Action Upon Isolated Neeve of Anesthetics, Sedatives, and Narcotics
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ACTION UPON ISOLATED NEEVE OF ANESTHETICS, SEDATIVES, AND NARCOTICS. A Demonstration at a Meeting of the Neurological Society, Downloaded from June 25, 1896. BY AUGUSTUS D. WALLER, M.D., F.E.S. I. —PBOPOSITIONS. http://brain.oxfordjournals.org/ (1) Anaesthetics, in small quantity, temporarily augment; in large quantity, temporarily or permanently depress or abolish the excitability of isolated nerve. (2) Carbon dioxide acts as an anaesthetic upon isolated nerve. Nitrous oxide has no appreciable action. (8) An isolated nerve ifl more safely anasthttised by ether than by chloroform. (i) There exists an apparent antagonism between chloroform and carbon dioxide as regards their action upon isolated nerve. (5) Bromides and other haloid salts exert a depressant action upon by guest on June 5, 2016 the excitability of isolated nerve. This depression depends upon the salt as a whole, more however upon its basio than upon its acid moiety, e.g., K Br is more depressant than Na Br ; Sr 01, is reviving ; Sr Br, is depressant. (6) There is a mutual antagonism between potassium chloride on the one hand, and caloium and strontium salts on the other. (7) Among alkaloids and other narcotics, some are depressant, others are inert, as regards an influence upon isolated nerve. Ctxteris paribus morphine, strychnine, muscarine, atropine, aconine, are inactive. Extract of opium, oocaine, aconitine, physostigmine, curarine, gelsemine, veratrine, ohloral hydrate, butyl chloral hydrate, are depressant. II.—EXPEBIHBNTAIJ DEMONSTRATION OP Proposition (3) Ether compared with chloroform. Proposition (5) K Br compared with Na Br (in deci-molecular solution). Proposition (7) An inaotive alkaloid (morphine) compared with an active alkaloid (aconitine). LH.—IiAHTKBN DEMONSTRATION of experimental records in evidence of Propositions 1 to 7. 570 ORIGINAL ABTICLES AND CLINICAL CASES. The regular procedure in taking records of the effeots of volatile reagents U as follows:— The nerve, laid upon exciting and leading off electrodes and enclosed in a moist chamber, is tetanised at regular intervals (onoe a minute) for one-eighth of a minute. The resulting " current of action " is photographically recorded. Measured quantities of air are driven through the reagent into the moist chamber, by means of a pressure-bottle, while the rhythmio excitation of the nerve is in progress. THE experimental records to be passed under review have been selected as being illustrative of three groups of Downloaded from reagents, viz., anaesthetics, sedatives, and narcotics. The first two plates are selected instances of normal runs, the first exhibiting deflections of declining magnitude, the second exhibiting deflections of constant magnitude. The deflections at the beginning and end of each series http://brain.oxfordjournals.org/ are standard deflections, by T^J volt sent through the nerve and galvanometer, and serving, therefore, to indicate the electromotive value of the negative variations. Throughout all my earlier experiments I obtained normal records of the first type, more or less pronounced. In later expeiiments I was usually able to obtain records of the second type. The latter type obviously affords the most favourable condition under which to test the effect of reagents ; never- by guest on June 5, 2016 theless experiments made upon nerves giving declining variations are by no means valueless, as indeed we shall have occasion to see (411). Clearly the first thing to do with such nerves was to test the action of anesthetics upon them. 552 is a typical chloroform effect, obtained by driving air into the nerve-chamber, for one minute, through a pair of wash-bottles, the first containing pure chloroform, the second water. The electrical response of the nerve is finally abolished. 576 is a typical ether effect, obtained by driving air into the nerve-chamber, for one minute, through a pair of wash- bottles ; the first containing anaesthetic ether, the second water. The electrical response of the nerve is temporarily sup- pressed. FIG. 1. Downloaded from http://brain.oxfordjournals.org/ After. N,0. Before Normal run of negative variations of declining magnitude at 1 minute intervals unaffected by gas not acting upon nerve (nitrous oxide). The general decline is due to the falling " current of injury." The deoline referred to in the text is of the magnitude of successive deflections. by guest on June 5, 2016 Fir.. •>. Normal run of negative variations of regular maguitude at 1 minute intervals. The general decline of the base line is not the decline referred to in the text, and is due to the falling " ourrent of injury." PIG. 3. (552) Downloaded from http://brain.oxfordjournals.org/ Before. Chloroform. After. FIG. 4. (676). by guest on June 5, 2016 Beiore. Ether After. Downloaded from PlQ. 5. (666) Weak Ether effect. http://brain.oxfordjournals.org/ by guest on June 5, 2016 Before. Et,O. After. Fio. 6. Downloaded from (669) Weak Chloroform effect. http://brain.oxfordjournals.org/ by guest on June 5, 2016 Before. After. Pia. 7. (674) Effect of "little" CO.. Downloaded from http://brain.oxfordjournals.org/ Before. CO.. Alkss, FIG. 8. by guest on June 5, 2016 (027) Effect of " much " CO5. Before. After. CO,. PlO. 9. (411) Absence of effect of Nitrous Oxide. Downloaded from http://brain.oxfordjournals.org/ NX). N,0. by guest on June 5, 2016 Fio. 10 (described in text). (205) (536) (200) (809) Fio. 11. (3055) Downloaded from (3056) http://brain.oxfordjournals.org/ FIG. 12. Aotion of Chloroform with and without Carbon Dioxide. 64'J 560 with) I (without) by guest on June 5, 2016 561 652 with) (without) —>• a. 13. Action of Ether and of Chloroform upon retinal excitability by light. Chloroform. (3046) Downloaded from Ether. (3049) http://brain.oxfordjournals.org/ FIG. 14. (410) Effect of Potassium Bromide. by guest on June 5, 2016 Before. A. After. KBr. tD/10 ACTION UPON ISOLATED NEBVB OP ANESTHETICS, ETC. 571 This is a representative contrast, exhibiting one of the most definite practical results of these experiments, and in view of its importance I wish to shew it to you as a going experiment. EXPERIMENT I.1 ACTION OF ETHER AND OF CHLOROFORM (and air saturated with vapour, i.e., with 60 % ether, and 12 % chloroform). Time. Deflection Time. Deflection. Downloaded from 0 min. —10-6 16 min. —14 1 „ —11-6 CH 01, 760 o.o. 17 ,, —12 2 „ —11-6 18 ,, —5 8 „ —11 of air through - 19 ,, —1 wash-bottle. 4 .. —11 20 , 0 6 „ —9 http://brain.oxfordjournals.org/ Et,0 1,000 o.o. 21 „ 0 6 „ —6 of air through 22 „ 0 7 „ —3 wash-bottle. 23 „ 0 8 „ 0 24 „ 0 9 „ 0 25 „ 0 10 „ 0 26 „ 0 11 >, —8 27 „ 0 12 „ —18 28 „ 0 13 „ —17 29 „ 0 H „ —16 30 „ 0 15 „ —16 120 .. 0 by guest on June 5, 2016 1 The numbers given in the protocols of experiments I., n. and m., are those actually noted at the meeting, with the exception of those in square brackets which were taken after its conclusion. In a series of rehearsal experiments made the day before the meeting, the numbers were as follows:— June 24, 1896. I . Ether and Chloroform. Time. Deflection. Time. Deflection. ft min —9 16 min. —10 1 „ -9 17 , —10 2 „ —9 18 , —10 oQ . —Oo 19 , —8 4 —7-6 20 , —8 6 , -7-5 21 , —8 6 , —7-5 Chloroform: 22 , —6-5 7 1 6OO0.0. air through 28 , —6 Ether: 700c.c 8 . -6 wash-bottle. 24 , —2 air through 9 wash-bottle. 10 26 , 0 :: =? 26 , 0 11 , —i 27 , 0 12 , —i 28 , 0 13 , -2 29 , 0 14 —8 30 , 0 15 , -10 90 , 0 VOL. XIX. 38 572 ORIGINAL ARTICLES AND CLINICAL CASES. H. Potassium Bromide and Sodium Bromide. First nerve. Second nerve. Time. Deflection. Time. Deflection. 1 min. —11 1 min. —9 2 „ —11 3 „ —9 8 „ —12 3 „ —9 Bath of KBr, m/» sol. Bath of NaBr, m/6 sol. for 10 min. for 10 min. 14 „ 0 U „ —9 16 „ 0 15 „ —9 Put aside in NaCl, Downloaded from m/io sol. for 2 hours. 136 „ —6 111 Morphine and Aconitine (same nerve as that used for NaBr). Time. Deflection. http://brain.oxfordjournals.org/ 0 min. —9 1 „ -9 2 „ -9 Bath of Morph. Hydrochl. 1 °/o sol. for 1 min. i „ -12 6 „ —12 Bath of Aconitine Hydroohl. 1 °/o sol. for 1 min. 7 i> —8 by guest on June 5, 2016 8 „ —3 9 „ 0 10 ., 0 While this experiment is in progress, we may examine the records selected in evidence of Propositions 1 and 2. If, instead of blowing air through pure chloroform or pure ether in the wash bottle, we send it through chloroform and water, or ether and water, an immediate augmentation of the nerve-response is produced, more easily indeed in the case of ether, which even undiluted sometimes produces this effect. 556. Weak ether effect. 669. Weak chloroform effect. The primary augmentation is evidently more marked in the case of weak ether than in that of weak chloroform ; and another point of difference in my hands has been that a nerve emerging from ether anesthesia frequently exhibits a ACTION UPON ISOLATED NERVE OF ANESTHETICS, ETC. 573 secondary augmentation, which I have never seen in the case of chloroform. Carbon dioxide, which has sometimes ranked clinically as an anaesthetic, has, in these experiments upon isolated nerve, behaved in a typically anaesthetic manner. Whereas nitrous oxide, which clinically is admitted to be an anaesthetic, tested under similar conditions, has proved to be totally inert. Downloaded from The inference is so obvious that I may expressly forbear to draw it, leaving you to judge, as you may think fit, the experimental data in point.