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Effects Ofnew Beta-Blocking Agent Wolff-Parkinson-White Syndrome

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Effects Ofnew Beta-Blocking Agent Wolff-Parkinson-White Syndrome Br Heart J: first published as 10.1136/hrt.34.12.1272 on 1 December 1972. Downloaded from British Heart Journal, I972, 34) I272-I282. Effects of new beta-blocking agent (DL-tiprenolol) on conduction within normal and anomalous atrioventricular pathways in Wolff-Parkinson-White syndrome J. Roelandt, L. Schamroth, and P. G. Hugenholtz From the Thoraxcentre, University Hospital and Medical Faculty, Rotterdam, The Netherlands; and the Baragwanath Hospital and the University of the Witwatersrand, J7ohannesburg, South Africa The effects of DL-tiprenolol (DU 2I445) - a new beta-receptor blocking agent - and atropine on both normal and abnormal conduction pathways in the Wolff-Parkinson-White (WPW) syn- drome were studied by means of His bundle electrograms and atrial pacing. It was shown that DU 2I445 slows conduction through both pathways significantly (P, o os) and has a potential value in the treatment of symptomatic WPW syndrome and perhaps in other types of re-entrant tachycardias. The effects ofatropine were also studied in 2 patients. Atropine did not affect bypass conduction whereas A V conduction velocity was definitely increased. copyright. The study also shedsfurther light on the mechanism of WPW syndrome. It was found that the bypass had different conducting properties and was most probably a different conducting structure from the normal A V pathway. Surgical division of the anomalous pathway reason for a surgical approach, virtually as a in the Wolff-Parkinson-White (WPW) syn- measure of desperation. http://heart.bmj.com/ drome has recently been carried out with some Little is known about the conduction success in a few patients with incapacitating properties of, and the influence of drugs on, attacks of tachycardia (Cobb et al., I968; the anomalous bypass. Only a few studies have Sealy, Boineau, and Wallace, I970). Attempts dealt with this problem (Roelandt, Draulans, by others have been unsuccessful (Burchell et and Roos, I970; Agha, Myerburg, and Castel- al., I967; Cole et al., I970; Lindsay et al., lanos, I97I; Roelandt et al., I972). Study of I97I) and in general the results of this surgical the pharmacological action of drugs on both procedure have not, until recently, been par- the normal and the anomalous pathways is now on September 24, 2021 by guest. Protected ticularly encouraging. Conventional medical possible through the analysis of His bundle treatment is therefore still the most widely electrograms and atrial pacing. This method of used method of management, and most gener- study may provide objective data for the ally known antiarrhythmic drugs have, at one rational treatment of a symptomatic patient time or another, been proposed for the pre- (Wallace et al., I971). vention and treatment of the arrhythmias This paper reports the evaluation of DL- associated with this syndrome. tiprenolol (DU 21445) - a new beta-receptor The administration of beta-receptor block- blocking agent - on conduction within the ing agents has been shown to be particularly normal and abnormal pathways of the WPW effective in the prevention and treatment of syndrome, by means of His bundle electro- the attacks of paroxysmal reciprocating tachy- grams and atrial pacing. cardias (Gianelly, Grifin, and Harrison, I967; Gibson and Sowton, I969). Neverthe- less, failures with these agents have occurred Methods in some the most of extensively studied series A multipolar electrode catheter was introduced (Dreifus et al., I968; Sealy et al., I970; Lind- percutaneously into the femoral vein under local say et al., I97I); and this has constituted the anaesthesia. The catheter was fluoroscopically Received 9 June 1972. positioned for the recording of His bundle electro- Br Heart J: first published as 10.1136/hrt.34.12.1272 on 1 December 1972. Downloaded from Effects of new beta-blocking agent (DL-tiprenolol) 1273 grams as described by Scherlag et al. (I969). control 'pace-run' was also studied. In Case 4 This bipolar electrogram was derived from two the effect of atropine was studied the day before adjacent electrodes on the catheter and led into the DU 21445 study. the AC input of a four-channel Elema direct- DL-tiprenolol (DU 21445) is a new beta-block- writing electrocardiograph with an appropriate ing agent (Philips-Dulphar N.V. Weesp, The time constant. Standard lead II and lead Vi were Netherlands) with about the same pharmacologi- recorded simultaneously for reference purposes. cal actions as DL-propranolol, but three times Paper speeds of 50 and ioo mm a second were more active in reducing heart rate during exercise used for reproduction and measurement, respec- (Kesteloot et al., I970). tively. Statistical analysis of the data obtained with All intervals are expressed in milliseconds DU 21445 was executed on an IBM 360 computer. (msec) with an accuracy of ± 5 msec. The values of the intervals at the pacing rates In addition, a bipolar electrode catheter was used for statistical analysis were derived from the introduced percutaneously and positioned against basic data by linear interpolation on the scale of the lateral wall of the right atrium in the region paced heart rates. The statistical test used was of the sinus node for artificial atrial pacing by Wilcoxon's signed rank test for paired differences. means of a suitable variable pacemaker. Great care was taken to ensure proper grounding of all Subjects equipment. The right atrium was usually paced There were 5 patients with WPW syndrome, who at increasing rates until a rate was reached at least volunteered for the study after the procedure had as high as that observed during a clinical attack been fully explained to them and their consent of tachycardia. Recordings for measurements obtained. were taken about 45 to 6o seconds after the rate k was increased, to allow for the attainment of a steady state. After control measurements, 5 mg DL-tiprenolol (DU 2I445) was slowly injected intravenously in Cases I to 4. A second 'pace-run' at nearly identi- cal rate was then after minutes. In repeated I5 copyright. Cases 4 and 5, the effect of atropine administered CONTROt as a 2 mg intravenous dose I5 minutes after the it 1 4 I PH875 St-H 90 95 105 120 12S HBE :- v H /.. ' i-4i f I>;=/I H H: FIG. I Case I. the http://heart.bmj.com/ Tracings showing effect of I 1v progressively increasing atrial pacing rates in I.. WPW The His bundle syndrome. electrogram RATE 61 671 901 10 (HBE) is recorded simultaneously with leads St- d 1201 130 1i3 125 st-s 130 130 1301 136 II and VI. As the rate is increasedfrom 67 2201 230 2351 245 -11.255 260 .-, :- -, to a -- "- w 138 beats minute, there is a prolongation It ",-11. ." ".--el. - 1.11' 1. .., ." .I., -II/ of the time intervals between the P waves and ,.:r f I St-H 140 .. His spikes (PH intervals) and between the HtBE *w ,,,o, j pacemaker artefacts and His spikes (StH -. on September 24, 2021 by guest. Protected intervals) from 75 to 140 msec. At higher f S pacing rates, the His spike is hidden within the ;i i I I ! 'sf QRS complex. The intervals between the pace- vi i maker impulse and the delta wave (Std) do not /: w 5* .S t } change and remain constant at 130 msec. The RATE StS interval (which indirectly reflects the QRS 138 15D, 162 176 180 St-d 130 130 1301 1301 1301 130 duration since the Std interval is constant: St-s 285 275si 2B0 280 280 QRS width (StS)-(Std)) lengthens pro- ,. F gressively until a pacing rate of i5o beats a St ... HOE :. .1.... minute is reached. Pre-excitation becomes .l. .. .I '-progressively greater with increasing heart rates because of the decreasing contribution to ven- i tricular excitation via the normal pathway. At t j. # .- &s pacing rates higher than I62 a minute to 222 s. VI , a minute, the StS interval remains constant at ' 280 msec, and ventricular activation is effected RATE 167 * vkf200| 207 ~ 215~ 222 the St- d 130 exclusively by bypass impulse resulting in l30 130 130! 1301 130 a total pre-excitation complex. St-S 2601 2801 i...............28asr _, I 280 28 280 Br Heart J: first published as 10.1136/hrt.34.12.1272 on 1 December 1972. Downloaded from 1274 Roelandt, Schamroth, and Hugenholtz Case i This was a 40-year-old man who suffered AFTER DU 21445 5mg IV from attacks of paroxysmal tachycardia for i8 - "--' years. He had experienced at least one attack a " .' -, ""i'_1 _-e . : 55X -, week during the preceding two years. These PHHB "901 attacks occurred at a rate of about 220 beats a .N- s 12S 140 1 155 HB ... ... ... minute and were accompanied by dizziness and HI,% ; e. faintness. They lasted for periods ranging from I0 to 6o minutes. Clinical and laboratory examina- H f :. t tA tions were entirely normal. The basic electro- VI }, } cardiographic pattern revealed sinus rhythm and ,1 type A, WPW syndrome. ...,.i RATE 64 70 77 84. 88 96 Case 2 A 17-year-old man had complained of St-d 130. 140 140 404 40 135 action St-S 220 230z 250 85 m 280 intermittent attacks of rapid heart during oo, Ab * _. .. .R. s .. M. S .. the preceding three years, the frequency of which .S Ej had increased during the previous few months. w-. Clinical and laboratory examinations were normal. HOE ..*. .n * I, ; The electrocardiogram showed sinus rhythm and t * A '. 1. type A, WPW syndrome. b -? t _j man who had ! Case 3 This was a 67-year-old VI t 11 :, e. i e. I occasional attacks of rapid heart action for 50 v i.,? years. These had become more frequent and were RATE 100: 107 113 122 136 140 accompanied by angina pectoris during the pre- St-4d 140~ 140 140 13 5SE 1401 145 ceding year.
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