Document nmDRV53qk9MXxKg8v8Jp4QYQa

THE 3IECH.AXISI OF SUDDES DE-ITH IS ESPERIMENTAL ACUTE BENZOL POISOSISG . L. H.N.4HL-31 .WD H. E. HOFF From lhe Laboratory of Physiology, Yale Cnirersily School o j Jlrdicinc Received for publication January 25,1934 It is a well established fact that exposure to the vapors of the coal tar distillate, benzol (CeHs),produces both acute and chronic poisoning and that the acute poisoning often terminates in death. More than half of the cases of benzol poisoning analyzed by the Benzol Poisoning Committee of the National Safety Council (1) terminated fatally. This report, as well as those of NcCord (2j and Hamilton (3), showed that low concentrations of benzol vapor often caused sudden death, while in other cases high con- centrations failed to do so. Bamesreiter (4) obtained similar results in an experimental study of acute benzol poisoning. Phys- ical exertion was also often associated with 3 fatal terminstion. In many instances members of a rescue party were fatally poi- soned while the original victims, sometimes unconscious for a considerable Deriod of time, survived. Finally it is necessary to point out that the emotional state of the gassed-person may have an imuortant bearing on the outcome in such cases. Such a typical cas; is cited by Feil (5) in which the 1icti.m burst sud- denly out of the space where he had been working, cried several times that he was burning and dropped dead. It seems difficult in the light of these observations to accept the view that sudden death in acute benzol poisoning ensues from respiratory paralysis, and consequently the present investigation was undertaken in an effort to find an explanation for these - hitherto unexplained facts. It was our belief that, in such cBses, cardiac and not respiratory failure might be a more logical cause of death. This opinion has been completely substantiated by thepresent investigation. - - . - ... 336 I .-__. 8.. . .. . . . These caca mc The ani at the I tion wv3 Coverc'I The connec benzol over iz turned the pe! Electn with tJ A. after sJ-sto1 branc in SU( not a with betJY the bum -- . - the nisn x nor] quic - con tior T 1 fad 335 L. H. S.\HTJI A S D H. E. HOFF ! .. - I FIG. 1. Experiment 60. Monkey (Mncncn mulatta). h y t a l anesthesia. Progressive anoxemia developing during benzol inhalation as shown by elevation and alteration of STsegment. A shortening of the P-R interval indicating downward shift of pacemaker. Flo. 2. A . E Adrcnals ~ O tricular ext- begreB. Ex rimt hours t C..Experimr ganglia remove nubDc.uEt axnperoidm!, rol immediatei Y .. ^. . I -. .. 310 L. H. S.\HC.\I . I S D H. E. HOFF .- FIG. 3. Experiment 37. Cat. Amytal anesthesia. A . Ventricular extra- Systoles from multiple foci following benzol inhalation. E . One-half cubic centimeter ndrenaline iiijected intrnvenously upon appear- ance of extrasystoles. Vcntricular tachycardin. C and D. Dewloprnent of vrntrirulsr fibriII3tioii in five minutes. artificial re: stage similz appearance of ventricl ventricular " henin! narcosis an displaceme -terminatin pleses. 1. anoxemia c B. Efec glands. 11 Levy and 1 ventricda chlorofom similar mi same type In thre foci yentr rend glor. hour or m ectopic bt they seen and did r After ren well eta precede abnormi phase bu C. E 8 dudion four bot animal T quickeni ance of interrup SZ-DDES DE.\TH IS .\CUTE BESZOL POISOSISG 341 r artificial respiration i ~ a ssuccessful, the animal passed through a stage similar to that occurring on induction, characterized by the appearance of multiplefoci ventricular extrasystoles or periods of ventricular tachycardia which occasionally terminated in ventricular fibrillation (fig. 3). When inhalation was continued through the induction stage of narcosis and the animal became deeply narcotized, a progressive displacement of the S-T segment was noticed in three experiments, terminating in complete disorganization of the QRS and T com- plexes. These changes (fig. 1) evidently indicate progressive anoxemia of the myocardium. B. Egect of benzol inhalation after removal of both suprarenal glands. Inasmuch as the r6le of adrenaline had been shorn by Le1-y and Lewis (6) to be of great significance in the production of ventricular extrasptoles and ventricular fibrillation during light chloroiorm narcosis, it seems desirable to determine whether a similar mechanism was responsible for the appearance of the same type of irregularities in acute benzol inhdation. In three experiments which showed characteristic multiple- foci ventricular extrasystoles when benzol was inhaled, both ad- renal glands mere removed. ,After a recovery period of 9 half- hour or more, benzol vapor was again administered. Ventricular ectopic beats quickly made their appearance. although at times they seemed less numerous than previously, arose from fewer foci, ~. and did not completely supplant the normal mechanism (fig. 2L - -. After removal of the adrenals benzol inhalation no longer led to well established ventricular tachycardia of the type kn0n.n to precede ventricular fibrillation. In one such experiment an abnormal rhythm failed to develop at all during the induction phase but appeared during the recovery period. C. Eflect of b i e a l .removal of the stellate ganglia on the pro- dudion of vent-r rhythms. I n one experiment typical of - . four both stellate ganglia were excised; and five hours later the. animal was exposed to benzol vapor. There was an immediate '. quickening of the rate, leading after one minute to the appear- ance of ventricular extrasystoles from two foci, frequently . interrupting the nonnd rhythm. Ventricular tachycardia did . - .-- -___._ 342 L. H. XAHUM AND H. E. HOFF not occur, although it had appeared regularly following benzol before the accelerantes were interrupted by stellate ganglionec- tomy. Excision of the stellate ganglia was in every case some- what less effective in preventing the appearance of ventricular. tachycardia than mas the removal of the adrenals (fig. 2, B). D. Remocal of both adrenal glands and the stellate ganglia. In three animals both the adrenal glands and the stellate ganglia were removed. In the first of these, where the benzol inhalation was begun before a half-hour after the operation, a few ectopic ventricular beats appeared. In the other two experiments the interval following the operative procedures was longer, and no ventricular rhythms occurred. In all three experiments, how- ever, there occurred a slight increase in the heart rate (fig. 2, C), a flatteningof the T wave, and a downward shift of the pacemaker. E. The eflect of decerebrdion. Further to eliminate the eEect of cerebral stimulation on the peripheral mechanism experiments were performed on four decerebrate cats. In every instance the inhalationof benzol vapor produced the characteristic ventricular rhythms obtained in the intact animal. F. The effect of benzol inhalation in animakr With hdrenals and steuate ganglia removed, before and after the injection of adrenaline. It was pointed out earlier that, after a sdicient interval folloning the removal of the adrenal glands and the stellate ganglia, inhala- tion of benzol vapor produced none of the ventricular rhythms characteristic of benzol inhalation in the intact animal. In experiment 62 (monkey), inhalation of benzol vapor in the intact animal gave rise to ventricular tachycardia of the type recognized aa prefibrillation. After both stellate ganglia and adrenals were removed inhalation of benzol led to an increase in rate but not to the occurrence of ectopic beats. A slight decrease in the P-R _ __-......*....-_-.-._...-.....-............. .. ____ ... i. --.- . interval from 0.08 to 0.06 second occurred. The animalwaa allowed to recover from the benzol vapor and 1.5 cc. adrenaline was then injected subcutaneously. The characteriatic cado-accelerator effects ware obtained, such as tachy- ......... . ..... cardia and shortening of the P-R-and QRS complexes. After an interval of ten minutes during which no other changes took - - . - - . place the rrdministration of benzol was begun, and was imme- .-....... SUDD diately follow( animal (fig. 2, and then fror adrenaline w2 acteristic ven tion (fig. 3). The appea: ments evider influence of k of suEcient influence of . rate, the flat pacemaker, glia. WE of adrenalin tricular tack are present The Liter accompany to that foc form anaez citement h. Such centr ine dischar for it hss produces E Beattie, E probably tall in blc end actio in the in liberatior myocardi These mechani: .- .-_. _. _. :..._.... . -..'.-.--T-.L_.... -...-.. --..........._....-_..._...-.-.....-.......-... ..I ...- . .--.-. .. - -. . .... ' *=ld 344 L. H. SAHZiY . i S D H. E. HOFF 9, o w muscuiar exercise in acute benzol poisoning so frequentlJcited in the literature. In muscular exercise there is a reflex cardio-acceleration (Bainbridge (ll)),with a liberation o sympathin (Cannon and Bacq (12)), while in excitement there is in addition to this a well marked liberation of adrenaline into the * blood stream. The adrenaline and sympathin contribute to the production of 1-entricularextrasystoles, and the amount liberated determines the severity of the attack. It is therefore probable that the individual variations in susceptibility to benzol poisoning frequently reported (Committee on Benzol Poisoning (1)) may be due largely to variations in the adrenaline response. In both the clinic21reports and in these experiments the danger of death from ventricular fibrillation occurs during the phase of induction or recovery from the narcosis; periods of hyperexcitability and increased adrenaline liberation. Sudden death is known to occur in many form of heart disease. It may well be that in some such cases, as in these studies, a sensitized heart has responded to the action of adrenaline by,the development of ventricular fibrillation. STJSSIL I R T * 1. Ten cats and two monkeys were exposed to'benzol vapor in high concentration. 2. In the intact animal such exposure invariably led to the appearance of ventricular extrasystoles and ventricular tachy- cardia of a pre-fibrillation type. These irregularities appeared during the period of induction or recovery. 3. The removal of the adrenal giands in three animalsreduced, but did not abolish, the ventricular extrasystoles, and the removal of both stellate ganglia in four cases was not effective in reducing the frequency of ventricular rhythms. ... .- . . . ..--,... . . . - . - 4. With the adrenal glands and the stellate ganglia both ex- -cised,-in three experiments, ventricular rhythms no longer ... appeared. They were immediately produced after the subcuta- ....~ . . ---.I. . . . . . .-..- . ,_ _ - _ - . - neous injection of adrenaline. When benzol was .such doses ofadrenaline had only cardio-accelerator not inhaled effects. . -05. During the stage of narcosis respiratory failure occurred .-..-. ... ..-...,. . .. ,.__m -. ...... . .. i... i. i. ...-.-...... ....-.-.... .. -..-...__._,_..._-.--_- ._......-*.--....-.-...---..- . . .-..... .-__......_. . - - . . . . . . . . . ._ . 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