Paired or Coupled Cardiac Pacing

Experimental Studies in the Control of Arrhythmias

Constantine J. Tatooles, M.D., Lawrence I. Bonchek, M.D., and Nina S. Braunwald, M.D.

e application of exogenous electrical stimuli to the heart is of increasing importance to the surgeon in the management of T patients with cardiac arrhythmias. The conversion of atrial or

ventricular fibrillation by electrical countershock and the management of complete heart block by sustained electrical pacing have become routine procedures. In addition, a number of investigators have recently demonstrated that, under certain circumstances, the rate of ventricu- lar contraction may be slowed by appropriately timed electrical stimuli applied to the heart [3, 7, 81. This procedure is effective because electri- cal stimulation of the heart in the interval between the QRS complex and the T wave of the electrocardiogram (the relative refractory period) evokes a propagated ventricular depolarization without an accom- panying effective mechanical contraction. This depolarization effectively doubles the interval in which the ventricle is unresponsive to further electrical stimuli and thus lowers the rate of mechanical contraction.

These electrical stimuli can be applied in pairs at a predetermined rate, or they can be coupled to the intrinsic R wave of myocardial depolarization. In coupled pacing, the R wave of a spontaneously oc- curring ventricular depolarization triggers the stimulus which invokes the artificial electrical extrasystole. With paired pacing, spontaneous depolarizations are not permitted, and both the mechanically effective and ineffective depolarizations are induced.

The experimental observation of this physiological phenomenon aroused interest in its application to the control of a variety of ventricu- lar arrhythmias. In this study, the usefulness of coupled and paired pacing in the control of unifocal and multifocal ventricular arrhythmias was assessed in 39 dogs.

From the Clinic of Surgery, National Heart Institute, National Institutes of Health,

Reprint requests should be addressed to Dr. Bonchek. Accepted for publication Jan. 9, 1967.

Bethesda, Md.

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METHODS

Experiments were performed in 39 mongrel dogs of either sex anesthetized with sodium thiopental. The heart was exposed through a transverse sternotomy in the fourth interspaces, and ventilation was maintained with a mechanical respirator supplying air. The pacemaker impulses, electrocardiogram, left ven- tricular and femoral artery pressures, and right ventricular contractile force were simultaneously recorded on a multichannel oscillograph. Pressures were measured with Statham transducers and myocardial contractile force by a Walton-Brodie strain-gauge arch sutured to the right ventricle. Pacemaker impulses were de- livered through wire electrodes sutured to the apical area of the left ventricle. For coupled pacing, the R wave of ventricular depolarization was delivered to the pacing unit by an electrode sutured to the wall of the right ventricle. The circuit was completed by an indifferent electrode sutured to the chest wall. Stimuli were delivered by a battery-powered pulse generator (Medtronic Inc.), which could deliver paired or coupled stimuli at the same rate. Impulses were applied at rates of 80 to 120 per minute with an impulse duration of 3.0 milli- seconds; in all experiments the stimulus amplitude was 3.5 ma.

Regular tachycardia was studied in 5 dogs with spontaneous sinus tachy- cardia, in 8 with regular ventricular tachycardia induced by toxic doses of intravenous ouabain, and in 6 dogs with ventricular tachycardia induced by exogenous stimulation of the ventricles with a separate electrical pacemaker. In 20 dogs irregular ventricular arrhythmias were produced by coronary artery ligation, and in each animal both paired and coupled pacing were applied.

R E S U L T S

Suppression of Regular Arrhythmias. In 5 dogs with spontaneous sinus tachycardia and ventricular rates which averaged 152 per minute, the applica- tion of paired stimuli decreased the rate of ventricular contraction by an average of 43 beats per minute. The underlying sinus tachycardia recurred in all 5 dogs when paired pacing was discontinued. In 8 dogs with regular ventricular tachycardia induced by ouabain overdosage, the average ventricular rate was 189 per minute, and with paired stimulation it was reduced by an average of 58 beats per minute. In 6 dogs in which regular ventricular tachycardia was induced by electrical stimulation at an average rate of 205 per minute, the application of paired stimuli was effective in each instance and lowered the ventricular rate an average of 72 per minute.

Suppression of Irregular Tachycardia. In 20 dogs, ligation of coronary artery branches produced various irregular arrhythmias, including multifocal extra- systoles and ventricular tachycardia. In addition, hypoxia was induced in 11 dogs by hypoventilation. Both modes of pacing were applied in each animal, and in none could a regular rhythm be restored for a significant period of time. In 19 dogs, repeated attempts to control the ventricular rhythm resulted in ventricu- lar fibrillation.

DISCUSSION

Since the preliminary report by Lopez, Edelist, and Katz in 1963 [7], suggesting that the heart rate could be lowered by artificial electri- cal stimulation, numerous investigators have described the effects of sustained paired stimuli on heart rate, contractile force, and myocardial oxygen consumption [1, 3, 5-91. Though it has been amply demon- strated in the laboratory that heart rate may be lowered while myo-

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NO'I'E: Control of Arrhythmias

cardial contractile force is increased, there have been few practical clinical applications of these observations. Braunwald et al. have dis- cussed the factors to be considered before utilizing this technique for the treatment of heart failure and describe disappointing results thus far [2]. It might be hoped, however, that this technique would be suc- cessful in the control of cardiac arrhythmias. The effective control of regular ventricular arrhythmias by paired or coupled pacing in these experiments confirms the findings of other investigators [4]. The con- sistent initiation of ventricular fibrillation when pacing was attempted in hearts with experimental irregular, multifocal arrhythmias, how- ever, indicates the potential hazard of applying this method clinically in similar situations. The possibility that these hearts might ultimately have fibrillated even without the application of external electrical stimuli cannot be considered a satisfactory explanation. Hearts with irregular ventricular tachycardia are constantly in danger of fibrillat- ing, and useful therapeutic interventions should either be rapidly effec- tive, or at least do nothing to hasten the onset of fibrillation. In these studies, when fibrillation occurred, it coincided with the initiation of pacing and was often irreversible.

Paired us. Coupled Pacing in the Control of Arrhythmias. In coupled pacing, the intrinsic pattern of electrical activity of the heart is not altered, but the refractory period is prolonged by induced elec- trical extrasystoles, which slow the rate of mechanical contraction. It might be anticipated, therefore, that coupled pacing would be ineffec- tive in controlling an irregular arrhythmia, since the disordered pattern persists. Paired pacing, however, not only prolongs the refractory period with the second stimulus of each pair, but attempts to impose on the heart a new rhythm triggered by the first stimulus of each pair. Nonetheless, paired pacing was no more effective than coupled pacing, as it induced fibrillation in a comparable number of hearts. Analysis of the results of our experiments with paired pacing suggests that repeated attempts to suppress an irregular arrhythmia with paired pacing (a method which is, by definition, nonsynchronous with the heart's in- trinsic rhythm) will ultimately result in the application of a stimulus during a portion of the cardiac cycle when the heart is particularly vulnerable to fibrillation.

These experimental studies indicate that paired or coupled pacing are effective in slowing regular tachycardias which originate from a single ventricular or supraventricular focus. They are of no benefit, and even hazardous, in the control of irregular and multifocal experi- mental ventricular arrhythmias that result from myocardial ischemia. Ventricular arrhythmias that occur clinically have a variety of causes, and the application of paired or coupled pacing may have a different result; extreme caution in their use is clearly indicated, however.

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SUMMARY

The effectiveness of paired and coupled pacing in the control of regular and irregular arrhythmias was assessed in 39 dogs.

In 6 dogs with spontaneous sinus tachycardia, 8 with regular ven- tricular tachycardia induced by digitalis intoxication, and 6 with regu- lar ventricular tachycardia produced by exogenous stimulation of the ventricles, paired or coupled pacing effectively slowed the ventricular rate. In 20 dogs, attempts to control irregular, multifocal ventricular arrhythmias induced by coronary artery ligation consistently resulted in ventricular fibrillation.

The study indicates that paired or coupled pacing is of no benefit, and even hazardous, when utilized to control irregular or multifocal ventricular arrhythmias.

REFERENCES

1. Braunwald, N. S., Gay, W. A., Jr., Morrow, A. G., and Braunwald, E. Slow- ing of the ventricular rate and augmentation of contractile force by sustained paired electrical stimuli. Amer. J. Cardiol. 14:385, 1964.

2. Braunwald, E., Ross, J., Sonnenblick, E. H., Frommer, P. L., Braunwald, N. S., and Morrow, A. G. Slowing of the heart rate, electroaugmentation of ventricular performance, and increase of myocardial oxygen consumption produced by paired electrical stimulation. Bull. N.Y. Acad. Med. 41:481, 1965.

3. Chardack, W. M., Gage, A. A., and Dean, D. C. Slowing of the heart rate by paired pulse pacemaking. Amer. J . Cardiol. 14:374, 1964.

4. Frommer, P. L., Robinson, B. F., and Braunwald, E. Studies on digitalis: XII. The effects of paired electrical stimulation on digitalis-induced arrhyth- mias. J. Pharmacol. Exper. Ther. 151:1, 1966.

5. Hoffman, B. F., Bindler, E., and Suckling, E. E. Postextrasystolic potentia- tion of contraction in cardiac muscle. Amer. J. Physiol. 185:95, 1956.

.6. Klocke, F. J., Braunwald, E., and Ross, J. Oxygen cost of electrical activa- tion of the heart. Circ. Res. 18:357, 1966.

7. 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 28~779, 1963.

8. Lopez, J. F., Edelist, A., and Katz, L. N. Reducing heart rate of the dog by electrical stimulation. Circ, Res. 15:414, 1964.

9. Ross, J., Sonnenblick, E. H., Kaiser, G. A., Frommer, P. L., and Braunwald, E. Electroaugmentation of ventricular performance and oxygen consumption by repetitive application of paired electrical stimuli. Circ. Res. 4:332, 1965.

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