PROCAINE is an effective antifibrillatory

Transcription

1 The Intaton of Ventrcular Tachycarda and Fbrllaton n Isolated Hearts by Potassum Chlorde By L. GRUMBACH, PH.D. n collaboraton cth L. K. Tanner, B3. and J. Wybert, A.M. An acceleratng tachycarda endng n fbrllaton can be ntated n solated hearts by njectons of KC after the admnstraton of epnephrne, but not n untreated hearts. KC acts n two ways to do ths. Frst, t causes an A-V block that enables epnephrne to cause a paroxysmal ventrcular tachycarda. Secondly, t causes the latter to accelerate by delayng the recovery of exctablty so that at least one premature systole can fall nto the recovey phase of a precedng mpulse. Ths event s necessary and suffcent for the ntaton of a self-sustanng acceleratng tachycarda that can end n fbrllaton. PROCAINE s an effectve antfbrllatory agent, as shown by sutable tests n expermental anmals and, n addton, has been successfully used clncally for ths purpose. 2 However, n certan crcumstances t can cause ventrcular arrhythmas, both n expermental anmals 3 and n solated hearts. 4 The mechansms nvolved n ths acton of procane have been analyzed n the latter case. 4 In order to determne whether these mechansms are pecular to antfbrllatory agents of the local anesthetc type, the ablty of potassum salts to ntate ventrcular arrhythmas n solated hearts has been studed. They have long been known to have antfbrllatory actons 6 and to cause ventrcular fbrllaton n ntact anmals. 8 METHODS The electrcal actvty of solated rabbt hearts perfused wth Krebs-Henselet soluton n a Langendorff apparatus was recorded by a prevously descrbed method. 7 Epnephrne solutons were made up n per cent ascorbc acd to prevent oxdaton. The vehcle alone had only a transent effect on the T wave whch n control experments was found to have no bearng on the phenomena to be descrbed. KC n a 0.77M soluton was used for producng rapd alteratons n the K + concentraton of the tssue flud. From the Pharmacology Secton, Sterlng- Wnthrop Research Insttute, Rensselaer, N. Y. Receved for publcaton December 4, 955. RESULTS Injectons of KCl nto the perfuson stream never produced ventrcular arrhythmas when the hearts were well washed wth perfuson flud. The typcal sequence of events caused by a KCl njecton s shown n fgure, part la and conssts of a slowng of the snus rate and of atroventrcular and ntraventrcular conducton. The latter s more clearly seen n fgure 2, part 26 whch shows the lengthened P-R nterval and wdened QRS complex produced by KCl. These effects are entrely smlar to those produced by procane whch are shown n fg. 2, part 6 and fgure 2, part lc. In hearts that have been treated wth epnephrne, on the other hand, KCl njectons can cause an acceleratng ventrcular tachycarda that more or less rapdly ends n fbrllaton. The fbrllaton shown n part 2a of fgure contnued for 5 mnutes at whch tme t was stopped by an njecton of 0.8 ml. of 0.77M KCl. That shown n part 3 of fgure ended spontaneously a short tme after t began. In general, spontaneous reversons occurred wthn a mnute; past that tme, fbrllaton usually contnued ndefntely untl stopped by some antfbrllatory treatment. When ths was done, a normal snus rhythm was resumed (cf. part 26 wth 6 of fgure ). Certan characterstc effects of rapd KCl njectons on the electrocardogram were noted. One effect was the producton of A-V blockade 293 Cmulalon Rnearet, Volume I V, Mag t8m

2 VENTRICULAR FIBRILLATION BY POTASSIUM CHLORIDE 294 F O Of O.77M KCI OmV Control.0 sec. Imn. after I Omg epnephnne OmV 0.2CC of 0 77MKCI I OmV FIG.. Effects of KCI alone and after epnephrne. Dscussed n text. both n normal and n epnephrne-treated hearts, as can be seen n parts la, 2a and 3 of fgure. Ths also occurs wth procane njectons (fg. 2, part 6). A second effect that was seen only n epnephrne-treated hearts was the occurrence of premature ventrcular systoles. These made ther appearance coupled to the frst supraventrcular mpulses to pass the depressed A-V node. They are ndcated at the arrows n parts 2a and 3 of fgure. The runs of acceleratng ventrcular tachycarda produced by KCI njectons after epnephrne appear to consst on analyss of fast records of a seres of premature ventrcular systoles coupled to the frst and apparently emanatng from the same focus gvng rse to the frst one. The rapdty wth whch the ventrcular tachycarda accelerates and ends n fbrllaton depends on the amount of KCI used. Wth larger amounts of KCI the oscllatons are ntally slow and regular and ther acceleraton s gradual (part 3 of fg. ). Wth smaller amounts the acceleraton s more rapd and fbrllaton supervenes more quckly (part 2o of fg. ). The results just descrbed Avere obtaned n two out of every three hearts (the total number studed was 2). The negatve result was usually an abortve tran of premature systoles whch nonetheless was not counted as successful. However, n some hearts treated wth epnephrne the only effect of KCI was to slow the "ate and conducton as descrbed for untreated hearts at the begnnng of ths secton. KCI was also tested for ts ablty to replace epnephrne n the epnephrne-procane sequence of njectons that leads to an acceleratng ventrcular tachycarda endng n fbrllaton.4 The procedure was the same as that just descrbed for the epnephrne-kcl sequence. Part 2o of fgure 2 shows the effect on the electrocardogram 25 seconds after an njec-

3 GRUMBACH 295 p. I sec >4cc 2 % procane "0. sec 25sec after 0.2cc of 0.77M KCI 0.4cc 2 % procane Ill!r l!f 6mn after I.Omg/L atropne sulfate I I O.I sec I L f. r >.C)n 0.4cc 2 % procane ' I 25sec after loqug acetylcholne I f I.OmV FIG. 2. Effects of procune njectons alone and after KCI njecton. Dscussed n text. ton of 0.2 ml. of 0.77M KCI soluton. Record 2b demonstrates the effect of 0.4 ml. of 2 per cent procane soluton gven 5 seconds later. Record 2c, taken 20 seconds later, shows a seres of rregular doventrcular beats followed by a regular acceleratng tachycarda whch ended abruptly, as shown n 2e, 65 seconds later. The electrocardograms of the reverted beats 5 seconds afterwards (2/) showed that that heart was stll depressed by the combned effect of excess K+ and procane. The strongly depressant effect of the combnaton of procane wth excess K+ was undoubtedly responsble for the fact that the result shown n part 2 of fgure 2 was hard to obtan. Part 3 of fgure 2 shows that acetylcholne can also substtute for epnephrne n the epnephrne-procane sequence of njectons f the heart s atropnzed. The acceleraton of the snus rate and the appearance of a U deflecton n the ventrcular complex seen n part 36 mdcates that a consderable amount of a sympathommetc substance M'as released. In parts 3c, d, e t can be seen that enough was lberated to allow procane to

4 29C VENTRICULAR FIBRILLATION BY POTASSIUM CHLORIDK ntate ventrcular tachycarda and fbrllaton n the usual manner. DISCUSSION The results of KCl njectons n epnephrnetreated hearts are entrely analogous to those obtaned wth procane njectons n the same crcumstance. The frst acton of both substances n ntatng ventrcular tachycarda and fbrllaton s the producton of some degree of A-V block whch allows a latent acton of epnephrne to become manfest, namely, that of ntatng premature ventrcular systoles ether sngly or n trans of constant frequency.'* A second acton of procane and KCl s to transform ths paroxysmal tachycarda nto an acceleratng one. Fbrllaton occurs when the latter reaches a crtcal frequency. The essental feature of ths second acton of KCl s that recovery of exctablty s delayed wthout a concomtant decrease n the frequency of the premature ventrcular systoles. As a result successve mpulses fall nto the recovery phase of the mpulses just precedng each one. Ths s suffcent for the acceleraton of a paroxysmal tachycarda and the eventual ntaton of fbrllaton. The concept developed here, that KCl can only produce an acceleratng ventrcular tachycarda and fbrllaton n hearts that have been treated wth epnephrne and that t does so n ths crcumstance by depressng conducton and recovery of exctablty, does not accord fully wth older nterpretatons of the mechansm of K+ fbrllaton n expermental anmals. 8 ' 9 In some cases the njecton of KCl followed by a sutable amount of procane caused an acceleratng ventrcular tachycarda. Our nterpretaton of ths result s that KCl caused the release of an epnephrne-lke substance from the chromaffn tssue of the heart. Hoffmann and hs collaborators 0 showed that measurable amounts of such a substance were released when acetylcholne was njected nto solated, atropnzed hearts. SUMMARY The ablty of KCl to ntate ventrcular arrhythmas was studed electrocardographcally n solated rabbt hearts perfused wth Krebs-Henselet soluton n the Langendorff apparatus. In about two-thrds of the hearts studed, an acceleratng ventrcular tachycarda could be ntated by njectons of KCl nto the perfuson stream after treatment of the hearts wth epnephrne, but not n untreated hearts. In the majorty of cases the tachycarda ended n a transent or persstent fbrllaton. The mechansm by whch KCl produces ths result s entrely smlar to the mechansm by whch procane effects the same result n smlar crcumstances. Frst, t causes an A-V block whch permts epnephrne to ntate a paroxysmal ventrcular tachycarda. Secondly, t transforms the latter nto an acceleratng tachycarda by delayng the recovery of exctablty so that at least one epnephrnenduced premature ventrcular systole can fall nto the recovery phase of a precedng mpulse. KCl can also replace epnephrne n the epnephrne-procane sequence of njectons that leads to the ntaton of ventrcular tachycarda and fbrllaton. Evdence was adduced to support the vew that ths exctatory effect of KCl s an ndrect one, beng on ntracardac adrenergc structures and not on cardac tssue proper. SUMMARIO IN INTKHLINGUA Le capactate de chlordo de kalum de ntar arrhythmas ventrcular csseva studate electrocardographcamente n solate cordes de conlo perfundte con le soluton de Krebs- Henselet n le apparato de Langendorff. In crca duo tertos del cordes studate, l esseva possble ntar un tachycarda ventrcular acceleratve per njcer chlordo de kalum n le currente perfusonal post que le cordes habeva esste tractate con epnephrna. In cordes non ass tractate le mentonate effecto non se produceva. In le majortate del casos le tachycarda se termnava n un fbrllaton transente o persstente. Le mechan8mo per que chlordo de kalum produce ste effecto es ntegrementc smle al mechansmo per que procana effectua le mesme resultato sub smle condtones. Prmo,

5 GRUMBACH 297 llo causa un bloco atro-ventrcular que permtte al cpnephrna de ntal' un tachycarda ventrcular paroxysmal. Secundo, llo transform le tachycarda ventrcular paroxysmal n un tachycarda acceleratve per retardar le recuperaton del exctabltate de manera que al mnus un prematur systole ventrcular nducte per epnephrna occurre n le phase de recuperaton del mpulso precedente. Chlordo de kalum pote etam prender le placa de epnephrna n le sequenta de njectones de epnephrna e procana que duce al ntaton de tachycarda e fbrllaton ventrcular. Es presentate datos n supporto del concepton que le eftecto exctator de chlordo de kalum es un effecto ndrecte que age super structuras adrenergc ntracardac e non super hstos cardac per se. REFERENCES DAWKB, S. C: Expermental cu-duc arrhythmas and qundne-lke drugs. Pharmacol. Rev. 4: 43, 952. SCHERF, D.: Treatment of cardac arrhythmas. Crculaton 8: 7.50, 953. LONG, J. H., OPPENHKIMER, M. J., WESTER, M. R., AND DUKANT, T. M.: The effect of ntnvenous procune on the heart. Anesthesol. 0: 406, GRUMBACH, L.: The ntaton of ventrcular tachycarda and fbrllaton by procane n the solated, perfused rabbt heart. Crculaton Research 4: 2, 956. 'HBRING, H. E.: Ueber de Wrksamket des Accelemns auf de von Vohofen abgetrennten Kammern solrter Saugetherherzen. Zentmlbl. f. Physol. 7:, : Uber er'egende Wrkungen des Kalum auf das Sugetherherz. (Extrasystolsche Tachykarde, Flmmem.) Pflger's Arch. ges. Physol. 6: 544, 95. 'GRUMBACH, L., HOWARD, J. W., AND MERRILL, V. I.: Factors related to the ntaton of ventrcular fbrllaton n the solated heart: Effect of calcum and potassum. Crculaton Research 2: 452, NAHUM, L. H., AND HOFF, H. E.: Observatons on potassum fbrllaton. J. Pharmacol. & Exper. Therap. 65: 322, 939. ' WIGGKRS, C. J.: Studes on ventrcular fbrllaton produced by electrc shock. III. The acton of antagonstc salts. Am. J. Physol. 93: 97, HOFFMANN, F., HOFFMANN, E. J., MIDDLKTON, S., AND TALF.SNIK, J.: The stmulatng effect of acetylcholne on the mammalan heart and the lberaton of an epnephrne-lke substance by the solated heart. Am... Physol. 44: 89, 945.