Document m56qoEymzexrjNpXzm7jQBGJ

? w t ANESTHESIA XXXIV. Chemical Constitution or Hydrocarbons and Cardiac Automaticitt1 c. JELLEFF CARR, RAYMOND M. BURGISON, JAMES F. VITCHA, and JOHN C. KRANTZ, Jn. pertinent of Pharmacology, University of Maryland, School of Medicine, Baltimore, Md, Received for publication April 29, 1949 jn a former communication (1) the authors demonstrated that eleven cyclic gpd acyclic hydrocarbons, when inhaled, sensitized the dog's myocardium to epinephrine. On the other hand, in twelve animals ethylene failed to produce jpnsitization under varying experimental conditions. Thus it appears that ethylyje is unique, in this regard, among the hydrocarbons studied by us and also by Chenoweth (2). It is known that the aliphatic ethers as a class of anesthetic agents do not produce this type of myocardial sensitization. However, the unsaturated hydro carbon, ethylene, appears to behave in this respect similar to the aliphatic ethers dd diaaimilar to the hydrocarbons. It is the purpose of this investigation to pursue further the relationship between chemical constitution and myocardial sensitization to epinephrine. Compounds studied. Consideration was given first to inner oxides of hydro carbons; such molecules as ethylene oxide and propylene oxide have structural properties common to the hydrocarbons and the ethers. Certain rare cyclic hydrocarbons, such as methyl cyclobutane, were included. Spiropentane, owing to its relationship to cyclopropane, was studied. In addition, acetylene was tested to determine whether or not it behaved like its more saturated analog, ethylene. Experimental frocidurx. Electrocardiograms, Lead II, were recorded from the un&nesthetiied dogs. Epinephrine hydrochloride solution, 1:100,000 (preserved with sodium bisulfite), was injected intravenously, 0.01 rngm-Acm- The injection was made during a period of 25 to 40 seconds. At the end of the injection (usually the beginning of the effect) mother tracing was made. Subsequently each animal was permitted to breathe a mixture of the hydrocarbon in varying concentrations mixed with oxygen. With the liquid hydrocarbons the concentra tions were between 10 and 25 per cent. With the gaseous compounds concentrations from 15 to 90 per cent were used. The closed circuit procedure was employed. When the in halation had continued for from 10 to 20 minutes the foregoing experimental procedures were again carried out. Results. The various compounds studied and the results observed are shown in table 1. Discussion of results. In the dog, prior to the inhalation of the compound, 1 The expense of thie investigation was defrayed in.part by a grant from The Ohio Chemical & Mfg. Co., Cleveland, Ohio. 1 2 CARR, BUKGI50N, VITCHA, AND KRANTZ HYDF epinephrine produced slowing of the cardiac rate, accentuation of the and an occasional inversion of the QRS-complex. Under the infli]pnce ^,11 hydrocarbons producing sensitization, however, multifocal ventricular tachycardia occurred in nearly all experiments. In some animals this passed! ventricular fibrillation and caused death. From the data in table 1 it will be observed that acetylene was incapable^ producing sensitization similar to that produced by saturated hydrocarbons | In these dogs, exposure to acetylene1 was more comparable to exposure to etL ene that to other hydrocarbons. In four of the twelve animals some sensitizatK occurred, as evidenced by only a tachycardia with occasional arrhythmia j not ventricular fibrillation. Three of the twelve dogs exposed to acetylene exposed to cyclopropane on subsequent days. Not any of the three showed arrhythmias with epinephrine under acetylene; all three showed mu focal ventricular ectopic tachycardia with epinephrine under cyclopropane.! TABLE 1 KAMB Of COMWW* XUWM A)mgAX4 Of Bmi csMssmAttoii ormrocAiDnnc oca axo annaut vne Vinyl Chloride.............................................................................. Ethyl Chloride.................,........ *......... ............................. .. Methyl Cyclobutene,................ ...................................... 4/12 0/8 0/2 . 0/2 2/4 3/7 5/6 1/3 2/1 It appears that among the hydrocarbons, unsaturation reduces the incid of myocardial sensitization. Thus exposure to ethylene (1) in our experience < not sensitize the dog's myocardium to epinephrine. Nevertheless the introdu tion of a methyl group into the molecule with the formation of propylene, pn3 duced marked cardiac sensitization when inhaled. Similarly, acetylene produoadj only mild cardiac sensitization in certain animals with epinephrine. In three ani^ male the inhalation of methyl acetylene produced marked arrhythmias and i fibrillation without the injection of epinephrine. By examination of the data in table 1 it is observed further that sensitization with ethyl chloride was produo more often than with vinyl chloride in the eight animals studied. Garb and Chenoweth (3) conducted their studies on the papillary muscles ofj the cat's heart. We considered it of interest to study the cat's heart under etl ene anesthesia in order to include another species. Accordingly, we anesthetized] eight cats (eleven experiments) with ethylene-oxygen mixtures and subject them to the experiment. Like the dog, they did not show sensitization. * "Airco" acetylene wee purified by washing with water, concentrated sulfuric acid i 20 per cent sodium hydroxide solution, respectively. Garb and Chenowetl j^ntrations of the hyd of the ventricles, of certain sympathomii myocardial irritability with saturated coi rfects of sensitization it ^jth acetylene, sensitiz when this hydroc It appears therefore double and triple bondr However, failure to sent absence of some inciplei ' nations with various drt ^saturated hydrocarbour ''myocardial sensitization oration in the molecuk 1. The capacity of act 'Vppeaxs to be interned: 2. Ethylene failed to 3. It appears that v less frequently than doc fc'*Acknowledgement. H. Oster, of the Depart the interpretation of tl r 1. Kiuntz, J. C., Jm., Cams . 2, Chenoweth, M. B.: J. 1 t. Gar*, S., and Chenowi ucc 023376 kraxtz , accentuation of the T-waxs' Under the influence of the nultifocal ventricular ectop* some animals this passed into #1 at acetylene was incapable of j y saturated hydrocarbons (2). nparable to exposure to ethyl*^ lve animals some sensitization th occasional arrhythmia ami ogs exposed to acetylene wen Tot any of the three anirnsh ylene; all three show ed multihrine under cyclopropane. nun imuu m __ 1 11* *unmunra o myocamdhm (Win*" AMS M JK S iration reduces the incident ene (1) in our experience*^ Nevertheless the introd*^ formation of propylene, Pjj ^ iimilarly, acetylene prodiMw ith epinephrine. In three & Larked arrhythmias and y examination of the dat*^ i ethyl chloride was produ<* .nimaills studied. ,j on the papillary muscle* | rLtchceeorcVdaHin,t'gs_l_yh_,e_wa_er_t u__n_der e*t"h"F| anesth1*^ .J ;en mixtures and subj4** show sensitization. , concentrated sulfuric ad HYDROCARBONS AND CARDIAC AUTOMATTCITT 3 and Chenoweth (3) have suggested the hypothesis that different con* lions of the hydrocarbon reduce myocardial irritability in various porof the ventricles. This gives rise to small temporary blocks in the presence [certain sympathomimetic amines. Our findings indicate that the changes in irritability are much less marked with unsaturated hydrocarbons with saturated compounds. Indeed we have failed to produce the classical of sensitization in any of twelve dogs or eight cats with ethylene. However, acetylene, sensitization of a minor degree was produced in four of twelve when this hydrocarbon was inhaled. appears therefore that sensitization of the myocardium is disfavored by lie and triple bonds between the carbon atoms in the inhalaH hydrocarbon, rer, failure to sensitize seems to be a matter of degree and not the absolute of some incipient effect. We have not been able to correlate theee obeerwith various differences in the physical properties of saturated and tin ted hydrocarbons. Nevertheless a distinct diminution in the degree at ial sensitization does appear to be associated'with the presence of unsat in the molecule. CONCLUSIONS --- capacity of acetylene to sensitize the dog's myocardium to epinephrine , ra to be intermediate between ethylene and saturated hydrocarbons. Ethylene failed to sensitize the heart of the cat to epinephrine, tit appears that vinyl chloride produces sensitization of themyocardium Jrequ--enittly than does its saturated analog, ethyl chloride. n'Owledgement. The authors wish to express their thantot to Dr. Robert r, of the Department of Physiology of this school, for his assistance in hterpretation of the electrocardiograms. REFERENCES , J. C., JR., Cabs, C. J., and Vitcha, J. F.: This Journal, 94:310,1948. R, M. B.: J. Ind. Byg. and Toxicol., 38: 151, 1940. L, amb Chsnowbth, M. B.: This Journal, 94: 13, 1948. IJCC 023377