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Paired-pulse stimulation of the heart
American
Heart Journal February,
1966, Volume ?I, Number 2
Editorial
Paired-pulse
stimulation
Brian F. Hofman, M.D.* Paul F. Crane$eld, M.D., New York, N. Y.
Ph.D.
I
n the fall of 1963, Lopez, Edelist and Katz’ pointed out that if the heart were to be driven electrically in such a way that every regular beat were followed by an early premature beat, the early premature beat would be essentially mechancially ineffective. Under such conditions, they suggested, the electrical rate of the heart would be twice as great as the rate of effective mechanical contractions. The presence of two complete cycles of electrical activity for each cycle of mechanical activity might, they reasoned, suppress ectopic beats and control tachycardias. This line of investigation was pursued by Katz and his co-workers and by Chardack and his co-workers, and later by Braunwald and his co-workers. It was also pointed out by Hoffman, Cranefield, and their co-workers that this form of artificially induced arrhythmia would of necessity induce the enhancement of force of contraction known as postextrasystolic potentiation, and they showed that such maintained postextrasystolic potentiation can reverse all of the features of acute heart failure in dogs. From the Department of Pharmacology, Received for publication May 7, 1965. *Address: Department of Pharmacology. St., New York. N. Y.. 10032.
143
of the heart
College College
During the past 18 months extensive investigations of many aspects of this phenomenon have been carried out on animals and on patients. A conference was held on the subject in January, 1965, and the 22 papers delivered have appeared in the May and June, 1965, issues of the Bulletin of the New York Academy of Medicine. It is possible, therefore, to offer a summary of the present status of this method. Technically, it is fairly simple to induce the desired alteration in cardiac rhythm. Any of the types of electrodes used for ordinary electrical pacemaking of the heart may be employed. Special stimulators for delivering pairs of stimuli have been made available commercially, and with suitable precautions various standard physiologic stimulators may be used. There are many precautions which must be observed with respect to isolation of the stimulators, with respect to juxtaposition of the electrodes to the myocardium, and with respect to the strength and duration of the stimulus. These precautions are discussed at length in the of Physicians of Physicians
and and
Surgeons, Surgeons,
Columbia Columbia
University, University.
New
York,
N. Y.
630
West
168th
proceedings of the conference referred to above. Several cases are no\\’ known in \\,hich the use of paired-pulse stimulations has successfully controlled tachycardias which had proved to be resistant both to drug therapy and to countershock. In one such case a ventricular tachycardia with it downhill course was controlled (the electrical rate remaining high, but the effective mechanical rate being half that of the electrical rate). In that case, pairedpulse stimulation \vas discontinued after 2 days and the tachycardia had subsided. In another case, paired-pulse stimulation n:as employed for 30 days to reduce the effective mechanical rate in a seriously ill patient \\-ho eventually died. In spite of the eventual death of the patient, pairedpulse stimulation was the only means tvhich succeeded in slowing an extremely ominous Life-threatening tachycardia. tachycardias lt:hich are wholly resistant to drug therapy and countershock are as suitable rare but may- be regarded for treatment by paired-pulse stimulation, provided that it is used with the requisite skill and understanding. Paired-pulse stimulation, by producing maintained postextrasystolic potentiation, can greatly enhance the force of contraction of the ventricular myocardium in states of acute cardiac failure. Severe acute heart failure caused (in animals) by outflow constriction, by beta-adrenergic blockade, or by difficult and delayed deimproved by fibrillation is decisively paired-pulse stitnulation during a period in nhich death from cardiac failure \vould otherwise have ensued. Such animals returned to normal cardiac function after cessation of paired-pulse stimulation in experiments in which the cause of the acute heart failure was removed. Clinical experience with the inotropic effects of paired-pulse stimulators is far more limited at present. In a single case, paired-pulse stimulation has been applied continuously for 13 days in a patient with chronic heart failure, in an effort to bring the patient to a level of function sufficient to permit replacement of a valve. The objective signs of improvement in this case bvere slender and the patient did not improve enough to permit operation. The
patient did show nwked subjective 1111. provement and there \vere no serious WII~-plications secondar!. to the use of tht technique. Zo other c;~cs in \\ hich t hc technique WE employed to relieve heart failure have Ixxn reported Among the problems and hazards associated with this inethod are the danger of evoking arrhythmias (in particular ventricular librillation) and the problerti of M:hether the technique causes an increase in the oxygen demands of the myocardium. It R’X clear that the technique can bc used in both animals :ind human beings \\ithout evoking dangerous arrhythmias: it is also clear that faull?~ use of the technique or its use in certain not y.et full!. defined clinical states rl~a!r result in such arrhythmias. No agreement has beeri reached on the problem of the effect of paired-pulse stimulation on the oxygen demands of the myocardium. (-ertain evidence suggests that there is a significant increase. Other evidence sugg-ests that a concomitant increase in coronary arter!. flow Maya compensate for any increased needs for oxygen. It has also been suggested that the increased eilicienc!, of contraction ma!’ actually lessen the needs for oxygen. It is universally agreed that the technique and the wide variety of effects which it produces in the heart raise a host of questions of great importance to cardiac physiology and clinical cardiology. These questions are under investigation in man)’ clinics and laboratories. It is also agreed that the enhancement of the force of contraction and the antiarrhythmic effect of paired-pulse stimulation deserve careful but cautious clinical investigation. It is thought that the technique should be used, at present, only by persons familiar with the underlying physiologic principles, preferably chiefly b\. persons who have thoroughly familiarized themselves \vith its effects by studying it on animals, and chiefIy in clinical situations of an unquestionably life-threatening nature that have failed to respond to conventional therapy. The technique is niost emphatically in an investigative state; riian~~ questions its to its safety and value must be nns\cered. Nevertheless, it is possible that it will have genuine clinical value, and it has already
Volume Number
71 2
provoked many important experiments and a re-examination of many aspects of cardiac physiology. REFERENCES 1. Lopez, J. F., Edelist, A., and Katz, L. N.: Slowing of the heart rate by artificial electrical stimulation with pulses of long duration in the dog, Circulation 28:7.59, 1963. 2. Chardack, W. M., Gage, A. A., and Dean, D. C.: Slowing of the heart bv naired nulse pacemaking, Km. J. Cardiol. -lk:314, i964. 3. Scherlag, B. J., Yeh, B. K., and Cranefield P. F.: Effect of continuous postextrasystolic potentiation on the acutely failed dog heart, Physiologist 7:246, 1964. 4. Braunwald, N. S., Gay, W. A., Morrow, A. G. and Braunwald, E.: Sustained, paired elec-
Paired-pulse
stimulation
of heart
145
trical stimuli. Slowing of the ventricular rate and augmentation of contractile force, Am. J. Cardiol. 14:385, 1964. Cranefield, P. F., Scherlag, B. J., Yeh, B. K., and Hoffman, B. F.: Treatment of acute heart failure by maintained postextrasystolic potentiation, Bull. New York Acad. Med. 40:903, 1964. Lopez, J. F., Edelist, A., and Katz, L. N.: Reducing heart rate of the dog by electrical stimulation, Circulation Res. 15:414, 1964. Braunwald, E., Ross, J., Frommer, P. L., Sonnenblick, E. H., and Gault, J. H.: Clinical observations of paired electrical stimulation of the heart, Am. J. Med. 37:700,1964. Cranefield, P. F., editor: Conference on paired pulse stimulation and postextrasystolic potentiation in the heart, Bull. New York Acad. Med. 41:417, 1965.
Heart Journal February,
1966, Volume ?I, Number 2
Editorial
Paired-pulse
stimulation
Brian F. Hofman, M.D.* Paul F. Crane$eld, M.D., New York, N. Y.
Ph.D.
I
n the fall of 1963, Lopez, Edelist and Katz’ pointed out that if the heart were to be driven electrically in such a way that every regular beat were followed by an early premature beat, the early premature beat would be essentially mechancially ineffective. Under such conditions, they suggested, the electrical rate of the heart would be twice as great as the rate of effective mechanical contractions. The presence of two complete cycles of electrical activity for each cycle of mechanical activity might, they reasoned, suppress ectopic beats and control tachycardias. This line of investigation was pursued by Katz and his co-workers and by Chardack and his co-workers, and later by Braunwald and his co-workers. It was also pointed out by Hoffman, Cranefield, and their co-workers that this form of artificially induced arrhythmia would of necessity induce the enhancement of force of contraction known as postextrasystolic potentiation, and they showed that such maintained postextrasystolic potentiation can reverse all of the features of acute heart failure in dogs. From the Department of Pharmacology, Received for publication May 7, 1965. *Address: Department of Pharmacology. St., New York. N. Y.. 10032.
143
of the heart
College College
During the past 18 months extensive investigations of many aspects of this phenomenon have been carried out on animals and on patients. A conference was held on the subject in January, 1965, and the 22 papers delivered have appeared in the May and June, 1965, issues of the Bulletin of the New York Academy of Medicine. It is possible, therefore, to offer a summary of the present status of this method. Technically, it is fairly simple to induce the desired alteration in cardiac rhythm. Any of the types of electrodes used for ordinary electrical pacemaking of the heart may be employed. Special stimulators for delivering pairs of stimuli have been made available commercially, and with suitable precautions various standard physiologic stimulators may be used. There are many precautions which must be observed with respect to isolation of the stimulators, with respect to juxtaposition of the electrodes to the myocardium, and with respect to the strength and duration of the stimulus. These precautions are discussed at length in the of Physicians of Physicians
and and
Surgeons, Surgeons,
Columbia Columbia
University, University.
New
York,
N. Y.
630
West
168th
proceedings of the conference referred to above. Several cases are no\\’ known in \\,hich the use of paired-pulse stimulations has successfully controlled tachycardias which had proved to be resistant both to drug therapy and to countershock. In one such case a ventricular tachycardia with it downhill course was controlled (the electrical rate remaining high, but the effective mechanical rate being half that of the electrical rate). In that case, pairedpulse stimulation \vas discontinued after 2 days and the tachycardia had subsided. In another case, paired-pulse stimulation n:as employed for 30 days to reduce the effective mechanical rate in a seriously ill patient \\-ho eventually died. In spite of the eventual death of the patient, pairedpulse stimulation was the only means tvhich succeeded in slowing an extremely ominous Life-threatening tachycardia. tachycardias lt:hich are wholly resistant to drug therapy and countershock are as suitable rare but may- be regarded for treatment by paired-pulse stimulation, provided that it is used with the requisite skill and understanding. Paired-pulse stimulation, by producing maintained postextrasystolic potentiation, can greatly enhance the force of contraction of the ventricular myocardium in states of acute cardiac failure. Severe acute heart failure caused (in animals) by outflow constriction, by beta-adrenergic blockade, or by difficult and delayed deimproved by fibrillation is decisively paired-pulse stitnulation during a period in nhich death from cardiac failure \vould otherwise have ensued. Such animals returned to normal cardiac function after cessation of paired-pulse stimulation in experiments in which the cause of the acute heart failure was removed. Clinical experience with the inotropic effects of paired-pulse stimulators is far more limited at present. In a single case, paired-pulse stimulation has been applied continuously for 13 days in a patient with chronic heart failure, in an effort to bring the patient to a level of function sufficient to permit replacement of a valve. The objective signs of improvement in this case bvere slender and the patient did not improve enough to permit operation. The
patient did show nwked subjective 1111. provement and there \vere no serious WII~-plications secondar!. to the use of tht technique. Zo other c;~cs in \\ hich t hc technique WE employed to relieve heart failure have Ixxn reported Among the problems and hazards associated with this inethod are the danger of evoking arrhythmias (in particular ventricular librillation) and the problerti of M:hether the technique causes an increase in the oxygen demands of the myocardium. It R’X clear that the technique can bc used in both animals :ind human beings \\ithout evoking dangerous arrhythmias: it is also clear that faull?~ use of the technique or its use in certain not y.et full!. defined clinical states rl~a!r result in such arrhythmias. No agreement has beeri reached on the problem of the effect of paired-pulse stimulation on the oxygen demands of the myocardium. (-ertain evidence suggests that there is a significant increase. Other evidence sugg-ests that a concomitant increase in coronary arter!. flow Maya compensate for any increased needs for oxygen. It has also been suggested that the increased eilicienc!, of contraction ma!’ actually lessen the needs for oxygen. It is universally agreed that the technique and the wide variety of effects which it produces in the heart raise a host of questions of great importance to cardiac physiology and clinical cardiology. These questions are under investigation in man)’ clinics and laboratories. It is also agreed that the enhancement of the force of contraction and the antiarrhythmic effect of paired-pulse stimulation deserve careful but cautious clinical investigation. It is thought that the technique should be used, at present, only by persons familiar with the underlying physiologic principles, preferably chiefly b\. persons who have thoroughly familiarized themselves \vith its effects by studying it on animals, and chiefIy in clinical situations of an unquestionably life-threatening nature that have failed to respond to conventional therapy. The technique is niost emphatically in an investigative state; riian~~ questions its to its safety and value must be nns\cered. Nevertheless, it is possible that it will have genuine clinical value, and it has already
Volume Number
71 2
provoked many important experiments and a re-examination of many aspects of cardiac physiology. REFERENCES 1. Lopez, J. F., Edelist, A., and Katz, L. N.: Slowing of the heart rate by artificial electrical stimulation with pulses of long duration in the dog, Circulation 28:7.59, 1963. 2. Chardack, W. M., Gage, A. A., and Dean, D. C.: Slowing of the heart bv naired nulse pacemaking, Km. J. Cardiol. -lk:314, i964. 3. Scherlag, B. J., Yeh, B. K., and Cranefield P. F.: Effect of continuous postextrasystolic potentiation on the acutely failed dog heart, Physiologist 7:246, 1964. 4. Braunwald, N. S., Gay, W. A., Morrow, A. G. and Braunwald, E.: Sustained, paired elec-
Paired-pulse
stimulation
of heart
145
trical stimuli. Slowing of the ventricular rate and augmentation of contractile force, Am. J. Cardiol. 14:385, 1964. Cranefield, P. F., Scherlag, B. J., Yeh, B. K., and Hoffman, B. F.: Treatment of acute heart failure by maintained postextrasystolic potentiation, Bull. New York Acad. Med. 40:903, 1964. Lopez, J. F., Edelist, A., and Katz, L. N.: Reducing heart rate of the dog by electrical stimulation, Circulation Res. 15:414, 1964. Braunwald, E., Ross, J., Frommer, P. L., Sonnenblick, E. H., and Gault, J. H.: Clinical observations of paired electrical stimulation of the heart, Am. J. Med. 37:700,1964. Cranefield, P. F., editor: Conference on paired pulse stimulation and postextrasystolic potentiation in the heart, Bull. New York Acad. Med. 41:417, 1965.