ESOPHAGEAL MOTOR ABNORMALITIESINDUCED BY ACID PERFUSION IN PATIENTSWITH HEARTBURN

Charles I. Siegel, Thomas R. Hendrix

J Clin Invest. 1963;42(5):686-695. https://doi.org/10.1172/JCI104760.

Research Article

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Journal of Clinical InvestigationVol. 42, No. 5, 1963

ESOPHAGEALMOTORABNORMALITIES INDUCED BY ACIDPERFUSION IN PATIENTS WITH HEARTBURN*

By CHARLESI. SIEGEL AND THOMASR. HENDRIXt

(From the Department of Medicine, The Johns Hopkins University School of Medicine,Baltimore, Md.)

(Submitted for publication July 2, 1962; accepted January 24, 1963)

The clinical diagnosis of esophagitis is sug-gested by the presence of severe heartburn whichis aggravated by the recumbent position. Thesymptom is generally worse after eating and isrelieved by antacids. It is generally held that in-creased reflux of gastric contents leads to the de-velopment of esophagitis and that the pain is as-sociated with an inflammatory process. In manypatients with symptoms that suggest a diagnosis ofesophagitis, however, there is, no endoscopic orhistologic evidence of inflammation. The poorcorrelation between the clinical diagnosis of esopha-gitis and the endoscopic and histologic observa-tions led to an investigation of esophageal motorfunction in these patients.

METHODAND MATERIALS

Twenty-five patients with the clinical diagnosis ofesophagitis were studied. The clinical diagnosis wasbased on the following criteria: recurrent burning retro-sternal pain, which was more severe after eating, ag-gravated by the recumbent position, and improved byantacids. Esophagoscopy was performed in all patients.Specific features noted were mucosal reddening, granu-larity, erosion, ulceration, stricture, and the presence anddegree of gastroesophageal reflux. Esophageal biopsieswere obtained from an involved area if gross changeswere observed and from the distal 4 cm of esophaguswhen no endoscopic abnormalities were present. X raysof the upper gastrointestinal tract with special attentionto the gastroesophageal junction were obtained in allpatients. Radiographic evidence of hiatus hernia andesophageal reflux was sought with the patients in theTrendelenburg position. Acid perfusion of the loweresophagus, with the technique to be described, was per-formed on all patients.

These patients were compared with a control group of25 patients who had none of the criteria described abovefor the clinical diagnosis of esophagitis. The controlgroup, some of whom had coronary artery disease, were

*This investigation was supported by U. S. PublicHealth Service research grant A-1687(C4) and U. S.Public Health Service training grant 2A-5095(C4).

t John and Mary R. Markle Scholar.

not all esophagoscoped, but acid-perfusion studies andradiologic studies were performed in all. A tabulateddescription of the heartburn and the control groups isfound in Tables I and II.

Pathologic findings and motility records were gradedwithout knowledge of the clinical or endoscopic findings.On the other hand, the esophagoscopist was usually underthe impression that the clinical diagnosis was esophagitis.

Esophageal motor studies were performed with thesubj ect supine. Three open-tipped, water-filled poly-vinyl catheters with the tips placed 5 cm apart were in-troduced into the stomach. The catheters were con-nected to external transducers that were leveled at theposterior axillary line, and simultaneous, four-channel,direct-writing recording was performed.' The cathe-ters were withdrawn into the esophagus in 1-cm steps tomeasure the resting tone of the lower esophageal sphincter.After the resting pressure of the lower esophagealsphincter and the motor response of the lower esopha-gus to swallowing were recorded, the distal tip was with-drawn to a position 5 cm above the lower esophagealsphincter. The acid-perfusion studies were then per-formed as indicated schematically in Figure 1. Continu-ous perfusion of the esophagus was performed throughthe proximal catheter for three test periods, first withisotonic saline, second with 0.1 N HCl, and third withsaline. Motor recording was performed through themiddle and distal catheter tips. Catheters were flushedonly if dampening of excursions appeared. The perfu-sion periods with saline were 10 minutes long, and theperfusion with, 0.1 N HCl was continued for 20 minutes,or less if the patient's symptoms were exactly duplicatedafter a shorter interval of acid perfusion. The rate ofperfusion was 90 to 120 drops per minute, and at thisrate secondary peristalsis was only rarely initiated. Theinitiation of perfusion and the change from one solutionto another were performed so that the patient was un-aware of these maneuvers. Spontaneous motor activityas well as the response to "dry" swallows (the bolusconsisting of the patient's saliva rather than a sip ofwater) were monitored continuously throughout all testperiods. The specific intent was to determine whetheracid-induced heartburn was associated with motor ab-normalities of the lower esophagus.

1 Sanborn differential pressure transducers, model 267B, were employed in these studies. The recordings weremade with a Sanborn four-channel, direct-writing re-corder.

686

ACID-INDUCED ESOPHAGEALMOTORABNORMALITIES

TABLE I

Heartburn group

Effective lowerX ray esophageal

sphincter ResponseHiatus Peptic Esophagos- Esophageal mean resting to acid

Patient Age Sex hernia ulcer copy* biopsyt pressure perfusiont

mmHgA.P. 49 M + 1+ N 1 3+E.C. 54 F + 1+ N 2 3+F.L. 32 F 0 N 2 3+A.R. 39 M + + 2+ I 2 3+E.T. 45 M 0 I 1 3+B.U. 41 F 1+ I 2.5 2+N.L. 44 F 0 I 1 3+M.T. 45 F 2+ I 2 3+A.Z. 36 M + 2+ N 3 2+J.K. 59 F + 1+ I 2 2+A.L. 46 F 2+ I 9 2+L.H. 60 F 2+ I 2 2+L.R. 56 M 2+ I 2.7 3+I.K. 47 F + 2+ I 3 3+H.H. 56 F 0 I 0.3 2+H.R. 48 M 1+ I 2 3+J.N. 19 M + 2+ N 1.3 3+B.W. 68 F 1+ I 1 3+L.G. 50 F + 1+ I 1.1 3+E.W. 41 F 2+ I 2 2+L.F. 52 F + 0 N 1 3+C.C. 48 F + 1+ I . 0.7 3 +E.l. 46 F + 2+ I 1.6 2+J.O. 70 M + 2+ I 1 2+L.T. 53 F + + 2+ N 2.7 2+

Total 11 4 0= 5 I 1= 8 Mean 2.01+ =8 N= 72+ = 12

* 0 = no abnormality; 1 + = reddening of the mucost; and 2 + = granularity or friability of the mucosa, or both.t I = inflammation, N=normal.T 3 + = duplication of the patient's symptoms; 2+ = symptoms qualitatively similar but less severe; and 1+

= symptoms unlike the patient's spontaneous symptoms.

0.1 N HCL

SALI NE

_____ _ _ _ _ _ _ _ _ _ _ _ _ _ --_

__ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 5~~~~~~

I__

40

mm. 30 rHg 20

40 Lmm. 30

Hg 20

0 1 2010

TIME IN SECONDS

FIG. 1. SCHEMATIC REPRESENTATIONOF TECHNIQUE OF ACID PERFUSION.The uppermost catheter is employed for perfusion. By a threeway stop-cock, the perfusing solution may be changed without knowledge of the pa-tient. Continuous, simultaneous recording is performed through the twodistal catheters.

687

CHARLESI. SIEGEL AND THOMASR. HENDRIX

-

A

AV A;N- .4

FIG. 2. THREEBIOPSIES OF THE LOWERESOPHAGUS. A. The biopsy wasobtained from a patient who was symptom free at the time of and for sev-eral months before biopsy. This biopsy shows severe changes consisting ofnecrosis of the epithelium with pseudomembrane formation and severe sub-acute and chronic inflammatory changes in the submucosa. B. The biopsywas obtained from a patient with moderate symptoms. The changes ob-served in this biopsy consist of a moderately increased vascularity of the epi-thelium and the lamina propria with a minimal increase in mononuclear cells.C. The biopsy was obtained from a patient who was disabled by severe symp-toms. Her biopsy was virtually normal. This lack of correlation betweenhistologic abnormality and the occurrence of symptoms was frequently en-countered as described in the text and summarized in Table III. Magnifi-cation 100 x.

688

ACID-INDUCED ESOPHAGEALMOTORABNORMALITIES

1: i.1 I

..i '.. ...,....r1:.;.5 :.

.." i Is0- W-,AALIZ= .1FIG. 2-(Continited)

TABLE II

Control group

Effective lowerX ray esophageal

sphincter ResponseHiatus Peptic Esoph- Esophageal mean resting to acid

Patient Age Sex hernia ulcer agoscopy* biopsyt pressure perfusiont

mmHgR.W. 41 F 0 7 0A.B. 51 F 0 N 3.3 0J.B. 62 M 0 N 2 0B.G. 37 F 0 N 7.7 0R.B. 69 F + 6.3 0E.H. 44 F 0 N 9 0N.J. 46 M + 7.7 0R.S. 67 F + 3.5 0L.S. 52 F + 2 + I 2 0W.S. 44 MI 6 0H.D. 48 M 1+ 2 0L.S. 50 F 2+ N 3.7 0R.G. 35 F 1.8 0A.F. 64 XI 5.8 0P.S. 43 Mi + + 1.6 0XV.S. 45 M 6.8 0E.L. 45 M 5.5 0M.R. 51 F 6 0E.W. 61 F 1+ I 6 0M.H. 63 F 6.5 0W.S. 52 MI 6 0L.B. 70 M 6 0E.T. 55 F 5.5 0J.C. 33 F 7.6 0J.W!. 32 MI 1 + I 3 0

Total 4 2 0 =5 I =3 Mean 5.11+ =3 N= 52+ = 2

* 0 = no abnormality; 1+ = reddening of the mucosa; and 2 + = granularity or friability of the mucosa, or both.t I = Inflammation, N=normal.t 3+ = duplication of the patient's symptoms; 2+ = symptoms qualitatively similar but less severe; and 1+

= symptoms unlike the patient's spontaneous symptoms, O=no response.

689

CHARLESI. SIEGEL AND THOMASR. HENDRIX

TABLE III

Histologic and acid-perfusion data inheartburn and control groups

Number Positive Biopsyof acid

Group patients perfusion Esophagitis Normal

Heartburn 25 25 18 7Control 25 0 3 5

RESULTS

Correlation of esophageal symptoms wuith gross

and histologic evidence of inflammation. Grossand histologic evidence of esophageal inflammationdid not correlate either by its presence or inten-sity with the symptoms of heartburn. Severalbiopsies with the most severe inflammatorychanges were obtained from patients who were

asymptomatic. Conversely, patients with severe

symptoms occasionally had normal biopsies. Threebiopsies where symptoms actually bore an in-verse relationship to severity of inflammatorychanges are shown in Figure 2. Of the group of25 patients with heartburn of such severity that

7*

5

MEANRESTING 4,

PRESSUREmmHg S

ABOVE 3 .MEAN

INTRAGASTRIC0

PRESSURE . .__,, . .

Heartburn ControlsFIG. 3. EFFECTIVE RESTING PRESSURE IN THE LOWER

ESOPHAGEALSPHINCTER (MEAN RESTING INTRASPHINCTERIC

PRESSURE MINUS MEAN INTRAGASTRIC PRESSURE) IS

PLOTTED FOR THE HEARTBURNPATIENTS AND FOR THE

CONTROLGROUP. Twenty-four of 25 patients in the heart-burn group had sphincteric pressure of 3 mmHg or lessin excess of intragastric pressure. In 19 of the 25 mem-

bers of the control group, this value was in excess of 3mmHg. The mean for each group is plotted by a

transverse line.

it was ascribed to esophagitis, 18 had esophagealbiopsies showing inflammatory changes, whileseven had normal biopsies. From Tables I andII it can be seen that the esophagoscopic evalua-tion of mucosal inflammation does not closelyparallel the actual histologic findings. Clinically,the patients with histologic evidence of inflam-mation could not be differentiated from those withnormal findings. Ten of the 25 patients in thecontrol group were esophagoscoped. Five of theten showed reddening of the esophageal mucosa,

and in two patients, this was accompanied by gran-

ularity of the mucosa. Three of the patients show-ing endoscopic abnormalities had mild to moderatechronic inflammatory changes on biopsy. None ofthese patients had heartburn or other symptomsof esophagitis (Table III).

TABLE IV

Acid-induced esophageal motor abnormalitiesin heartburn and control groups

TotalIn- acid-

Num- Syn- creased Pro- inducedber chro- intra- longed motorof nous luminal peri- abnor-

Group patients activity pressure stalsis malities

Heartburn 25 23 24 24 25Control 25 2 0 2 2*

* Four control patients had isolated motor abnormalities. In twopatients, these were seen only in the acid-perfusion period. In theother two, the abnormalities appeared sporadically in both saline andacid-perfusion periods.

Correlation of esophageal symptoms with rest-ing pressure in the lower esophageal sphincter.The resting pressure of the lower esophagealsphincter was measured at least three times ineach of the patients and controls by withdrawingthe three catheter tips through the area of thesphincter in 1-cm steps. The resting pressurerecorded at each level was the average of the end-inspiratory and end-expiratory pressures. Themean resting pressure of the lower esophagealsphincter was obtained by averaging all technicallysatisfactory runs. The mean intrasphinctericpressure exceeded mean intragastric pressure bymore than 3 mmHg in only one of the 25 pa-tients with esophageal symptoms, whereas the dif-ference was greater than 3 mmHg in 19 of- the25 controls (Figure 3).

Correlation of symptoms with results of acid-perfusion study and description of motor ab-normalities observed. In all 25 patients with

690

I

ACID-INDUCED ESOPHAGEALMOTORABNORMALITIES

0.1 N HC.LPAIN

40 I'ITI2FTs]-F;Xl30mm. gt|-I U8tzt- f

H9 20.. ....l .g

' '**L ; :;C:I;......... ':.7. :.....

...S..~q

40

mm. X _Hn20 _ =Hg;l;l t'ze1-nns-

- I 0 't'I-}XE-Esi .la0r m _

60-60 0 20 40 60

TIME IN SECONDSFIG. 4. RECORDINGSOF ESOPHAGEALPERISTALSIS ARE SHOWNDURING THE

PAIN-FREE, SALINE-PERFUSION PERIOD AND DURING ACID-INDUCED PAIN. Com-parison of the records demonstrates a marked increase in amplitude andduration of peristaltic contraction during the symptomatic period.

heartburn, spontaneously occurring symptomswere produced by acid perfusion, but not by sa-

line. Symptoms were produced in none of thecontrols. In all cases where esophageal symptomswere induced, motor abnormalities were observedin the lower esophagus (Table IV). These con-

sisted of three types. The first type of motor ab-normality observed was increased amplitude andduration of peristaltic contractions (Figure 4).During the period of acid perfusion when the pa-

tients experienced pain and heartburn, the ampli-tude and duration of peristaltic contractions in-creased to as much as twice that observed in thepain-free period. These motor changes occurredin 24 of the 25 patients with heartburn. The sec-

ond type observed consisted of nonprogressiveesophageal contractions which were spontaneousand did not occur in response to a swallow (Fig-ure 5 ). Such contractions, occurring at twopoints 5 cm apart at exactly the same time, repre-

sented spastic, nonperistaltic contractions. Thesewere associated with an increased severity ofsymptoms. This motor abnormality occurred in23 of the 25 patients. The third motor abnor-mality was increased esophageal tone as mani-fested by a gradual increase in intraluminal pres-

sure (Figure 6). This was observed in 25 of the25 patients.

mmHg

mmHg

30 -

20 -

I O -.0-I0 -

20 -2I f-

I u

0

+ 4 +

r

t.1:

4-

1:r

FI

,;,,..j ..1 ,.,, § ~... ... ....-t:1'' t .- .' '. *t 4....... ........-..

.... .... ... z. .,+ .. s...s* ~~~~~~~~~~~~~~~. ....... ._._.j..v4 <v ... ... .*.... .. . ...~ ... ...r -* ....., +.+ _.

..._... .... *f ..... ..*F + t<.,.*+ + .... .... .....*--''+''''-- sw ... +n .. -~F ns-*. ---*.... .... .... . ..t ~~~~~~~~~~~~~~~~~~. .. _,z-.'_".;'.'..... t.. i. .8. _._. ... ....1 8... ....... . .... .,... .... *.-,.

..... .... .... .144.._. .. .+** .. . . .... ., ..~~~~~~~~~~~~~~~~~~~~~~~~~~. * *-...... _e..

.. . 1. _, _-'p_...'-U; _....

.... .... ....* .-. .**

..........tt d - e*s t'It ''e*--t* .... .... .... *'''-~~~~~~~~~~~~~~~... .. .... ....*-*.

0 10 20 30 40 50 60 70 80

TIME IN SECONDS

FIG. 5. NONPROGRESSIVE ESOPHAGEAL CONTRACTIONS(INDICATED BY ARROWS) OCCURREDDURING PERIODS OFACID-INDUCED SYMPTOMSIN 23 OF THE 25 PATIENTS.These nonperistaltic contractions occurred without ante-cedent swallows and represented localized or segmentalcontractions.

SALI NE

NO PAIN40 r

mm. 30

Hg 2010 -

0 L

40r30

mm.20Hg 00

0 20 40

-

691

CHARLESI. SIEGEL AND THOMASR. HENDRIX

SALINE 0.1 N. HCINO PAIN PAIN

30+/

1021| -

)%ttN'S))$';.

....

...... ..

.........

...I .. ..

, T . .

O 20 40

mmHg

30E

20

10

0

30,

mm 20Hg 10

0

.-

rgf.

.~ ~~~~~~~~~~~.........

v

0 20 40 60

TIME IN SECONDSFIG. 6. INCREASED ESOPHAGEALTONE DURING ACID-INDUCED PAIN. During

saline perfusion, no pain was experienced and the intraluminal pressure re-

mained at a constant level. With acid-induced symptoms, intraluminal pres-sure gradually rose, so that without either peristaltic or nonprogressive con-

traction, an elevated resting pressure was maintained. In the absence of othermotor activity, this change may reasonably be assumed to reflect a rise in toneof the esophageal wall.

(RECORDING TIPS 5cm. APART)

SALINE 0.1 N HCLNO PAIN PAI N

40 i ~~~~~~~~~~40r

ME. .7!.2 - °LI~ ~ ~ ~ ~ ~ ~ ~ ~~7

40 rHMa 30MM

0 20

At I- -

0 30 40 60 10

TIME IN SECONDS

I I I

IL !

0 to 40 so so 100 180' 140 160 ISO

TIME IN SECONDSFIG. 7. A CHARACTERISTIC MOTORRECORDINGFROMA POSITIVE ACID-PERFUSION TEST. During the pain-free, saline-

perfusion period (on the left), there is no motor activity other than that initiated by swallows (indicated by arrows).

The recording on the right, from the acid-perfusion period with induced pain, shows all three types of motor abnor-

malities described.

692

mm

Hoo4

30~mm 20Hg 10

0.

I-

I I f

ACID-INNDUCED ESOPHAGEALMOTORABNORNMIALITIES

Motor abnormalities of one or more of the typesdescribed above were observed in four of the 25controls. These motor abnormalities were not as-sociated with symptoms. In two subjects, motorabnormalities were present during the saline aswell as the acid-perfusion periods, and thus, nottruly acid induced. They occurred as sporadicmotor abnormalities in contrast to the sustainedmotor activity observed during the symptomaticperiods in the heartburn group.

A characteristic motor recording obtained froma patient with acid-induced pain is shown in Fig-ure 7. During the pain-free saline perfusion, mo-tor activity appeared in the esophagus only in re-sponse to swallows, and each response was peri-staltic. During the period of acid-induced pain, onthe other hand, a great deal of spontaneous motoractivity was observed unrelated to swallowing.-Much of this spontaneous motor activity was notperistaltic.

The extent of the motor abnormalities paralleledthe severity of the symptoms. In a number of thepatients motor abnormalities were present beforethe patient volunteered that symptoms had de-veloped. As the motor abnormalities grew moremarked, symptoms appeared as though a thresholdhad been exceeded.

DISCUSSION

It is generally accepted that reflux of gastricjuice into the lower esophagus plays a role in thepathogenesis of esophagitis. This has focused at-tention on the nature of the mechanism that nor-mally prevents gastroesophageal reflux. Threemechanism are postulated (1, 2): one entails theexistence of a "flap-valve" at the gastroesophagealjunction (3); a second mechanism postulates a"pinchcock" action on the right crus of the dia-phragm (4) ; and the third stresses the primaryrole of the intrinsic sphincter in the lower esopha-gus (5-8). Although the anatomic demonstra-tion of a sphincter in this location is not readilyperformed, manometric data have clearly demon-strated a zone that maintains an elevated restingpressure and relaxes as the peristaltic wave ap-proaches (9). The evidence for the lower eso-phageal sphincter being the principal barrier toreflux is considerable (10-12). Experimentalsurgical studies have shown that displacement of

the gastroesophageal junction to above or belowthe level of the hiatus of the diaphragm will not, byitself, promote reflux. However, the excision ofthe "vestibule," the zone in which the sphincter islocated, will regularly lead to severe esophagitis.In patients with hiatus hernia, Atkinson, Edwards,Honour, and Rowlands (13) have shown that theoccurrence of symptoms correlates very closelywith the amplitude of the resting pressure of thelower esophageal sphincter. Those patients witha hiatus hernia who had a normal lower esophag-eal sphincter were free of symptoms despite theabnormal location of the gastroesophageal junc-tion. Among the patients in our series both withand without hiatus hernia, the correlation of oc-currence of symptoms and a diminished restingpressure of the lower esophageal sphincter is aclose one (Figure 3). In 96% of patients withfrequent and persistent burning retrosternal pain.a mean intrasphincteric pressure of only 3 mmHgor less was found. In 767% of patients withoutreflux symptoms, the intrasphincteric pressure wasgreater than 3 mm Hg. The available datastrongly support the premise that the lower eso-phageal sphincter constitutes the principal barrierto reflux, but the role of other factors, such as theintegrity of the phrenicoesophageal ligament, re-quires further study.

Bernstein and associates (14, 15) and Tuttle,Bettarello, and Grossman (16) proposed acid per-fusion of the esophagus as an objective test for thelocalization of the origin of chest pain. Repro-duction of the patient's symptoms with acid per-fusion constituted evidence for the esophagealorigin of these symptoms. An inflammatoryprocess has been suggested as the basis of thesymptoms of these patients. In those cases whereendoscopic changes were not found, it was reasonedthat microscopic inflammatory changes were pres-ent (14). However, upon obtaining esophagealbiopsies in our 25 patients with heartburn andtypical clinical features of esophagitis, no histo-logic evidence of inflammation was found in biop-sies from seven patients. Conversely, of eightpatients in the asymptomatic control group fromwhombiopsies were taken, three showed histologicevidence of chronic inflammation. The poor cor-relation between the presence of inflammation andthe occurrence of symptoms renders improbablethe idea that an inflammatory process is essential

693

CHARLESI. SIEGEL AND THOMASR. HENDRIX

for the mediation of symptoms attributed toesophagitis.

Acid perfusion of the lower esophagus in pa-tients with severe and persistent heartburn con-sistently reproduces their symptoms. In our ex-perience, these induced symptoms have uniformlybeen accompanied by motor abnormalities. Con-versely, regardless of the presence or absence ofhistologic evidence of inflammation, patients with-out esophageal symptoms have not experiencedsymptoms in response to 0.1 N HCl perfusion.Four patients in the control group had minor mo-tor abnormalities during acid perfusion, but thesewere not associated with symptoms and occurredwith equal frequency and magnitude in the sa-line-perfusion periods. Thus the symptom ofheartburn correlates more closely with acid-inducedpain and motor abnormalities than with X-ray,endoscopic, or histologic abnormalities.

Three types of motor abnormalities were in-duced by acid perfusion in patients with heartburn(Table IV). These acid-induced motor abnor-malities were associated with either a transient ora prolonged aggravation of burning pain, an asso-ciation that further enhances the likely role of mo-tor abnormalities in the mediation of these symp-toms. This view, which is contrary to most re-cent thinking, was advanced by Jones (17) manyyears ago. He induced heartburn by rapid dis-tention of the lower esophagus. His fluoroscopicobservations revealed motor abnormalities of thelower esophagus that he interpreted as reverseperistalsis, but were, in all likelihood, producedby nonprogressive contractions of the distal esoph-agus. Several observers, on the other hand, havenot found motor abnormalities in association withreflux symptoms, but these negative observationsmay be accounted for in part by differences intechnique, such as the use of the upright positionand higher rates of perfusion (18). Nagler andSpiro (19) in their study of heartburn of preg-nancy minimized the role of motor abnormalitiesin the genesis of heartburn. It should be noted,however, that they demonstrated motor abnor-malities in all three patients who had heartburnduring their manometric studies. In one of theirillustrations, esophageal motor abnormalities dis-appeared at the time heartburn ceased.

Perfusion of 0.1 N HCl is a convenient and re-

producible way of mimicking reflux. However,hydrochloric acid is not necessarily the sole nox-ious substance in gastric secretions; indeed, erosiveesophagitis has been described in patients withachlorhydria (20).

The formulation of the basis for the symptomsof heartburn entails two factors. The first is re-flux of an irritating material facilitated by de-creased tone of the lower esophageal sphincter.The second is the reactivity of the distal esophagusto the refluxed material, which is manifested bymotor abnormalities. Further. the reactivity ofthe distal esophagus may vary in a given individualboth in response to therapy and to other unknownfactors, accounting for the intermittent characterof these symptoms. As indicated above, symptomsmay occur in the absence of inflammatory changes,and marked inflammation may be present withoutsymptoms. Thus reflux of a noxious material intothe esophagus and increased reactivity of the dis-tal esophagus to such material, rather than inflam-mation, are the basic factors in the development ofheartburn.

SUMMARY

A study was performed correlating clinical,endoscopic, histologic, and acid-perfusion studieswith intraluminal manometric recording in 25 pa-tients with heartburn who, from their histories,were thought to have esophagitis. Histologic evi-dence of inflammation was found in only 18 of the25. These patients were compared with a groupof 25 patients with no esophageal symptoms.Acid perfusion produced substernal pain in all thepatients in the heartburn group but in none of thecontrols. Motor abnormalities were observed inall patients in whom acid perfusion reproducedsymptoms, suggesting that disordered motor func-tion plays a role in the production of these esophag-eal symptoms. From these studies it is evidentthat the symptom of heartburn correlates moreclosely with reactivity of the esophagus to per-fused acid than to the presence of inflammation.The common denominator in these patients is anesophagus which, due to an as yet unknown mech-anism, is unduly reactive to refluxed gastric con-tents. This abnormal reactivity is manifested byheartburn and concomitant esophageal motor ab-normalities.

694

ACID-INDUCED ESOPHAGEALMOTORABNORMALITIES

REFERENCES

1. Ingelfinger, F. J. Esophageal motility. Physiol.Rev. 1958, 38, 533.

2. Botha, G. S. M. Mucosal folds at the cardia as a

component of the gastrocesophageal closing mecha-nism. Brit. J. Surg. 1958, 45, 569.

3. Von Gubaroff, A. fber den Verschluss der men-

schlichen Magens an der Cardia. Arch. Anat.Entwickl.-Gesch. 1886, 395.

4. Jackson, C. The diaphragmatic pinchcock in so-called"cardiospasm." Laryngoscope (St. Louis) 1922,32, 139.

5. Fleshler, B., T. R. Hendrix, P. Kramer, and F. J.Ingelfinger. Resistance and reflex function of thelower esophageal sphincter. J. appl. Physiol. 1958,12, 339.

6. Fyke, F. E., Jr., C. F. Code, and J. F. Schlegel. Thegastroesophageal sphincter in healthy human beings.Gastroenterologia (Basel) 1956, 86, 135.

7. Pert, J. H., M. Davidson, T. P. Almy, and M. H.Sleisenger. Esophageal catheterization studies.I. The mechanism of swallowing in normal sub-jects with particular reference to the vestibule(esophago-gastric sphincter). J. clin. Invest. 1959,38, 397.

8. Vantrappen, G., E. C. Texter, Jr., C. J. Barborka, andJ. Vandenbroucke. The closing mechanism at thegastroesophageal junction. Amer. J. Med. 1960,28, 564.

9. Atkinson, M., D. A. W. Edwards, J. A. Honour, andE. N. Rowlands. Comparison of cardiac and py-

loric sphincters. A manometric study. Lancet1957, 2, 918.

10. Ingram, P. R., J. C. Respess, and WV. H. Muller, Jr.The role of an intrinsic sphincter mechanism inthe prevention of reflux esophagitis. Surg. Gynec.Obstet. 1959, 109, 659.

11. Braasch, J. W., and F. H. Ellis, Jr. The gastro-esophageal sphincter mechanism: an experimentalstudy. Surgery 1956, 39, 901.

12. Ingram, P. R., R. K. Keswani, and W. H. Muller,Jr. A correlative histopathologic study of ex-

perimental surgical reflux esophagitis. Surg.Gynec. Obstet. 1960, 111, 403.

13. Atkinson, M., D. A. W. Edwards, A. J. Honour, andE. N. Rowlands. The cesophagogastric sphincter inhiatus hernia. Lancet 1957, 2, 1138.

14. Bernstein, L. M., and L. A. Baker. A clinical testfor esophagitis. Gastroenterology 1958, 34, 760.

15. Bernstein, L. M., R. Pacini, R. C. Fruin, and E.Gorrett. Esophagitis as a cause of upper abdomi-nal pain. J. Amer. Med. Ass. 1958, 168, 27.

16. Tuttle, S. G., A. Bettarello, and M. I. Grossman.Esophageal acid perfusion test and a gastroesopha-geal reflux test in patients with esophagitis. Gas-troenterology 1960, 38, 861.

17. Jones, C. M. Digestive Tract Pain. New York,Macmillan, 1938.

18. Tuttle, S. G., F. Rufin, and A. Bettarello. The physi-ology of heartburn. Ann. intern. Med. 1961, 55,292.

19. Nagler, R., and H. M. Spiro. Heartburn in latepregnancy. Manometric studies of esophageal mo-

tor function. J. clin. Invest. 1961, 40, 954.20. Palmer, E. D. Subacute erosive ("peptic") esopha-

gitis associated with achlorhydria. New Eng. J.Med. 1960, 262, 927.

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