Postgrad Med J: first published as 10.1136/pgmj.50.585.447 on 1 July 1974. Downloaded from

Postgraduate Medical Journal (July 1974) 50, 447-453.

Verapamil in the treatment of paroxysmal supraventricular DENNIS M. KRIKLER ROWORTH A. J. SPURRELL M.D., F.R.C.P., F.A.C.C. B.Sc., M.B., M.R.C.P. Cardiovascular Division, Royal Postgraduate Department of Cardiology, Medical School, London, W.12 Guy's Hospital, London, S.E.1

Summary nized that its antiarrhythmic activity and any action Verapamil is a novel antiarrhythmic agent which improving cardiac ischaemia is determined by its appears to act as a calcium-ion antagonist, blocking ability to prevent calcium inflow across the cell calcium transport across the myocardial cell mem- membrane (Nayler et al., 1968; Fleckenstein, Doring brane. It was given intravenously, in a dose of 10 mg, and Kammermeier, 1968; Nayler and Szeto, 1972; to thirty-two patients suffering from paroxysmal Singh and Vaughan Williams, 1972). In clinical use supraventricular tachycardia, and was its antiarrhythmic properties have been demon- achieved promptly in all. Identical results were ob- strated by Bender et al. (1966) and, in anaesthetized tained in a further ten patients with supraventricular subjects, by Brichard and Zimmerman (1970). associated with the Wolff-Parkinson- Given intravenously, it has been shown to have a White or other pre-excitation syndromes. In a separate potent effect in slowing and regularizing the ventri- group of eighteen patients in whom A-V junctional cular response in atrial (Schamroth, tachycardias were induced during intracardiac electro- 1971; Schamroth, Krikler and Garrett, 1972). by copyright. graphy, conversion to sinus rhythm was achieved in In the study reported by Schamroth et al. (1972) fifteen patients, with prolongation of the cycle length twenty patients with paroxysmal supraventricular in the others. Circus-movement tachycardias were in- tachycardia all responded promptly to intravenous duced in eight patients with the Wolff-Parkinson- verapamil. We have now extended the number of White syndrome, and conversion to sinus rhythm was cases treated, and have included a further group in achieved in seven. The results were less consistent in whom paroxysmal supraventricular tachycardias patients with other supraventricular in- were induced during intracardiac electrographic cluding ectopic and , studies. The response in some other arrhythmias is and, in the single patient with supraventricular and also briefly considered. http://pmj.bmj.com/ , only the former was con- trolled. In the single patient with Methods complicating the Wolff-Parkinson-White syndrome Verapamil was administered intravenously as who received verapamil, sinus rhythm was restored. previously described (Schamroth et al., 1972). A Side effects were few and mild, with rare exceptions of dose of 10 mg was given over a period of 15-30 sec. profound hypotension, and ; their In all cases the patients were in the recumbent posi- is and reasons are advanced a 12-lead was first recorded, management discussed, tion, electrocardiogram on September 28, 2021 by guest. Protected why their occurrence is likely to be related either to the and the was identified. A continuous concomitant administration ofbeta-adrenergic blockers electrocardiographic recording was started before or to the presence of sinoatrial disease. It appears that the injection and continued until sinus rhythm had verapamil is particularly saitable for the treatment of been restored, or for at least 5 min. The blood pres- supraventricular tachycardias due to a circus move- sure was recorded before, immediately after and on ment as calcium antagonism is likely to be most effec- several occasions subsequent to the administration tive in the N region of the . of the verapamil. In the patients studied in the laboratory, intra- VERAPAMIL was originally considered to be a coro- cardiac electrographic recordings were made and nary vasodilator (Haas and Hairtfelder, 1962), and stimulation carried out as previously described on this basis was introduced for the treatment of (Spurrell, Krikler and Sowton, 1973). Catheters were cardiac ischaemia (Tschirdewahn and Klepzig, 1963; passed from the femoral veins and positioned in the Hoffmann, 1964). Under experimental conditions, right atrium, the right ventricle, and across the tri- potent antiarrhythmic activity was noted (Melville, cuspid valve in apposition to the ; in Shister and Huq, 1964; Schmid and Hanna, 1967; some patients, transseptal puncture was performed Kaumann and Aramendia, 1968) and it is now recog- and recordings made from the left atrium. In all Postgrad Med J: first published as 10.1136/pgmj.50.585.447 on 1 July 1974. Downloaded from

448 D. M. Krikler and R. A. J. Spurrell

Vi , I i i TTIi :l,-- III l,I [/]z 1I [ 1' [ i iA" , [ i i

- It-

FIG. 1. ECG, showing paroxysmal supraventricular tachycardia at 160 beats a minute, with abrupt conversion to sinus rhythm (100 beats a minute) 40 sec after injection of verapamil. V2

- I 'Li I I- I I I I I

i I I l lail Al! r .1 I I 1,AILL1 . - - J', l- - J Jarrltr

. --- -Ir------· I l I L! J lJI A I .- .--- II

FIG. 2. ECG, showing paroxysmal supraventricular tachycardia with conversion to sinus rhythm 30 sec after verapamil, with ventricular extrasystole at transition. by copyright.

T 'l I SSS 244;;n ;TXii;BEii---$-

11f1 24 II TTT r r Trrnl .... E.w14tfl1ml-tX11 .....-9-

48 http://pmj.bmj.com/ 1161 alRl I EM A II *I TT 1 1IVT 1 lTSITIXt1I 60 H E t 77 7 11i, . . . . .I I .IL I IIL I I . - ..1 1 1111 I I-IIIIs

FIG. 3. ECG (lead II) showing paroxysmal supraventricular tachycardia (160 beats a minute) in upper panel (0 = prior to injection of verapamil). The middle two panels start 24 and 48 sec after verapamil, respectively, and show persis- PR tence of tachycardia pattern with progressive slowing of heart rate down to 84 beats a minute. Note the progressive on September 28, 2021 by guest. Protected lengthening to 0-48 sec. In the bottom panel (60 sec) sinus rhythm has been restored at a rate of 78 beats a minute, with a normal PR interval of 0-16 sec. patients the procedure was essential to obtain infor- responded promptly to the verapamil. Typical re- mation in the interests of their health; they were fully sponses are shown in Figs. 1 and 2, and consisted informed of what was to be done, and consented to either of an abrupt change to sinus rhythm, or one the study. Verapamil was administered in the same punctuated by the occurrence of one or more ventri- dose and tracings recorded as appropriate both from cular extrasystoles; there was often a brief period of intracardiac electrodes and surface leads, and the , lasting for 30-60 sec. There was response to verapamil noted. occasional evidence of antero-grade A-V nodal con- duction delay prior to restoration of sinus rhythm, Results as is demonstrated in Fig. 3, where progressive PR Clinical cases lengthening occurred with persistence of the tachy- Thirty-two patients suffered from paroxysmal cardia, until abrupt restoration of sinus rhythm with supraventricular tachycardia due to a circus move- a normal PR interval. ment affecting the atrioventricular node, and all Mild transient hypotension, with a drop in the Postgrad Med J: first published as 10.1136/pgmj.50.585.447 on 1 July 1974. Downloaded from

Verapamil and tachycardia 449

, =, 'I- - i. IT ' |' T i .. .:... .1. .1. IT

I. 77

VI

FIG. 4. ECG, showing paroxysmal supraventricular tachycardia (rate 200 beats a minute with alternating intranodal by copyright. conduction pathways or dissipation of intraventricular conduction disturbance affecting every third beat), with runs of broad complexes due to paroxysmal ventricular tachycardia at 135 beats a minute. Note fusion beats (X) at interface of dual tachycardias. VI 35

ni .It1

ITTrm-1

L .1 lrrIl-t. http://pmj.bmj.com/

FIG. 5. ECG, lead VI: 35 sec after verapamil, paroxysmal supraventricular tachycardia is completely suppressed, un- masking ventricular tachycardia which persisted until DC cardioversion used. systolic pressure to 80-100 mmHg for 2-3 min, was This is similar to our further experience with atrial noted in four patients, but recovery was sponta- flutter, which has proved less promising than the neous. However, in a further three patients, more original findings (Schamroth et al., 1972). We have marked hypotension, of the order of 60-40 mmHg, administered verapamil to twenty patients, achieving on September 28, 2021 by guest. Protected was noted, and all these patients were then found to sinus rhythm in five and a transient increase in the have received oral beta-blocking agents (propranolol degree of in the remaining or practolol) in normal therapeutic doses on the same fifteen, without altering the cycle length of the flutter day. waves in any. Four patients with ectopic atrial tachycardia A 61-year-old man who suffered from a dual received verapamil. In one patient, there was con- of both supraventricular version to sinus rhythm, preceded by A-V nodal and ventricular origin (Fig. 4), possibly due to Wenckebach periods (see Fig. 7 in the report by digitalis intoxication, responded promptly to intra- Schamroth et al., 1972). In another patient, in whom venous verapamil in that the supraventricular tachy- the aetiology was congestive , the cardia was completely controlled, but the ventricular tachycardia was converted to atrial fibrillation which tachycardia persisted (Fig. 5), with consequent spontaneously changed to sinus rhythm 1 day later; haemodynamic deterioration and the need for DC in the other patients, in whom the arrhythmia was shock. believed to be due to thyroxine overdose in one and Ten patients who had reciprocating tachycardias to cardiac ischaemia in the other, there was a tran- associated with pre-excitation syndromes all re- sient increase in the degree of atrioventricular block. sponded promptly to intravenous verapamil, with Postgrad Med J: first published as 10.1136/pgmj.50.585.447 on 1 July 1974. Downloaded from

450 D. M. Krikler and R. A. J. Splrrell

I'[ L ]I'JI T 1rlIq ]I[ iI t ~IIIIt1 I] I'Ti t r IrLm ]rT 71 E L II i II

4 IJff[~ii1 !.. 1il [t i! illlU !i iIl tI I1I I Il II l .II lJr l Ilfl l I III i]L]I IIILI Iii' 1

...... r J lJII I J]IIIIIIIl]ll[]TI'lJ!.J [;J .m JJI] J ...... 10[II J 1[IItIJ[I jjll ...... l 6

10

FIG. 6. ECGs, lead II, showing response of patient with atrial fibrillation com- plicating Wolff-Parkinson-White syndrome. 0 - control tracing, with maximal pre-excitation pattern and ventricular response of 230 beats a minute. Four minutes after verapamil, the same pattern persists but the ventricular rate has fallen to 140. At 6 min, junctional rhythm with retrograde P'-waves, at 80 beats a minute; at 10 min, restoration of sinus rhythm with Wolff-Parkinson-White appearances (note negative delta wave), at 72 beats a minute. by copyright.

1 C--, I r l I I Ii [ I I I I II II Il I I Ill ;II§i~l]W11\t1-::-t-illi'I T -l ltlmlililt-I I [Al I I I11lIJ-IIJILLl[ IJ U-IAl I I][ I L &EjwIL1 I I ILLdb.j..ll IJ~[ I ~ III]1-- I II

I I 111 oVR aVL oVF

VI V2 V3 V4 V5 V6 http://pmj.bmj.com/

T L i!iiii Iii»i iJ I IIrII III T:III'I IIII-II ll'I:l II IIIIIIl 1 1 ^ ':,l: I I-ln--lr-'f11

ii I * I II I II I i I ][ i I l Il Il][l lllllllll

I I I I I I I .T .... Ii I I I* I I tl [ I I I I I Ill iT'I I I..... II 'T., -lIlliIIIIItIII1I i11I I It [!I~ T4II1-1IT] [ II i IIIIII~!!11 FiIII~t.l llll~ ! I* I I ~

11 7 |~~~ ~ 111 1111|IIII|Ir-lI IrII*III1 1'1 T 1 1 11l1]1|IIIIsI1-11 11 rrlll21 [1 1 ti l l11ll ...... I ...I II Iii1111111IIIII 1 1!trlr|1TII |x|+||[ wi A ||tEt|| i * Ii*- I 111111 S1- LX|-|E^B|Illllli!1 1-lI TTAT ILI ll I 1 I*IIIIn a I.lllllTNI I *I TI I- nil [I 1J~]ILTT-Ii IlIlZ nll*1l[liI ' l TI Il; [ 1 [ ITITITrTr1[llJJlI II II I I I ...... 1 T §i1 s BfB - - I - ,U ~Trl Fl on September 28, 2021 by guest. Protected r gIwIUIIlllllrIIIrT.111*IIilllllllIlI Lllll lKiB l I [ l llll[.-{:I:: I:: L : T...... IL[I Il ~III ItJ I[

FIG. 7. Wolff-Parkinson-White syndrome, Type B, with negative delta wave and dominant S in VI. conversion to sinus rhythm within 2 min. One of ventricular pacing before sinus rhythm was restored. these patients, a 68-year-old woman, appears also to An additional observation, in a single case of have sinoatrial disease as judged by marked sinus atrial fibrillation complicating the Wolff-Parkinson- bradycardia and sinus arrhythmia and junctional or White syndrome, is instructive. A 36-year-old woman ventricular escape beats while not receiving anti- had suffered one previous attack of palpitations, and arrhythmic medications; paroxysmal supraventri- was admitted with an irregular tachycardia with cular tachycardia occurred despite the prophylactic wide QRS complexes (Fig. 6). This has the appear- oral administration of practolol 400 mg daily. She ance of atrial fibrillation complicating the Wolff- received 10 mg verapamil intravenously, which pro- Parkinson-White syndrome, most of the impulses duced prompt control of the arrhythmia, but with being conducted totally down the anomalous tract. temporary sinus arrest, necessitating temporary The response to intravenous verapamil was at first Postgrad Med J: first published as 10.1136/pgmj.50.585.447 on 1 July 1974. Downloaded from

Verapainil and tachycardia 451 slowing of the ventricular response (4 min), then development of junctional rhythm with narrow QRS complexes (6 min), and, after 10 min, restora- HAE X |4 tion of sinus rhythm with the pre-excitation pattern (see also Fig. 7). A' LAE ^/ Intracardiac studies Eighteen patients with A-V junctional tachy- cardias were given verapamil while in circus-move- ment tachycardia, and in fifteen patients the tachy- AHV cardia was terminated within 2-3 min. In the remain- HBE7r- r a ing three cases, the cycle length was prolonged in both the anterograde and retrograde directions but reciprocation continued. Cessation of tachycardia ECG ---. = could take place with interruption of the circuit either in the anterograde pathway (Fig. 8) or in the retro- Atrium 390 360 545 grade pathway (Fig. 9) within the atrioventricular AV node. Of these fifteen patients-in whom there was Ventricle 360 390 360 545 no reason to suspect pre-excitation-the presence of A-H 80 A-H 85 H-A' 375 P-A 29 H-A 310 H-A 275 A-H 72 a concealed bypass outside the atrioventricular node H-V 52 was suggested in five by constant ventriculoatrial H-V 45 H-V 46 conduction times which were not influenced by FIG. 9. Intracardiac electrogram, conventions as in Fig. verapamil (Spurrell, Krikler and Sowton, 1974a). 8. Tachycardia stops after fourth V wave, i.e. in retro- with Wolff-Parkinson-White grade conduction within A-V node; the next two com- Eight patients syn- are sinus beats with normal atrioventricular drome were given verapamil while in circus-move- plexes by copyright. ment tachycardia during laboratory studies, and in conduction. seven of these patients the tachycardia was termi- nated within 2 min. In the remaining patient, a suitably-timed extrasystole was injected in order to disrupt the circuit, as described by Wellens (1971). Comment Whether circus-movement tachycardia is due to

A' a process involving the atrioventricular node alone, http://pmj.bmj.com/ LAE-L------A^ -- --- Y-- or whether the circuit involves an anomalous path- way as well as the A-V node, verapamil appears to be a highly effective antiarrhythmic agent, acting AH V directly on the A-V node. The onset of action is rapid, and the response prompt. Intracardiac studies show that verapamil has a potent effect in prolonging A-V nodal conduction (Puech, 1972a; Husaini et al., 1973; Roy, Spurrell and Sowton, 1974). However, on September 28, 2021 by guest. Protected ECG -" .... in a certain number of cases, side effects have been noted, including hypotension, bradycardia and on rare occasions, (Benaim, 1972; Booth- by, Garrard and Pickering, 1972; Sacks and Ken- AV.- nelly, 1972). In the majority of such cases, the prior administration of beta-adrenergic blockers appears Ventricle 495 495 H-A' 45 Rate 122/min P-A 45 to have been an important factor. As has been shown A'-H 450 A-H 60 and Szeto and beta- H-V 45 HHV 50 by Nayler (1972), verapamil H-V adrenergic blockers both have calcium-antagonistic FiG. 8. Intracardiac electrogram showing high right properties on the cell though working in totally atrial electrogram (HAE), low right atrial electrogram different ways. Whereas verapamil blocks transport (LAE), His bundle electrogram and simultaneous surface of calcium across the cell membrane, beta-blockers ECG lead. Arrhythmias stopped after third A' wave, i.e. interfere with intracellular calcium in anterograde direction within A-V node. The fourth handling. Separ- complex shows a sinus beat with normal atrioventricular ately each has a mild negative inotropic effect; when conduction. given together, this is additive (Nayler, 1974). Postgrad Med J: first published as 10.1136/pgmj.50.585.447 on 1 July 1974. Downloaded from

452 D. M. Krikler and R. A. J. Spurrell Another possible mode of adverse reaction to Wolff-Parkinson-White syndrome (Fig. 8) was posi- verapamil implies depression of S-A nodal activity. tive but difficult to understand unless it can be in- Under normal circumstances, the administration of ferred that the initial decrease in ventricular rate was verapamil has very little if any effect on S-A nodal due to a blocking action at the atrio-bypass junction automaticity (Puech, 1972a; Roy et al., 1974), but and a subsequent antifibrillatory effect on the atrium, if there is sinoatrial disease, it is to be anticipated restoring sinus rhythm via a phase of junctional that any slight inherent tendency to depression will rhythm. Verapamil does not lengthen the refractory be increased. For this reason verapamil should be period of the bypass, tending not to influence it or used with caution in patients with the 'sick sinus to produce slight shortening (Spurrell et al., 1974b). syndrome' who present with supraventricular tachy- In the vast majority of published reports, results cardia (Husaini et al., 1973), as, indeed, should other of treatment have been excellent (Abaza et al., 1972; drugs. The summation of these effects is well shown Gotsman et al., 1972; Filias and Zanoni, 1972; in the patient with Wolff-Parkinson-White syndrome Puech, 1972b). Verapamil has been shown to have and sinoatrial disease in whom transient cardiac an important place in the treatment of paroxysmal standstill was produced after correction of her circus- A-V nodal tachycardia. Our experience has been con- movement tachycardia. fined to its intravenous use and we have not made We have encountered seven other patients in any systematic assessment of its efficacy when given whom there were adverse effects after intravenous by mouth for treatment or prophylaxis, though verapamil. In four, verapamil had been administered others have reported satisfactory results (Bender. to patients who were already receiving beta-blockers. 1970; Abaza et al., 1972; Filias and Zanoni, 1972; A 64-year-old patient with the Wolff-Parkinson- Puech, 1972b). Its preferential action on the A-V White syndrome who had received repeated intra- node may be due to the fact that its potent calcium venous injections of practolol and propranolol and antagonism is most sensitively felt in the N region of who had needed DC cardioversions and triple-beat the node, where a slow Na+-Ca++ channel deter- ventricular pacing, suffered from repeated bouts of mines conduction (Zipes, 1973). Provided precau-by copyright. tachycardia with rates up to 300 a minute, and epi- tions are taken in the selection of patients and in the sodes of , for 4 days: verapamil exclusion of those who have recently received beta- produced conversion to sinus rhythm but she col- adrenergic blockers, use of verapamil in supraventri- lapsed with asystole. cular tachycardias provides an important and useful While Puech (1972a) has found atropine regularly form of therapy. Whether the mechanism involves to reverse the effect of verapamil on the A-V node, the A-V node alone or the A-V node plus an extra- others have found the response to be incomplete nodal bypass, verapamil has been shown to be a (Roy et al., 1974). Atropine 1 mg intravenously safe and effective primary agent for the treatment of should, however, be given if a reaction occurs, circus-movement supraventricular tachycardias. http://pmj.bmj.com/ followed by intravenous calcium (10-20 ml of 10% solution); an intravenous infusion of isoprenaline References may be needed and, rarely, temporary ventricular ABAZA, A., BODINIER, C., AZIZA, CL. & GARNIER, J.C. (1972) pacing. The chance of an adverse reaction can be Etude clinique d'un nouvel antiarythmique. Coeur et Mede- minimized if it can be ensured that the has cine Interne, 11, 757. patient BENAIM, M.E. (1972) Asystole after verapamil. British not been receiving a beta-blocker for at least 6 hr Medical Journal, 2, 169. prior to the administration of verapamil. Suspicion BENDER, F. (1970) Die Behandlung der tachycarden Arrhyth- of sinoatrial disease merits especial caution in the mien und der arteriellen Hypertonie mit Verapamil. on September 28, 2021 by guest. Protected use of must be Arzneimittel-Forschung, 20, 1310. verapamil. However, perspective BENDER, F., KOJIMA, N., REPLOH, H.D. & OELMANN, G. maintained, as adverse reactions occur to other anti- (1966) Behandlung von Rhythmusstorungen des Herzens arrhythmic agents, e.g. beta-adrenergic blockers durch Beta-Rezeptorenblockade des Atrioventrikular- (Szekely, 1972), and G. C. Sutton (personal commu- gewebes. Medizinische Welt, 17, 1120. has observed and BRICHARD, G. & ZIMMERMANN, P.E. (1970) Verapamil in nication) hypotension pulmonary cardiac dysrhythmias during anaesthesia. British Journal oedema in a patient with paroxysmal supraventricu- of Anaesthesia, 42, 1005. lar tachycardia treated with intravenous practolol BOOTHBY, C.B., GARRARD, C.S. & PICKERING, D. (1972) who failed to return to sinus rhythm. Furthermore, Intravenous verapamil in cardiac arrhythmias. British ill who have suffered from for Medical Journal, 2, 349. patients arrhythmias FILIAS, N. & ZANONI, G. (1972) Klinische Analyse der anti- a protracted period are likely to have catecholamine arrhythmischen Wirkung des Verapamils. Schweizerischer depletion, and may well react adversely both to beta- Medizinische Wochenschrift, 102, 406. adrenergic blockers and to verapamil, or indeed any FLECKENSTEIN, A., DORING, H.J. & KAMMERMEIER, H. (1968) substance that decreases the amount of calcium Einfluss von Beta-Receptorenblockern und verwandten Substanzen auf Erregung, Kontraktion und Energiestoff- entering or available within the myocardial cell. wechsel der Myokardfaser. Klinische Wochenschrift, 46, The response in atrial fibrillation complicating the 343. Postgrad Med J: first published as 10.1136/pgmj.50.585.447 on 1 July 1974. Downloaded from

Verapamil and tachycardia 453 GOTSMAN, M.S., LEWIS, B.S., BAKST, A. & MITHA, A.S. SCHAMROTH, L. (1971) Immediate effects of intravenous ver- (1972) Verapamil in life-threatening tachyarrhythmias. apamil on atrial fibrillation. Cardiovascular Research, 5, South African Medical Journal, 46, 2017. 419. HAAS, H. & HARTFELDER, G. (1962) a-lsopropyl-a-[(N- SCHAMROTH, L., KRIKLER, D.M. & GARRETT, C. (1972) methyl - N - homoveratryl) - y - amino - propyl] - 3,4 - di- Immediate effects of intravenous verapamil in cardiac methoxyphenylacetonitril, eine Substanz mit koronarge- arrhythmias. British Medical Journal, 1, 660. fasserweiternden Eigenschaften. Arzneimittel-Forschung, SCHMID, J.R. & HANNA, C. (1967) A comparison of the anti- 12, 549. arrhythmic actions of two new synthetic compounds, HOFFMANN, P. (1964) Behandlung koronarer Durchblutungs- iproveratril and MJ 1999, with quinidine and pronethalol. storungen mit Isoptin in der Praxis. Medizinische Klinik, Journal of Parmacology and Experimental Therapeutics, 59, 1387. 156, 331. HUSAINI, M.H., KVASNICKA, J., RYDEN, L. & HOLMBERG, S. SINGH, B.N. & VAUGHAN WILLIAMS, E.M. (1972) A fourth (1973) Action of verapamil in sinus node, atrioventricular, class of anti-dysrhythmic action? Effect of verapamil on and intraventricular conduction. British Heart Journal, ouabain toxicity, on atrial and ventricular intracellular 35, 734. potentials, and on other features of cardiac function. KAUMANN, A.J. & ARAMENDIA, P. (1968) Prevention of ven- Cardiovascular Research, 6, 109. tricular fibrillation induced by coronary ligation. Journal SPURRELL, R.A.J., KRIKLER, D.M. & SOWTON, E. (1973) of Pharmacology and Experimental Therapeutics, 164, Two or more intra AV nodal pathways in association with 326. either a James or Kent extranodal bypass in 3 patients MELVILLE, K.I., SHISTER, H.E. & HUQ, S. (1964) Iproveratril: with paroxysmal supraventricular tachycardia. British Experimental data on coronary dilation and antiarrhyth- Heart Journal, 35, 113. mic action. Canadian Medical Association Journal, 90, 761. SPURRELL, R.A.J., KRIKLER, D.M. & SOWTON, E. (1974a) NAYLER, W.G. (1974) The sub-cellular regulation of myo- Concealed bypass of the AV node in patients with paroxys- cardial function. American Heart Journal. (In press.) mal supraventricular tachycardia revealed by intracardiac NAYLER, W.G., MCINNES, I., SWANN, J.B., PRICE, J.M., electrical stimulation and intravenous verapamil. American CARSON, V., RACE, D. & LOWE, T.E. (1968) Some effects Journal of Cardiology (in press). of iproveratril (isoptin) on the cardiovascular system. SPURRELL, R.A.J., KRIKLER, D.M. & SOWTON, E. (1974b) Journal of Pharmacology and Experimental Therapeutics, The effects of verapamil on the electrophysiological proper- 161, 247. ties of the anomalous atrioventricular connexions in NAYLER, W.G. & SZETO, J. (1972) Effect of verapamil on Wolff-Parkinson-White syndrome. British Heart Journal,

contractibility, oxygen utilization, and calcium exchange- 36, 256. by copyright. ability on mammalian heart muscle. Cardiovascular Re- SZEKELY, P. (1972) In: Proceedings of United Kingdozm- search, 6, 120. Scandinavian Cardiology Meeting (Ed. by J. L. Kennedy). PUECH, P. (1972a) Dissection de la Conduction Sinoventricu- Watford, Astra Chemicals Limited. laire pour l'Etude du Verapamil Injectable (circulated TSCHIRDEWAHN, B. & KLEPZIG, H. (1963) Klinische Unter- privately). suchung fiber die Wirkung von Isoptin und Isoptin S bei PUECH, P. (1972b) Experimentation Clinique de l'lsoptine In- Patienten mit Koronarinsuffizienz. Deutsche Medizinische jectable et par Voie Orale dans les Troubles du Rythme Wochenschrift, 88, 1702. Cardiaque (circulated privately). WELLENS, H.J.J. (1971) Electric Stimulation of the Heart in RoY, P.R., SPURRELL, R.A.J. & SOWTON, E. (1974) The effect the Study and Treatment of Tachycardias. (Ed. by H. E. of verapamil on the conduction system in man. Postgraduate Stenfert Kroese, N.V.). Leiden. Medical Journal, 50, 270. ZIPES, D.P. (1973) In: Cardiac Arrhythmias (Ed. by L. S. SACKS, H. & KENNELLY, B.M. (1972) Verapamil in cardiac Dreifus and W. Likoff), p. 55. New York, Grune and http://pmj.bmj.com/ arrhythmias. British Medical Journal, 2, 716. Stratton. on September 28, 2021 by guest. Protected