Influence of the vagus nerve upon the reflex control of the lower oesophageal sphincter

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1 Gut, 1984, 2, Influence of the vgus nerve upon the reflex control of the lower oesophgel sphincter L OGILVIE* ND M TKINSON From University Hospitl, Queen's Medicl Centre, Nottinghm SUMMRY In 24 control ptients the lower oesophgel sphincter responded to grded increments in intr-bdominl pressure by significnt nd sustined rise in tone. This response ws bolished by tropine nd ws lso bsent in nine of 11 ptients who hd previously undergone truncl vgotomy for duodenl ulcer but not in the remining two who hd recurrent ulcertion. In six ptients studied fter proximl gstric vgotomy vrible response ws seen. Gstric efferent vgl function ws ssessed by combined insulin/pentgstrin gstric secretory test nd did not correlte closely with the lower oesophgel sphincteric response to incresed intr-gstric pressure. These findings re explicble if it is ssumed tht truncl vgotomy interrupts the fferent limb of reflex rc regulting lower oesophgel sphincteric tone. Lower oesophgel sphincter pressure hs been shown to increse with rise in intr-bdominl pressure' 2 nd this my represent n importnt mechnism protecting ginst gstro-oesophgel reflux. Whether the vgus nerve is concerned in the reflex control of the lower oesophgel sphincter is uncertin nd while some hve found tht truncl vgotomy bolishes the sphincteric response to increse in intr-bdominl pressure,3 4 others hve filed to do so nd hve suggested the pressure increse is brought bout by diphrgmtic contrction. To investigte the possible role of the vgus in the reflex control of the lower oesophgel sphincter, we hve studied the effects of tropine nd of truncl nd proximl gstric vgotomy upon the response of the lower oesophgel sphincter to increse in intr-bdominl pressure. Methods PTIENTS The control group consisted of 24 ptients (21 men) with men ge of 43 yers (rnge 3-7 yers), who hd undergone upper gstrointestinl fibreoptic endoscopy for dyspepsi. Eighteen hd chronic ddress for correspondence: Dr M tkinson, University Hospitl, Queens Medicl Centre, Nottinghm NG7 2UH Received for publiction 21 June 1983 * Present ddress: Gstrointestinl Unit, Western Generl Hospitl, Crewe Rod, Edinburgh. duodenl ulcer nd in six no bnormlity ws found. ll ptients were judged to be free of oesophgel disese fter rdiologicl, endoscopic, oesophgel mucosl biopsy, oesophgel motility, nd oesophgel cid perfusion studies. Eleven ptients (1 men) with men ge of 48 yers, (rnge 34-2 yers), who hd undergone truncl vgotomy for chronic duodenl ulcer were studied. Two hd recurrent duodenl ulcer nd four hd postvgotomy complictions (biliry gstritis in two nd reflux oesophgitis in two). Six ptients (five men) with men ge of 43 yers (rnge 23-4 yers), who hd undergone proximl gstric vgotomy were lso studied. None of this group hd evidence of recurrent duodenl ulcertion. The investigtion ws pproved by the ethicl committee nd ll ptients gve their informed consent to tke prt. MESUREMENT OF LOWER OESOPHGEL SPHINCTER PRESSURE The pressures were recorded through triple lumen polyvinyl tube (outer dimeter 3- mm, inner dimeter of ech lumen 1 mm) which hd three lterl orifices situted t the sme horizontl level nd rdilly orientted t intervls of 12. Ech lumen ws perfused with wter t rte of -8 ml/min from motor driven gresed glss syringe nd ws connected vi trnsducers to n ultrviolet recorder. The system hd mximum rte of 23 Gut: first published s 1.113/gut on 1 Mrch Downloded from on 1 September 218 by guest. Protected by copyright.

2 24 response of 9 mmhg/sec nd n ccurcy over the rnge of to mmhg of ±2 mmhg. t the beginning of ech study clibrtion ws mde ginst column of mercury nd the tmospheric pressure ws recorded with the trnsducers plced horizontlly t the level of the nterior xillry line. Ptients were studied fsting in the supine position. fter 1 minute resting period the level of the lower oesophgel sphincter ws identified by withdrwing the tube in 1 cm steps nd recording for 1 seconds t ech level. The lower oesophgel sphincter pressure ws then mesured by the rpid pull through technique by withdrwing the tube through the previously identified sphincter t rte of 1 cm/sec with the ptient holding his breth in expirtion. Ech reding of lower oesophgel sphincter pressure represented men of 1 vlues obtined by five pull throughs of the recording tube. thigh sphygmomnometer cuff ws then bound to the nterior bdominl wll nd inflted in increments of 1 mmhg to mximum of 1 mmhg or until the ptient ws unble to tolerte the pressure. t the end of the procedure the cuff ws removed nd resting lower oesophgel sphincter pressure ws gin recorded. Intrgstric pressure ws tken s the difference between the fundl pressure nd tmospheric pressure nd the increse in intrgstric pressure with bdominl compression ws obtined by subtrcting the resting intrgstric pressure from the intrgstric pressure recorded t ech cuff pressure. Lower oesophgel sphincter pressure ws tken s the difference between the mximum pressure in the sphincter nd the intrgstric pressure using the men of 1 redings tken t ech level of pressure in the bdominl cuff. The increse in intrgstric pressure ws not closely relted to the level of pressure in the cuff nd vried between individuls depending upon the resistnce of the nterior bdominl wll. For this reson chnges in lower oesophgel sphincter pressure were recorded in reltion to chnges in intrgstric pressure rther thn the indicted pressure in the cuff. GSTRIC SECRETORY STUDIES Gstric secretion ws studied fter n overnight fst. phenol red mrker ws used to correct for collection errors nd pyloric losses7 nd electrolyte concentrtions of gstric juice were mesured to correct for swllowed sliv nd duodenogstric reflux.8 The rtio of the pek cid output fter insulin induced hypoglycemi (blood sugr concentrtion less thn 2 mmol/l) to the mximl cid output fter pentgstrin (,ug/kg body weight) ws used to ssess the sttus of vgl efferent fibres to the stomch.9 STTISTICL METHOD Ogilvie nd tkinson The t test for pired dt ws used to compre the lower oesophgel sphincter pressure mesurements within individuls. Results EFFECT OF BDOMINL COMPRESSION UPON LOWER OESOPHGEL SPHINCTER PRESSURE In ll groups there ws close correltion between the vlues of resting lower oesophgel sphincter pressure obtined before infltion of the bdominl cuff nd those fter its relese (r=.9; p<-1). The men resting intrgstric pressure nd the men resting lower oesophgel sphincter pressure did not differ between the control ptients nd those who hd undergone truncl vgotomy or proximl gstric vgotomy (Tble). In the control group increse in intrgstric pressure with bdominl compression resulted in significnt nd sustined rise of lower oesophgel sphincter pressure (Fig. 1). The rise in lower oesophgel sphincter pressure ws pprent with reltively smll increses in intrgstric pressure of up to 3 mmhg nd with further increses of intrgstric pressure, lower oesophgel sphincter pressure rose proportiontely less. Eight of the control ptients were given tropine (.1 mg/kg body weight subcutneously) nd the study ws repeted. lthough the resting vlues of intrgstric pressure nd lower oesophgel sphincter pressure before nd fter tropine in these ptients were comprble (Tble) the lower oesophgel sphincter pressure response to increse in intrgstric pressure ws bolished by the drug (Fig. 2). In those ptients who hd undergone truncl vgotomy, increse of intrgstric pressure did not result in ny increse in lower oesophgel sphincter pressure nd indeed there ws tendency for this to fll (Fig. 3). Five of these ptients were given Tble Men resting intrgstric pressure nd men resting lower oesophgel sphincter pressure in ptients hving undergone truncl vgotomy or proximl gstric vgotomy Resting lower Resting oesophgel Ptients intr-gstric sphincter Group (no.) pressure (mmhg) pressure (mmhg) Controls 24 9 ± ± 79 pre-tropine 8 9-1± ± 81 posttropine 8 9-2± ±-89 Truncl vgotomy ±-7 119± 1. postcrbchol 1-4± Proximl gstric vgotomy Gut: first published s 1.113/gut on 1 Mrch Downloded from on 1 September 218 by guest. Protected by copyright.

3 Influence of the vgus nerve upon the reflex control of the lower oesophgel sphincter Fig. 1 Response of lower oesophgel sphincter (LOS) pressure to incresing intrgstric pressure in 24 controls. Points re mens ± SEM. Dotted line indictes resting lower oesophgel sphincter pressure nd significnt chnges re indicted (* p<1; ** p<o-.oo)., E u) Lii CL G7) crbchol (4,ug/kg body weight subcutneously). lthough crbchol cused rise in the resting lower oesophgel sphincter pressure (Tble) there ws no further increse with bdominl compression. In the six ptients who hd undergone proximl gstric vgotomy the chnge in lower oesophgel sphincter pressure with incresing intrgstric pressure ws vrible nd rise ws found in three of the six ptients. The rise in lower oesophgel sphincter pressure ws not proportionl to tht of intrgstric pressure nd fter n initil increse, lower oesophgel sphincter pressure tended to form plteu s Increse in intrgstric pressure (mmhg) intrgstric pressure ws incresed further, thus mintining reltively constnt grdient between pressure in the stomch nd tht in the sphincter. To illustrte the vribility between individul ptients in ech group the mximum rise of lower oesophgel sphincter pressure during bdominl compression is shown in Fig. 4. In the control group of ptients this rnged from 2*-9 mmhg but fter tropine never exceeded 1-4 mmhg. In only two of the 11 ptients who hd undergone truncl vgotomy did the rise in lower oesophgel sphincter pressure lie within this rnge nd these were the two ptients with recurrent ulcertion. In the other nine, lower oesophgel sphincter * 2 Gut: first published s 1.113/gut on 1 Mrch Downloded from Fig. 2 Effect of tropine on the lower oesophgel sphincter (LOS) pressure response to incresing intrgstric pressure in eight controls. Points re mens ± SEM. The response -before tropine is shown by nd response fter tropine by. Dotted line represents resting lower oesophgel sphincter pressure nd significnt chnges re indicted (* p<-; ** p<o-oi). 7 r z4 EE 3 T) Ln.- - (-._ ; Increse in intrgstric pressure (mmhg) on 1 September 218 by guest. Protected by copyright.

4 2 Fig. 3 Response oflower oesophgel sphincter (LOS) pressure to incresing intrgstric pressure in 13 ptients fter truncl vgotomy. Points re mens ± SEM. I E 2 pressure fell with bdominl compression. Of ptients who hd undergone proximl vgotomy, three recorded norml rise in oesophgel sphincter pressure; while in the three, lower oesophgel sphincter pressu during bdominl compression. GSTRIC SECRETORY STUDIES Gstric secretory studies were done in 1 control group of ptients nd in ech the Fig. 4 Mximum chnge in men lower oesophgel sphincter (LOS) pressure in the vrious groups studied. the solid horizontl line indictes the resting lower oesophgel sphincter pressure nd the dotted horizontl line represents the lower limit ofthe norml response to incresing intrgstric pressure. () C ' 4 Increse in intrgstric pressure (mmhg) CD I EE V) UC Ln UP /) ci - ) -C E B Ogilvie nd tkinson 1 11 pentgstrin cid output rtio ws -7 or greter. This figure ws tken to indicte tht the gstric vgl efferent supply ws intct. Six ptients fter truncl vgotomy were studied nd in ll the insulin/pentgstrin rtio ws less thn - nd this included two ptients in whom duodenl ulcertion hd recurred. Five of the proximl gstric vgotomy group hd rtios of less thn * nd the remining ptient gve vlue of -73. In Fig. the mximum chnge in lower *:* -1 _ -2 * _. -8 9,!Z -IC'< kc, C) ½>, Gut: first published s 1.113/gut on 1 Mrch Downloded from on 1 September 218 by guest. Protected by copyright.

5 Influence of the vgus nerve upon the reflex control of the lower oesophgel sphincter Fig. Reltionship between mximum chnge in lower oesophgel sphincter (LOS) pressure nd insulinl pentgstrin rtio. Controls re shown s, proximl gstric vgotomy s 1, truncl vgotomy without recurrent ulcertion s nd truncl vgotomy with recurrent ulcertion by e. Dotted lines represent lower limits ofnorml for both tests , 4 in 1,c O i -1-2 o -3 E : ~ oesophgel sphincter pressure with bdominl compression is plotted ginst the insulin/ pentgstrin rtio nd it will be seen tht there is no simple liner correltion between the two. In ll the control ptients both tests were norml nd it is of interest tht in the two ptients who developed recurrent duodenl ulcer fter truncl vgotomy the mximl chnge in lower oesophgel sphincter pressure ws within the norml rnge in spite of low insulin/pentgstrin rtio in contrst with the reminder of this group in which both tests were bnorml. In the proximl gstric vgotomy group there ws no correltion between the insulin/ pentgstrin rtio nd the mximl chnge in lower oesophgel sphincter pressure. Discussion Our finding tht the tone of the lower oesophgel sphincter normlly increses with increse in intrgstric pressure is in ccordnce with studies in which the sttion pull through technique ws used Others using the rpid pull through technique, however, hve filed to show such response1 11 nd the discrepncy my be explined by differences in the technique used. We took multiple mesurements of lower oesophgel sphincter pressure t ech cuff pressure, incresed the pressure in the cuff by smll increments nd plotted intrgstric pressure rther thn the pressure in the cuff itself ginst lower oesophgel sphincter pressure. The mrked response to smll chnges in intrgstric pressure nd the fct tht the response ws bolished by tropine suggests tht the pressure increse in the sphincter ws becuse of sphincteric ----I Insulin /pentgstrin PO rtio contrction nd not to externl mechnicl forces such s diphrgmtic contrction. Truncl vgotomy does not lter the resting lower oesophgel sphincter pressure12 13 nd our finding tht truncl vgotomy bolishes the response of the sphincter to incresed intrgstric pressure is in keeping with the work of others using the sttion pull through technique.3 4 The rise in lower oesophgel sphincter pressure fter crbchol, found in ptients with truncl vgotomy, indictes tht the smooth muscle of the sphincter is cpble of contrcting when stimulted directly but fils to do response to increse of intrgstric pressure suggesting interruption of the nervous pthwys which medite the sphincteric response. It is of interest tht in ptients studied fter truncl vgotomy the presence of recurrent duodenl ulcer correlted better with the sphincteric response to so in intr-bdominl compression thn it did with the insulin/pentgstrin gstric secretory rtio, suggesting tht the response of the lower oesophgel sphincter to bdominl compression might form vlid test for the completeness of surgicl vgotomy. Our findings support the view tht the response of the lower oesophgel sphincter to incresed intrbdominl pressure is medited by vgovgl reflex, the efferent limb of which includes muscrinic cholinergic pthwy blocked by tropine. The norml lower oesophgel sphincter pressure vlues found fter surgicl vgotomy suggest tht efferent vgl fibres to the lower oesophgel sphincter enter the oesophgus t higher level thn tht of vgl section t surgery nd rech the sphincter vi the oesophgel plexus. Interruption of fferent vgl fibres from the Il 27 Gut: first published s 1.113/gut on 1 Mrch Downloded from on 1 September 218 by guest. Protected by copyright.

6 28 Ogilvie nd tkinson bdomen, however, undoubtedly occurs t surgicl truncl vgotomy nd probbly ccounts for the lck of response of the- lower oesophgel sphincter to bdominl compression fter this procedure. Proximl gstric vgotomy in dogs does not bolish the sphincter response to bdominl compression14 but in our study only hlf of the ptients showed norml response. This my be due to vrible degree of interruption of fferent vgl fibres by proximl gstric vgotomy. s the response of the lower oesophgel sphincter to increse in intr-bdominl pressure is dependent on both intct fferent nd intct efferent vgl fibres we would suggest tht it is vlid test of vgl function in the upper limentry trct nd my be of use in the investigtion of utonomic neuropthy. References 1 Lind JF, Wrrin WG, Wnkling WJ. Responses of the gstro-oesophgel junction zone to increses in intrbdominl pressure. Cn J Surg 19; 9: Cohen S, Hrris LD. Does hitus herni ffect competence of the gstro-oesophgel sphincter? N Engl J Med 1971; 284: Crispin JS, McIver DK, Lind JF. Mnometric study of the effect of vgotomy on the gstro-oesophgel sphincter. Cn J Surg 197; 1: ngorn IB, Dimoupolos G, Hegrty MM, Moshl MG. The effect of vgotomy on the lower oesophgel sphincter: mnometric study. Br J Surg 1977; 4: 4-9. Csendes, Oster M, Brndsborg et l. The effect of vgotomy on humn gstro-oesophgel sphincter pressure in the resting stte nd following increses in intr-bdominl pressure. Surgery 1979; 8: Dodds WJ, Hogn WJ, Stef JJ, Miller WN, Lydon SB, rndorfer RC. rpid pull through technique for mesuring lower oesophgel pressure. Gstroenterolgy 197; 8: Hobsley M, Silen W. Use of n inert mrker (phenol red) to improve ccurcy in gstric secretion studies. Gut 199; 1: Fber RG, Russell RCG, Royston CMS, Whitfield P, Hobsley M. Duodenl reflux during insulin stimulted secretion. Gut 1974; 1: Venbles CW. The vlue of combined pentgstrin/ insulin test in studies of stoml ulcertion. Br J Surg 197; 7: Dodds WJ, Hogn WJ, Miller WN, Stef JJ, rndorfer RC, Lydon SB. Effect of incresed intr-bdominl pressure on lower oesophgel sphincter pressure. Dig Dis 197; 2: Greney MG, Irvin TT, Chttopdhyy DK. The mesurement of resting nd stimulted lower oesophgel sphincter pressure using the rpid pull through technique of oesophgel mnometry. Scnd J Gstroenterol 1978; 13: Mnn CV, Hrdcstle JD. The effect of vgotomy on the humn gstro-oesophgel sphincter. Gut 198; 9: Thoms P, Erlm RJ. The gstro-oesophgel junction before nd fter opertions for duodenl ulcer. Br J Surg 1973; : Khn T. Effect of proximl gstric vgotomy on the cnine lower oesophgel sphincter. m J Surg 1981; 141: Gut: first published s 1.113/gut on 1 Mrch Downloded from on 1 September 218 by guest. Protected by copyright.