel. The systrin was filled with saline and connected to the two ends of a transducer. The pressure in the tubes was adjusted to obtain pulsatile pressure recordings.
PRESSURE lEFT ATRIUM
200 PRESSURE AORTA
-
200 PCESSURI!
LEFT
VENTRICLE 0
ECG LEA0 2
ECG AURICULAR LEAD FIG. 3 (Experiment 15). Sinus rate (left) is 150 beats per minute; was slowed to 100 beats per minute by paired Compare optimal interval of 190 msec. (right) with less satisfactory timing (225 stimuli delivered to left ventrick. msec.) in the middle Fanel, followed by a slight but demonstrable second ventricular pressure event. No such event is discernible on the right panrl. THE
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Paired
Pulse Pacwnakin~
c.---I40 1, PRESSURE tEFT . VENTRICLE -----0
y------
140
PRESSURE AORTA
0 I’( , 3
STRAIN GAUGE
I
ECG
PAIRED STIMULI FIG. 4 (Experiment 6). Tracing obtained during slowing of the heart by paired stimuli delivered to the left ventricle. Two interspersed conducted beats (at A and B) have occurred before arrival of the first stimulus of a pair. As a consequence. the second depolarization of that pair is less premature than in the other cycles and leads to a discernible contraction. The latter is well defined as a separate contraction on the arch strain gauge trace. but it is also revealed on the left ventricular pressure trace by a slight change in contour.
It was thought that this technic might reveal asynchronous contractile events of some myocardial fibers in the vicinity of the compressible segment; however, inspection of the tracings fails to reveal any interruption of the smooth contour of the declining pressure during relaxation (Fig. 5). (3) Role of Left Ventricular Filling: Several experiments were designed to evaluate the role played by the degree and the rate of left ventricular filling. It was postulated that if a high rate of ventricular filling were made to prevail, the second depolarization might produce a separate discernible ventricular pressure event. The left atrium was cannulated with a large bore catheter (No. 30 French) connected to an elevated (50 cm.) reservoir of saline, and the flow of saline into the auricle was recorded with an electromagnetic flowmeter. In other runs, the ascending aorta was partially or completely occluded for a few beats. In several VOLUME
14,
SEPTEMBER
1964
runs (Fig. 6), both maneuvers were combined. The aorta was clamped and the reservoir opened. ,4lthough immediate filling and stretching of the ventricle must occur under these circumstances, the second stimulus of the pair was not followed by a separate contraction. (-I) Auricular Driving: Control of the heart rate could also be obtained by paired stimuli delivered to either auricle (Fig. 7). Adjustment of the rate and of the interval was more difficult with this modality. Placement of the electrodes on the auricle was critical because of the proximity of the phrenic nerve. If the latter is in the current field of the electrodes, synchronous contractions of the diaphragm are produced. (5) Coronary Blood Flow: In experiments on 3 animals, flow in the anterior descending coronary artery was recorded with an electromagnetic flowmeter (Fig. 7 and 8). Inspection of the record of pulsatile flow during sinus rhythm
378
PktSSURt ,NTRA-
JL,~%
: i ‘jim
MYOCARDIAL
.
.,
,
.~
I
VENTRICLE __--~~~
-O-
FIG. 5 (Experiment 5). Recording of intramyocardial pressure during slowing of the rate (cycles 1, 2 and 3, left to right) shows no evidence of myocardial contraction with the second depolarization.
FLOW
LEFT ATRIA1 CANNULA
PRESSURE AORTA
200 PRESSURE LEFT VENTRICLE
ECG
AND PAIRED STIMULI
FIG. 6 (Experiment 17). Slowing of the heart by paired pulses. At A, aorta was clamped. At B, saline Left ventricular pressure events continue at the rate of one conreservoir was emptied into atrium. traction for each two depolarizations. THE
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Paired
Pulse
Pacemaking
PRESSURE AORTA
FIG. 7 (Experiment 7). The rate slowed to 111 beats per minute (left of vertical intercept) from 167 beats per minute by pairs of stimuli applied to auricle. Coronary flow (uppermost trace) continues throughout long diastole. Paper speed: 100 mm./sec.
shows the characteristic pattern of forward flow throughout the cardiac cycle but with a sharp reduction of the flow rate during systole. When the heart was slowed, coronary flow continued at high rates during the long diastole with only a slight decline during end-diastole, paralleling the fall in diastolic filling pressure. Forward flow during systole was more reduced during slowing, probably because of the greater forcefulness of the potentiated contraction. Peak flow rates were lower when the heart was slowed. Mean coronary flow most often remained unchanged when the heart was slowed (Fig. 7). In some runs it increased slightly, and in others a decrease was noted at the lower rate. These changes were small and mostly paralleled the slight changes and fluctuations of the blood pressure which occurred when the rate was artificially slowed or when it was permitted to return to sinus rhythm. (6) The Effect of Single Pulses: Numerous attempts to slow the heart electrically without producing two depolarizations for each contraction were unsuccessful. In a few experiments, using single pulses of 170 msec. duration, a slowing effect was seen in an occasional cardiac cycle, but it was not possible to obtain this effect In other runs, using pairs of stimconsistently. uli, the effect could be produced in every cycle, but slowing of only a minor degree (approximately 10%) could be obtained (Fig. 9). VOLUME
14,
SEPTEMBER
1964
(7) Hemodynamic Effectr of Slowing of Rate: Several experiments yielded information on the beneficial effects that can result from slowing of rates which were sufficiently rapid to induce adverse hemodynamic alterations in the animal. In 1 dog, atria1 tachycardia was produced by driving the atrium at 250 beats per minute from a separate pacemaker. The ventricular rate was then slowed to 160 by pairs of pulses delivered through a ventricular electrode; this resulted in significant improvement of the aortic pressure. In another animal, moderate tachycardia with pulsus alternans spontaneously developed, probably due to myocardial depression from barbiturate anesthesia. When the heart was slowed (Fig. 10) from 158 to 115 beats per minute, blood pressure and cardiac output rose although left ventricular pressure work fell significantly. In one animal (Fig. 11) ventricular tachycardia occurred spontaneously prior to any Elecattempts at electrical control of the rate. trical reduction of the rate by 36 per cent was beneficial in terms of an augmented blood presthe ventricular tachysure. Subsequently, cardia converted spontaneously into a sinus tachycardia, and blood pressure levels achieved during sinus tachycardia, although better than those seen with ventricular tachycardia, were still clearly inferior to those obtained with artificial slowing of the heart.
Chardack,
380 -_
Gag-e and Dean
__-_-200
PRESSURE LEFT VENTRICLE
PRESSURE A0 RTA
ECG
60 CORONARY FLOW y0 FIG. 8 (Experiment 19). Rate slowed to 100 beats per minute from 150 by paired stimuli applied to the right ventricle. Mean aortic pressure is little affected except for fluctuations at the time of the change in rates. Mean coronary flow (left anterior descending artery) is slightly higher at the faster rate. Note also the difference in instantaneous flow rates. Mean left ventricular pressure rises sharply at the higher rate. A, zero flow, by momentary occlusion of artery downstream to flow probe. DISCUSSION
Our experiments show that paired electrical stimuli, appropriately timed, can consistently slow the effective mechanical rate of the heart. The second stimulus of each pair elicits a ventricular depolarization very early in the cardiac cycle when excitability has returned but when recovery of contractility has as yet not occurred. This technic leads to an increase in the number of electrical events but to a decrease in the number of mechanical contractions. The increase in the number of electrical events above the control sinus rate is inversely proportionate to the degree of slowing. A detailed comparison of our results with those obtained by Lopez et al.’ cannot be made at this time since the account of their findings has as yet not appeared in print. A personal communication2 from the authors indicates that at least some of their experiments dealt with the same mechanism of two depolarizations pro-
duced
for each
attempts
mechanical
contraction.
Our
to obtain slowing of both the electrical
and the mechanical
rate were largely unsuccess-
ful, and when they were consistently successful, only minimal slowing could be obtained. It may well be that in this regard their experiments were more rewarding. In any event, the data so far obtained indicate that the rate of apparent ventricular contractions can be reduced to close to 50 per cent of the sinus rate. This can be accomplished with surface or endocardial electrodes from any of the four cavities. .4uricular driving was more difficult but has the obvious advantage of preserving normal atrioventricular synchronization and ventricular activation. Stimulation of the atrium should also be safer than ventricular driving since the stimulus, although premature, travels through the normal conduction system and is of physiologic amplitude. While this modality may THE
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Paired Pulse Pacemaking
FIG. 9. A. Experiment 5. Tracing shows that the second stimulus does not evoke a propagated response (cycles 1 through 4 from left). However, the rate is slowed to only 86 from the control sinus rate of 96 (cycles 5 through 9). Paper speed: 50 mm./sec. B, Experiment 2. Long pulses produce depolarizations at make and at break. In cycle 2, from left. the break fails to evoke a propagated response. The rate is 120. Control sinus rate was 187. Paper speed: 100 mm./sec.
lead to auricular fibrillation, on theoretic grounds, it should be less prone to provoke ventricular fibrillation. In practice, although a considerable number of experiments involved ventricular driving, ventricular fibrillation was observed in only a few instances and appeared to be related to the administration of drugs, interference with coronary circulation, and surgical manipulation of the heart. We gained the impression that ventricular driving with pulses of near-threshold amplitude appeared to be quite safe. This point is of crucial importance and requires further study and more specific documentation. Intracavitary and intramyocardial pressure recordings as well as arch strain gauge measurements indicate that either no contraction accompanies the second depolarization or that it is of insufficient amplitude to be detected by the measuring devices employed. These studies do not rule out completely the possibility that a significant number of fibers do contract but that their conVOLUME
14,
SEPTEMBER
1964
traction remains hidden because of asynchrony. Whether the second depolarization and the nonapparent mechanical contractionif it exists-entail a significant expenditure of energy also remains to be determined. The time relation between recovery of excitability and that of contractility is such that, in the dog, an interval of approximately 50 msec. is available for optimal placement of the second stimulus of the pair. The adjustment of the interval between pulses is critical and has been difficult to achieve on the basis of the electrocardiogram alone. A longer than optimal interval between pulses leads to extrasystolic pressure events which, since they are not accompanied by ejection, must of necessity reduce the efficiency of cardiac work. For these reasons, at least in our hands and at the present time, paired pulse pacemaking requires continuous monitoring of the pressure in one of the ventricles. Mean left ventricular pressure was consistently reduced during slowing in spite of an augmented
382
(ihardack,
Gage and 1l)ean
2500 MEAN
FLOW AORTA 0
PRESSURE AORTA
100 PRESSURE LEFT VENTRICLE 0
ECG
PAIRED STIMUll
FIG. 10 (Experiment 8). Tracings show effect of slowing of the heart on ascending aortic flow (cardiac output minus coronary flow) and on aortic pressure. Sinus rate of 158 beats per minute was slowed to 115 beats. Note The decrease in left ventricular diastolic pressure during slowing disappearance of pulsus alternans at slower rate. indicates enhanced contractility. Paper speed : 25 mm./sec. and 1 mm./sec. during recording of mean values.
systolic peak pressure. With increasing degrees of slowing, the decrease in the number of pressure events offsets and then outweighs the increase in the peak systolic pressure. Thus, the overall effect is a net reduction of the area under the left ventricular pressure curve per unit time. This area quantitatively describes the external pressure work, and the latter is one of the important determinants of coronary flow and oxygen consumption of the heart. Recor&ng$ uf mean coronary j?ow (in runs in which aortic pressure remained unchanged) did show a slight decrease at the slower rate (Fig. 8) but in many runs, there was no change in mean coronary flow except during the brief periods of adjustment which followed a change of rate. In some experiments, mean coronary flow was slightly higher at the slower rate. All in all, these changes in mean coronary flow were
surprisingly small in view of the very marked reduction observed in mean left ventricular pressure produced by slowing of the heart. Studies of tfle pulsatile coronary jowl during electrical slowing show the entire diastolic interval to be available for flow. It is possible that this long diastolic interval alters the regulatory mechanism of coronary flow, and this might explain the minor changes observed in mean coronary flow contrasting with the marked change in left ventricular pressure work. The observation that peak coronary flow rates were always lower, and in some instances markedly so, at the slower rate would support such an explanation. The mechanism of regulation of coronary flow is still a matter of debate, but there is increasing agreement that myocardial metabolic activity and oxygen consumption play an important part in it and that whenever energy THE
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Paired
Pulse
Pacemaking
PRESSURE AORTA
100
~
PRESSURE RIGHT VfNTRlCtE 0
ECG
FIG. 11 (Experiment 11). A, sinus rhythm at beginning of experiment (rate 120). B, spontaneous ventricular tachycardia prior to any electrical stimulation (rate 167). C, same as B, a few minutes later. Shows pulsus alternans (rate 158). D, improvement in pressure with slowing by paired pulse stimulation (rate 107). E, same as D, a few minutes later (rate 107). F, return to ventricular tachycardia on withdrawal of electrical stimuli (rate 134). G. spontaneous reversion. a few minutes later, to normal sinus rhythm (rate 134). Paper speed : 25 mm./sec. in panels A through D ; 10 mm./sec. in panels E, F and G.
expenditure outruns oxygen supply, intravascular resistance decreases and leads to an increase in coronary flow. The lower coronary flow rates observed when the heart was slowed would indicate a higher level of intravascular resistance and suggest that, although total coronary flow at the slower rate is not changed, the myocardium operates on a more favorable metabolic level. Because of the long diastolic interval at the artificially slowed rate, lesser flow rates This are required to yield a given mean flow. alteration in the diastolic time-flow relation may well be of significance when coronary flow rates are limited by the presence of obstructive coronary arterial disease. On the other hand, it is also possible that the second depolarization and the potentiation of the beats which occurs with electrical slowing entail significant energy expenditures and tend to raise coronary fiow requirements. These observations are fragmentary and based on relatively few experiThey require further substantiation ments. particularly in conjunction with determinations of oxygen consumption. Such studies are now in progress. Some degree of postextrasystolic potentiation was observed in all our experiments with paired VOLUME
14,
SEPTEMBER
1964
pulse pacemaking. It was manifest by an increase in peak systolic pressure and the greater forcefulness of the postextrasystolic contraction was also evidenced by a steeper rate of change of the ascending limb of the left ventricular pressure curve. A recent study by Siebens et a1.3 dealt in detail with this phenomenon, and some of their observations are relevant in this context. The greater the prematurity of the extrasystole, the weaker is the left ventricular pressure event produced by it. Also, the strength of a postextrasystolic contraction is always enhanced by comparison with preceding normal cardiac cycles, and this potentiation increases as a linear function of the prematurity of the extrasystole. In paired pulse stimulation, the prematurity of the extrasystole is such that the resultant contraction is either absent or cannot be measured, and since enhancement of the postcompensatory beat increases with extrasystolic prematurity, paired pulse stimulation entails maximal potentiation obtainable by prematurity. Siebens also showed that potentiation was affected by the interval elapsed between an a postextrasystolic-driven extrasystolic and beat and was maximal when the interval ap-
pwxinlated OIW and one-half’ cardiac c\~les. These observations arc pertinent to electrical slobving of the heart because the interval referred to corresponds to that between the second stimulus of a pair and the first of the following one. This suggests that maximal potential+ effects can be expected at the maximal rates of slowing obtainable with this technic, that is, at rates between SO and 60 per cent of the control sinus rate. Our clinical rxfwience with laired pulse ~nc-rmaking is limited, but the few observations made so far in the course of thoracotomy have established that the technic is applicable to the -4 discussion of its clinical uses human heart. is beyond the scope of this report except to suggest that cardiac catheterizations and postcardiotomy states come to mind readily as an area in which prudent evaluation of the technic could be initiated. This would entail only the leaving behind of a myocardial electrode wire and an intraventricular, small-diameter catheter, which subsequently can be withdrawn. Both technics have been used clinically and would permit slowing of the heart with constant monitoring of the right ventricular pres,4 controlled reduction of the heart rate sure. may be of value in postcardiotomy sinus tachycardias which cannot be adequately subdued by drugs. These are but a few clinical situations in which this technic might be explored and such studies are now in to advantage. progress.
depolarization occurs wit11 both stiiuuli of tlic pair, but no measurable contraction follows the second stimulus. Slowin,g of the heart by this technic leads to (a) a decrease in mean left \,entricular pressure? (b) a potentiation effect, and (c) higher cardiac output and blood pressure when used to correct tachycardias severe enough to produce adverse effects on these parameters. When the heart is slowed electrically, coronary flow continues throughout the long diastolic period. This technic has been used successfully in man in the course of thoracotomy. ADDENDUM Since submission of this manuscript, a personal communication from .J. F. Lopez indicates that a report on his studies entitled “Slowing the Heart Rate in Dogs by Artificial Electrical Pacing” is now in press in Circulation Research. Also, recent studies from our laboratory show that the sustained postextrasystolic potentiation produced by paired pulse stimuIation leads to a very significant increase in coronary tlow and oxygen consumption per beat. However, in regard to coronary flow and oxygen consumption per minute, this effect is offset in proportion to the reduction in rate. A detailed account of these studies is now in preparation. REFERENCES 1. I,DPEZ, J. F.,
A. and KATZ, L. N. Slowing of the heart rate by artificial electrical stimulation with pulses of long duration in the dog (Abstr.). EDELIST,
Circulation, 28: 759, 1963.
The rate of apparent ventricular contractions can be slowed by paired electrical stimuli separated by an interval of 150 to 250 msec. and applied to either ventricles or auricles. A
A. Personal communication. 3. SIEBENS, A. A.? HOFFMAN, B. F., CRANEFIELD, P. F. and McC. BROOKS, C. Regulation of contractile Am. J. force during ventricular arrhythmias.
2.
EDELIST,
Physiol., 197: 968, 1959.
TZIE AMERICAN JOURNAL OF CARDIOLOGY