A stimulator control unit for use in cardiac research

J. ELECTROCARDIOLOGY, 4 (3) 231-239, 1971

A Stimulator Control Unit for Use in Cardiac Research* BY LEO F. WALSH, WILLIAM J. MUELLER, AND MARY JO BURGESS, M.D.~

SUMMARY Digital integrated circuits were used to construct a unit to provide precise and flexible control in the generation of stimulus patterns required for investigation of cardiac physiology. The use of low cost and reliable integrated circuits allowed the design of a complex unit providing the experimentor with versatile stimulus patterns not previously available. This paper describes electronic circuit particulars, and descriptions of various modes of instrument operation. Illustrations are included showing circuit details and electrograms resulting from selected stimulus patterns.

effects of multiple successive premature beats, and the effects of complex, but precisely controlled, patterns of unequal cycle lengths could be investigated. Limited data of this type have been obtained with a specially designed stimulator 5"8, and indicate the importance of further studies in which controlled irregular cardiac rhythms are produced. This report concerns a new stimulator control system in which basic stimuli, $1, and premature stimuli, Su through ST, are generated. The six premature stimuli can be delivered after every basic stimulus or the instrument may be set so that up to twenty basic stimuli m a y be delivered before the premature stimuli are generated.

INTRODUCTION Many investigations of cardiac physiology require control of the heart rate and rhythm, and this is usually accomplished by electrical Stimulation. Stimulators are commerciaUv available which provide regular, and a limited variety of irregular pulse patterns. More precise and flexible control of stimulus patterns would permit new observations concerning the role of cardiac rhythm on electrophysiologic parameters and cardiac mechanics. For example, hemodynamic and electrophysiologic

*From the Department of Bioelectronics and Computer Sciences, and Department of Medicine, State University of New York, Upstate Medical Center, Syracuse, New York. This study supported by Public Health Service Grant GM-11413, HE03241, and 5T01 HE05628, and by General Medical Research funds of the Veterans Administration. tPresent address: Department of Medicine, College of Medicine, University of Utah, Salt Lake City, Utah 84112. Reprint requests: Leo F. Walsh, State University of New York, Upstate Medical Center, 766 Irving Avenue, Syracuse, New York 13210.

GENERAL D E S C R I P T I O N Fig. 1 is the block diagram of the instrument showing the system logic. Experience has shown that integrated circuits, by reason of their low cost and dependability, make ideal components for the construction of specialized instruments. All logic gates and flipflops used in the design were Motorola M E C L 13 integrated circuits.

Timing Circuits A logic gate wired as a 100kHz crystal oscillator I provides pulses at 10 usec intervals for driving the timing circuits. Pulses from the oscillator have an interval accuracy greater than 0.1% and are used as input to the timing circuits. The timing circuits are a series of six decade counters 4 with all but the first having ten line 0 to 9 decoded output. This 0 for 9 decoded output from the decoded decade units is brought through a ten position front panel switch to the input of a logic gate ~. Each of the five decade counters is wired through a switch to one of the inputs of this logic gate. The logic gate, shown in

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Fig. I. Block diagram or system logic. Switch S2a-f is the mode switch and is shown in the interpolated mode position, center position is independent mode and lost position is dependent mode. Switches $3-8 disable associated delay units. Switch $11 Automatic-Manual switch shown in Automatic position. Switch S14 Right ($2.4) - - Left ($5_7) switch shown in the center nonoperating position. Switch S12 S1 Single-S 1 Double shown in single position. Fig. 2, is wired for the "and" function. By using the switches to select the proper output from each of the decade units, the logic gate can be caused to switch logic levels at the precise interval that has been selected by the operator.

$1 Control Circuits This logic level shift has two functions. It resets the timing circuits to allow the correct starting point for the next interval, and it operates, Fig. 2, a monostable multivibrator pulse generator 9. T h e pulse generated is amplified by the interface units, Fig. 4, and used to drive the $1 stimulator. With the system as it is wired, a stimulus pulse can be gen-

crated at intervals of 1 msec to 9999 msec in increments of 1 msec and can be selected with accuracy of better than 0.1%. Another decade counter with decoder counts the number of basic stimuli ($1) delivered. T h e output of this decade counter decoder is wired to a front panel switch. This switch allows the operator to select the number of $1 stimuli to be delivered before initializing the interval during which the premature stimuli, $2 through $7, are to be delivered. U p to six premature stimuli can be delivered during this interval.

S~-$7 Control Circuits T h e number of pulses to be delivered is J. ELECTROCARDIOLOGY.VOL. 4, NO. 3. 1971

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one set of five switches for each of the six premature stimulator delay generators. Each set of switches has its c o m m o n pole wired to a five input logic gate, Fig. 3, wired for "and" operation. W h e n the input conditions to the logic gate are alI at the proper value, the logic gate output switches levels. This level shift is used to reset the delay bi-stable multivibrator. T h e same action causes a pulse generator to generate a pulse that m a y be used to drive a stimulus generator. T h e other five premature stimulus delay circuits operate in a like fashion. Thus, a pattern of up to six premature stimuli can be delivered with a precise delay timed from $1. Front panel switches allow the delay to be set to times of 0.1 msec to 9999.9reset in increments of 0.1 msec and with an accuracy of 0.1%. These delays m a y be accurately reset at any time during the course of an experiment.

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MODES OF OPERATION T h e instrument has three modes of operation, interpolated, independent, and dependent. Interpolated Mode. I n the interpolated mode the $2-$7 delay is referenced to the S~ stimulus occurring at the start of the premature interval, and the premature interval can exist only as long as the $I-$I interval. If $2-$7 delays in excess of the $I-$I interval are requested, they will not be delivered.

Independent Mode and Dependent Mode Inability to deliver premature stimuli with delays in excess of the S~-S1 interval could be

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APPLICATION Figs. 5-7 are electrograms taken to illustrate the application of the modes of operation and features of the stimulator to cardiac research.

Interpolated Mode The interpolated mode of operation is illustrated in Fig. 5. In part A, an electrogram is shown of a dog's spontaneous rhythm. The electrogram was taken at a paper speed of 100 mm/sec. A unipolar electrode was placed on the epicardial surface of the right ventricle, and the indifferent electrode on the left leg. J. E L E C T R O C A R D I O L O G Y , VOL. 4, NO. 3, 1971

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I n part B, unipolar stimuli were delivered to the left ventricle with an $1-$1, interval of 410msec, a n d the electrogram recorded as in part A. T h e same a r r a n g e m e n t of electrodes a n d $1-$1 interval were used in the other parts of this figure a n d Figs. 6 a n d 7.

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Fig. 5. Electrograms from a dog taken at a paper speed of 100 mm/sec. An unipolar electrode was placed on the right ventricle and the indifferent electrode was placed on the left leg. Part A shows the dog's spontaneous rhythm. Parts B through F illustrate the interpolated mode of stimulator operation. Basic driving stimuli were delivered to the left ventricle with an Sa-81 interval of 410 msec. The same basic driving rate, electrode arrangement and paper speed were used in recording the electrograms shown in Figs. 7 and 8. In part B, each S] is followed by a ventricular response. Premature stimuli were not introduced. In part C a premature stimulus, S~, was delivered 200 msec after other St ; and in part D, a premature stimulus, Sz, was delivered 200 msec after every fourth St. In both cases the S~-St interval was uninterrupted and the premature stimuli fell within the S1-St cycle length. In both E and F two premature stimuli, S~ and Sa, were delivered after every other Sa. S~ was delivered 200 msec after S1 and in both cases produced a ventricular response. In part E, S~ was delivered 300 msec after S~, and did not produce a ventricular response because the ventricle was stil] refractory after its response to S~. The next 81 occurred at its expected time 110 msec after Sa and its also produced a ventricular response. In part F, Ss was delivered 330 msec after S~, and in this case the ventricle had sufficient time to recover after its response to S~, and S~ also resulted in a ventricular response. However, when S~ was delivered 100 msec after $3, the ventricle was refractory after its response to S~, and S1 did not produce a ventricular response. In all examples in the illustration, the premature stimuli fell within the S1-St interval and did not interrupt the S~ rhythm. J. ELECTROCARDIOLOGY, VOL. 4, NO. 3, 1971

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I n part B, the stimulus artifact can be seen preceding each Q R S complex. T h e difference in form of the Q R S complexes in parts A a n d B reflects the change in the ventricular activation sequence. I n part C, a premature stimulus, $2, was delivered 200 msec after every second Sa, a n d in part D, $2 was delivered 200 msec after every fourth $1. T h e premature stimuli did not interrupt the S1-S1 intervals, a n d this mode of operation resulted in interpolated premature extrasystoles. I n parts E a n d F, two p r e m a t u r e stimuli, S~ a n d $3, were delivered after every second $1. I n part E, $2 was delivered 200 msec after $1, a n d resulted in a n extrasystole. $3 was delivered 300 msec after $1, but did not produce a n extrasystole because the ventricle was still refractory following its response to 82. W h e n the next $1 was delivered 110 msec after $3, the ventricle had recovered and responded to St. I n part F, $2 was again delivered 200 msec after $1, a n d resulted in an extrasystole, b u t Ss instead of being delivered 300 msec after $1 was delivered 330 msec after S~. T h e ventricle had sufficient time to recover after its response to $2, a n d $3 also produced a n extrasystole. However, when S~ was delivered 80msec after S~, no response occurred because the ventricle was still refractory after its response to Ss.

Dependent Mode T h e dependent mode of operation is illustrated in parts A-E of Fig. 6. T h e electrode a r r a n g e m e n t a n d St-S1 interval are the same as those used in Fig. 5. I n part A, 83 was delivered 200 msec after every other St, a n d the next $1 occurred 410 msec, one St-S1 interval, after S_~. T h e ventricle responded to each stimulus. I n part B, S~ was delivered 100msec after every other St, found the ventricle refractory, a n d did not result in a n extrasystole. T h e next St was still delivered 410 msec, o n e S t - S 1 interval, after S,. I n part C, two premature stimuli, $2 and S~, were delivered after every other $1. $2 was delivered 200 msec after $1 a n d produced a ventricular response; $8 was delivered 320 msec after $1, found the ventricle refractory from its response to $2, a n d did not produce a response. However, Sa still resets the timing circuits so

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Fig. 6. Electrograms from a dog. The same recording procedure was used as that used in Fig. 6, and the Sz-S x interval was 410 msec. Parts A through E illustrate the dependent, and parts F and G the independent modes of stimulator operation. The electrogram in part H was recorded at a paper speed of 50 mm/sec. In part A, one premature stimulus, $2, was delivered 200 rmec after S~. S 2 reset the timing circuits, and the next S t was delivered 410 msec, one Sz-S z interval, after S 2. In part B, S 2 was delivered 100 msec after Si, found the ventricle refractory, but still reset the timing circuits to deliver the next S t 410 msec after S 2. In part C two premature stimuli, S 2 and $3, were delivered 200 msec and 320 insec, respectively, after every other S~. S 2 produced a ventricular response, but S3 did not because it fell in the refractory period. In this case, Ss, the last premature beat of the train, reset the timing circuits; and the next S 2 occurred 410 msec after S 3. In parts D and E, three premature stimuli, $2, S 3 and 84, were delivered. In part D, the premature stimuli were delivered 300 msec, 550 msec, and 750 msec after S t. Each premature stimulus produced a ventricular response, and the next S t was delivered 410 msec one Sz-Sz cycle, after S 4. In part E, the premature stimulus settings were left as they were in part D with the exception of the S 2 setting which was adjusted to deliver S2 350 msec rather

than 300 msec after S r S 3 and S4 retained the same time relationship to S t that they had in part D. The timing circuits were reset by $4, and the next S 1 occurred 410 msec after S4but did not produce a ventricular response because it fell in the refractory period of an escape beat. Parts F and G illustrate the independent mode of operation. In part F, S 2 was delivered 300 msec after St, S 3 250 msec after $2, and S4 200 msec after S 3. These settings produced the same pattern of stimuli used in the dependent mode of operation illustrated in part D. The timing circuits were reset by the last premature stimulus as they were in the dependent mode of operation, and S t was delivered 410 msec after S 4. In part G, S 2 was delivered 350 msec after S t instead of 300 msec after StThe other premature stimulus settings were left as they were in part F. The alteration of the S 2 stimulus delayed not only S 2 by 50 msec, but also delayed S 3 and S 4 by 50 msec. This is because in the independent mode of operation a premature stimulus is timed from the stimulus immediately preceding it rather than being timed from S t . This is in contrast to the dependent mode of operation in which alteration of the setting of one premature stimulus does not affect the time relation of succeeding premature stimuli to S t. The electrogram shown in part H was taken at a paper speed of 50 mm/sec. Six premature stimuli were delivered at 200 msec, 500 msec, 750 msec, 1025 msec, 1400 msec, and 1590 msec, respectively, after every S t. The S~-S1 interval remained 410 msec. This electrogram illustrates the complex patterns of stimulation possible with this system. t h a t t h e n e x t $1 w a s d e l i v e r e d o n e S1-St int e r v a l a f t e r $3. I n p a r t s D a n d E, t h r e e p r e m a t u r e stimuli, $2, St, a n d $4, w e r e d e l i v e r e d . I n p a r t D, $2 w a s d e l i v e r e d 300 m s e c a f t e r $1, S~ was d e l i v e r e d 550 m s e c a f t e r St, a n d $4 was d e l i v e r e d 7 5 0 m s e c a f t e r $1. A f t e r t h e t r a i n of p r e m a t u r e s t i m u l i w a s d e l i v e r e d , t h e n e x t St was d e l i v e r e d o n e S t - S t i n t e r v a l a f t e r $4. I n p a r t E, all of t h e p r e m a t u r e s t i m u l u s s e t t i n g s w e r e left t h e s a m e as t h e y w e r e in p a r t D , w i t h t h e e x c e p t i o n o f t h e $2 s e t t i n g w h i c h w a s set t o d e l i v e r $2 350 m s e c a f t e r $1 i n s t e a d o f 300 m s e c a f t e r $1. T h e a l t e r a t i o n o f t h e t i m i n g o f $2 h a d n o e f f e c t o n t h e t i m i n g o f Ss w h i c h still o c c u r r e d 550 m s e c a f t e r $1, o r $4 w h i c h still o c c u r r e d 750 m s e c a f t e r $1.

Independent Mode T h e i n d e p e n d e n t m o d e of o p e r a t i o n is ill u s t r a t e d in p a r t s F a n d G of Fig. 6. I n p a r t F, t h r e e p r e m a t u r e

stimuli, $2, S~, a n d $4,

w e r e d e l i v e r e d . $2 w a s set t o o c c u r 300 m s e c a f t e r $1, S~ set for 250 m s e c a f t e r $2, a n d $4 J. ELEETROCARDIOLOGY. VOL. 4. NO. 3. 1971

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set for 200 msec after Sa. As in the dependent mode, the next S~ occurred one S1-St interval after $4. This setting produced the same pattern of stimuli used in the dependent mode of operation illustrated in part D of this figure. I n part G, $2 was set to be delivered 350msec after St instead of 300 msec after S~; the remaining settings were left as they were in part F. I n the independent mode of operation, $3 and $4 are independent of S~. Therefore, when the timing of $2 was altered, $3 maintained its time relation to $2 rather than S~, and $4 maintained its time relation to $3 rather than $1. $2, $3, and $4 all occurred 50 msec later than they did in part F although only the setting of $2 was altered. This is in contrast to the dependent mode of operation illustrated in parts D and E in which an alteration of the timing of $2 did not alter the St-S~ interval or the S~-$4 interval. As illustrated in 6H, this stimulator control system can be used to deliver trains of up to six premature stimuli after every St. T h e premature stimuli may be set up in either the independent or dependent mode, and set to produce grossly irregular patterns which can be chosen to stimulate the pattern of ventricular responses to atrial fibrillation, Wenckebach phenomena, and other cardiac arrhythmias.

response. This mode of operation permits stimulation of the atria and ventricles with a time relationship approximating normal AV conduction time and reduces the possibility of retrograde AV conduction and atrial echoes when complex patterns of stimuli are delivered to the ventricles. Double Pattern Function Another front panel switch controls a circuit that in one position inhibits the last three delay generators. While these generators are inhibited, their delay pattern can be set. W h e n the switch is put in the other position, the pattern set on the last three delay generators will be delivered, and the first three delay generators will be inhibited. N o w the pattern for the first three delay generators can be set. At the desired time, the switch can again be changed to deliver this set of stimuli. T h e function is illustrated in Fig. 7B. T w o patterns of premature stimuli were chosen. With the first stimulation pattern, a premature stimulus, S_~, was delivered after every other Sa. With the second stimulation pattern, two premature stimuli, $2 and S~, were delivered after every other $1. $2 was delivered 200 msec after S, in both patterns of stimulation and in both cases resulted in I

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SPECIAL FUNCTIONS Double Pulse Function To add to the versatility of the instrument, special circuitry was added to permit delivery of $1 as a double pulse stimulus. This feature can be selected by a front panel switch which causes the first delay generator to operate after each St pulse. After the selected number of $1 doublets has been delivered, as m a n y as five premature stimuli m a y be generated. This function is illustrated in Fig. 7A. T h e S~-SI interval was 410msec, as in Figs. 5 and 6, but S~ was delivered as a doublet, S1A and SaN. S1B was delivered 200 msec after each S~A. After every fourth S~ doublet, an $2 was generated 320reset after SaA. $2 was delivered at a time when the ventricle was refractory and did not produce a ventrieular J. ELECTROCARDIOLOGY,

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Fig. 7. Electrograms taken to illustrate two additional modes of operation. In part A, S~ was delivered as a doublet, S1A and S1B. SaB reset the timing circuits so that S m occurs 410 msec, one St-S 1 cycle after Sxn. A premature stimulus was delivered 320 msec after every fourth S1A. In the example shown, S~ did not produce a ventricular response because the ventricle was still refractory after its response to SIB. In part B, two patterns of stimulation were set. One pattern, set on the first bank oI delay generators, delivered one premature stimulus, Sz, 200 msec after every other S 1. After S2 was delivered, the stimulator was manually switched so that the first three delay generators were inhibited, and the pattern of stimulation set on the second

bank of delay generators was delivered. The second pattern of stimulation delivered two premature stimuli, S2 and S~, 200 msec and 300 msec, respectively, after every other S1.

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a ventricular response. With the second pattern of stimulation, Ss was delivered 320 msec after S~ and did not produce a ventricular response because the ventricle was still refractory following its response to $2. The two patterns of stimulation were delivered without losing control of the cardiac rhythm during switching and setting times. CONVENIENCE FEATURES Several circuits are incorporated in the instrument which will aid the operator in setting up stimulus patterns and observing the results.

St Controls A set of three front panel switches allows the operator to remove the first, second, and third $1 stimulus pulses. These switches can be used to prevent Sa stimuli from interfering with spontaneously evoked activity caused by the premature stimuli. A numerical display tube keeps the operator informed of the number of $1 stimuli delivered and of the time when premature pulses are to be generated. One switch doubles the number Sj stimuli that can be delivered, and another switches the unit to manual operation. In the manual mode, the S~ stimuli are delivered continuously. If a volley of premature stimuli

is desired, the operator can operate a push button which will deliver one volley only. To deliver another volley of stimuli, the button must be pushed again.

Synchronizing Signals Various oscilloscope synchronizing pulses, Fig. 8, are available to conveniently and accurately observe the results of stimuli delivered from this instrument. Front panel switches allow the operator to synchronize the oscilloscope trace to any of the $1 pulses or any of the $2-S~ pulses.

Output Signals The instrument has six output signals. One output is used to synchronize an oscilloscope and the other five drive pulse generators, Fig. 4, such as the Tektronix 160 series. Five pulse generators are used to supply the stimuli. The amplitude and duration of the stimuli are determined by the control settings on these generators. Seven sets of five switches have been incorporated in the circuitry, Fig. 4, to allow the operator to select which stimulus generator is to be driven by which timing unit. This gives the operator the choice of delivering complex patterns of up to six premature pulses to as many as five sites.

CONCLUSION This new stimulator control unit, used in conjunction with five pulse generators, enables an experimenter to precisely and conveniently set up varied and complex patterns of stimulation for investigating the role of rate and rhythm on electrophysiologic parameters and cardiac mechanics. All delays and intervals are selected by switches. Synchronous signals that coincide with each of the stimulus pulses and the different modes of operation are also chosen by switches. The system permits an investigator to conveniently set up complex patterns of stimulation, to handily alter the stimulus program and to precisely and repeatedly reset stimulus programs during the course of an experiment.

Fig. 8. Schematic diagram of manual circuits, synchronous pulse generating circuit and logic used to control timing unit reset pulses in dependent and independent modes.

Acknowledgement: The authors express their appreciation to Mr. Edward C. Roberts and Ernest Andrews for technical assistance, Mrs. Julia Hammack for art work, and Mr. Lou Georgianna for photography. J. E L E C T R O C A R D I O L O G Y , V O L . 4 , NO. 3, 1971

STIMULATOR CONTROL UNIT

REFERENCES 1. Bytes, C. H. : Power your oscillator with ECL Electronic Design, August, 1968. 2. Garth, E.: System Design with MECL Integrated Circuit Logic Blocks. 3. Landers, G. H.: MECL Family of integrated circuits, Motorola application note AN-201. 4. Landers, G. H.: Designing Integrated Serial Counters, Motorola application note AN-194. 5. Mendez, C., and Moe, G. K.: Some characteristics of transmembrance potentials of AV nodal cells during propagation of premature beats. Circulation Res. 19:993, 1966.

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6. Moe, G. K., Abildskov, J. A., and Mendez, C.: Experimental study of concealed conduction. Am. Heart J. 67:338, 1964. 7. Moe, G. K., Mendez, C., and Abildskov, J. A.: Complex manifestation of concealed A-V conduction in the dog heart. Circulation Res. 1$:51, 1964. 8. Moe, G. K., Mendez, C., and Han, J.: Aberrant A-V impulse propagation in the dog heart: Study of functional bundle branch block. Circulation Res. 16:261, 1965. 9. Rewschler, E.: Design of monostable multivibrators using MECL integrated circuits, Motorola application note AN-233.