Amelioration of Intestinal Dysmotility and Stasis by ...

Amelioration of Intestinal Dysmotility
and Stasis by Octreotide Early Mter
Small-Bowel Autotransplantation in Dogs

Koji Nakada, MD, Akira Ikoma, MD, Tomomi Suzuki, MD, James C. Reynolds, MD,
William L. Campbell, MD, Satoru Todo, MD, Thoma'> E. Starzl, MD, PhD, Pittsburgh, Pennsylvania

Reprinted from the March issue

The American Journal of Surgery

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SCIENTIFIC PAPERS

Amelioration of Intestinal Dysmotility
and Stasis by Octreotide Early Mter
Small-Bowel Autotransplantation in Dogs

Koji Nakada, MD, Akira Ikoma, MD, Tomomi Suzuki, MD, James C. Reynolds, MD,
William L. Campbell, MD, Satoru Todo, MD, Thomas E. Starzl, MD, PhD, Pittsburgh, Pennsylvania

BACKGROUND: Intestinal dysmotility and stasis af- secretions, and cell debris into the distal bowel,1O thereby
ter intestinal transplantation are considered to preventing intestinal stasis. Dysmotility and intestinal stasis
promote bacterial overgrowth and translocation. caused by disease!! or occurring after surgeryI2,13 have been
Two prokinetic agents, KW5139 (13-leu-motilin) shown to be ameliorated by motilin and somatostatin. In the
and the somatostatin analogue octreotide acetate, present study, the effects of KW5139, a synthetic 13-leu-
were studied to determine whether they can ame- motilin, and octreotide acetate, a somatostatin analogue, on
liorate intestinal dysmotility during the early post- impaired motility early after intestinal transplantation were
operative period. studied in dogs using an autotransplantation model.
Preliminary results were reported elsewhere. 14
MATERIALS AND METHODS: Motility was recorded by
multiple extraluminal strain-gauge transducers in 6 MATERIALS AND METHODS
dogs on postoperative days 1, 3, 7, and 14. A Animals
barium meal study was performed with a separate
group of 8 dogs on postoperative days 3 and 7. Six adult mongrel dogs of both sexes weighing 18 to 25
kg were used. They were given 1 g neomycin sulfate and
RESULTS: 'The agent KW5139 induced brief, 500 mg metronidazole per day and fed with a low-residue
weak contractions in the graft and had little effect diet for 5 days prior to surgery. Dogs were anesthetized with
on the dilated bowel; however, octreotide induced thiopental sodium (25 mglkg) for induction and maintained
motor activity that propelled accumulated intesti- with halothane, nitrous oxide, and oxygen by positive-pres-
nal contents into the colon and reduced dilation sure mechanical ventilation, Arterial blood pressure and
of the transplanted bowel. electrocardiograms were monitored.

CONCLUSION: Octreotide, but not KW5139, ame- Operative procedures
liorates intestinal dysmotility associated with bowel Autotransplantation Procedure. Operative procedures
autotransplantation during the early postoperative
period. Short-term administration of octreotide of canine intestinal autotransplantation were reported previ-
may be useful for the treatment of dysmotility fol- ously.IS In brief, through a midline incision, the small in-
lowing intestinal transplantation. testine from the ligament of Treitz to approximately 10 cm
from the ileocecal valve was isolated on a vascular pedicle
I t has been shown that motility of the intestinal graft is im- of the superior mesenteric artery and vein. After removing
paired after small-bowel transplantation. I,2 Dysmotility
during the early postoperative period is caused by muscular the intestine, the graft was perfused via the superior mesen-
and nervous damage secondary to intestinal transection, den- teric artery with I L cold lactated Ringer's solution con-
ervation, and ischemia. Dysmotility of the intestine causes
stasis of the intestinal contents, leading to bacterial over- taining 2,000 U heparin sodium and 0.3 mg kanamycin sul-
growth,3,4 which leads to bacterial translocation and sepsis. fate at 150 mm Hg. The intestinal lumen was irrigated with
Infectious complications are seen more frequently after in- 1 L of the same solution. After perfusion, the graft was im-
testinal transplantation5 than after transplantation of other mediately reimplanted into the same dog. The donor and na-
solid organs. Therefore, amelioration of intestinal dysmotil- tive superior mesenteric artery and vein were anastomosed
ity and stasis during the early posttransplant period appears in end-to-end fashion. Intestinal continuity was restored by
important to reduce the risk from these serious complications, end-to-end anastomosis of the jejunum and ileum,

Both motilin6 and somatostatin7-9 are known to induce Strain Gauge Transducer Placement. Eight strain gauge
phase 3 of the migrating motor complex. Phase 3 serves as transducers (Star Medical Co., Tokyo, Japan) were implanted
a "housekeeper" of the intestine by propelling food residue, before wound closure at the gastric antrum (5 cm proximal
to the pylorus), the pylorus, the duodenum (5 cm distal to the
From the Departments of Surgery (KN, AI, TS, ST, 1ES), Internal pylorus), the graft jejunum (15 cm and 45 cm distal to the
Medicine (JCR), and Radiology (WLC), Pittsburgh Transplantation duodenojejunal anastomosis), the graft ileum (40 cm and 10
Institute, University of Pittsburgh, School of Medicine, Pittsburgh, cm proximal to the ileoileal anastomosis), and the host ileum
Pennsylvania, (3 to 5 cm distal to the ileoilea1 anastomosis). Strain gauge
transducer lead wires were tunneled subcutaneously and
Supported in part by research grants from the Veterans Administration brought out between the scapulae. A protective jacket (Star
and Project Grant No, DK-29961 from the National Institutes of Health, Medical Co.) was placed on each dog to protect the lead wires.
Bethesda, Maryland.
Postoperative Management
Requests for reprints should be addressed to Thomas E. Starzl, MD, Animals received 1 L 5% dextrose in O.2N sodium chlo-
PhD, 5C Falk Clinic, 3601 Fifth Avenue, Pittsburgh, Pennsylvania 15213.
ride every 24 hours for 3 days postoperatively. One gram
Manuscript submitted September 3, 1993 and accepted in revised form
March 7, 1994.

294 THE AMERICAN JOURNAL OF SURGERY® VOLUME 169 MARCH 1995

_ _ _ _ _ _ _ _ _ _ _I__N__ TESTINAL DYSMOTILITY AFTER SMALL-BOWEL AUTOTRANSPLANTIONINAKADA ET AL

A.1 POD '4 B. 3 POD sent, the stomach was cleared by
flushing with water. After 6 to 8
Antrum ---- JJl uJi Ad j lit. 4 JL I hours of baseline recording, a 0.1-
I-Lg/kg intravenous bolus of syn-
Pylorus .~~ ....~"..J.4L.l'-L .'" , .I, ...- ....."'_•••• thesized leu-13-motilin (KW5139,
Kyowa HakIm, Tokyo, Japan)
Duodenum • A..! . ..I",", L ..... ' __ l Host was given. One hour after injec-
,.j.,j.. tion of KW5139, a 0.25-I-Lg/kg in-
... !l A A • travenous bolus of octreotide ac-
etate (Sandostatin, Sandoz, Basel,
Jejunum1 - - - - L - l I . • JJ ",'1 .l... " .•61.1 Switzerland) was injected, and
motor activity was followed for 1
Jejunum2 -'----... .....-.AL-..._-.Jl . 41'\"". ........,......... 10 • • additional hour. Both drugs were
.41 .. " given during a period of quies-
cence lasting at least 10 to 15 min-
.. j , ....-L .~-----~-~ ... . ... Graft utes after bursts of contraction
(BOCs) had ceased in the most
lIeum1 - .,. proximal portion of the autotrans-
lIeum2 j planted bowel. The dogs were
lIeum3 lI .-~- '" ... .... ~ trained to be quiet without restraint
-.L-Jl . ..... ..- I10ml" during recording. Motor activity
100; - I10min was recorded on a Gould TA4000
recorder (Gould, Inc., Cleveland,
.... ......Jl Ohio), and stored digitally.
........ .... ..JI"-,;, .,...,WO10'"0g Host
Radiological Observations
C.7POD D.14 POD Barium studies were perfom1ed

.'Al1I1.'"Antrum '.l!,H !~ J I.!I' ..... ........ -~. on a second group of 8 autotrans-
planted dogs on postoperative days
""~ i_ ! 3 and 7. Fifty milliliters of 45%
.. 1....& .J.. II...LI. .. 1111. ...&0 ..~ wtlvol barium sulfate suspension
i....... .......Pylorus lu. U• .1 w. Host without any nutrients was intro-
duced through an orogastric tube,
Duodenum .",...,... '-~ • .... • A.. ." .II .... followed 30 minutes later by a O.l-
I-Lg/kg intravenous bolus of
•.., J . ~.- hJJ,.~..La ~h ~..6J KW5139, and 60 minutes after that
by a 0.25-I-Lg/kg octreotide acetate
~j~1 • intravenous bolus. The fluoro-
Jejunum1 .1+1 1'\'..LJ,.. ..•••.\11 scopic images were observed on a
Jejunum2 • • •1" j ......... television monitor and stored on
videotape. Posteroanterior radio-
.lIeum1 ~l J~•-l- Graft graphs were obtained before and
15 and 30 minutes after introduc-
~ L . . *.lIeum2• ing the barium meal, and at 5, 15,
.... • .•l ...... ,A. • and 30 minutes after administra-
~ tion of each drug.
. ..... tll:lIeum3
I' -.... 10 min 1100 SI Jl __- •
~~ 10 min
. .... ....\ -L-.,.a. oo g

Host

Figure 1. Postoperative changes in interdigestive motility after smal~bowel autotransplantation in
the same dog: A. postoperative day 1; B. postoperative day 3; C. postoperative day 7; and D.
postoperative day 14. Incidence and duration of bursts of contractions (BOC) increased with time.
A dot signifies spontaneous phase 3 in the graft and an arrow indicates propagation of phase 3.

of cefamandol nafate was given intramuscularly during Data Analysis
surgery and then daily for 5 days. Dogs were allowed to The recorded motility of transplanted jejunoileum was vi-
drink and eat from the day after surgery. A meat-based,
low-residue liquid meal was given for the first 3 days af- sually analyzed. Phasic contractions lasting for a minimum
ter surgery, followed by a low-residue, solid-meat meal un- of 30 seconds with an amplitude of greater than 30 g and a
til postoperative day 7. Animals were fed standard kennel frequency of greater than 10 min-i were defmed as BOCs.
food thereafter. Spontaneous, strong, repetitive phasic contractions lasting
for more than 4 minutes and propagating aborally were de-
Motility Recordings fined as phase 3 contractions. Drug-induced strong, repeti-
Intestinal motility was recorded in fully conscious dogs tive phasic contractions lasting for longer than 2 minutes
were defined as phase-3-like contractions. The total dura-
on postoperative days l, 3, 7, and 14. Food was withdrawn tion of spontaneous contraction bursts (the sum of the du-
for 18 hours before each measurement. An orogastric tube ration of each burst), and the maximum duration and max-
was gently inserted to the stomach 6 to 8 hours prior to imum amplitude of spontaneous contractions from the last
each recording period, and if any residual food was pre- 3 hours of the baseline recording were compared with the

THE AMERICAN JOURNAL OF SURGERY® VOLUME 169 MARCH 1995 295

INTESTINAL DYSMOTlLlTY AFTER SMALL-BOWEL AUTOTRANSPLANTIONINAKADA ET AL

A t B t

60 60 POD 14
(min/3h) (minl3h)

U POD 1 POD 3 POD 7 POD 14 U
0
III 40 0m 40

'0 '0

II: II:
0
;:I =0

I! 20 I! 20

:::l :::J
Q
C
J0
i

t- O

POD 1 POD 3 POD 7

C t 0

() (g) POD 7 POD 14 u (9) t

0m 0 POD7 POD 14
ID

'0 200 '0 200

III a•.a'1:1
'1:1
:::J
~-a
E E
100 100
~ ~

E E
:::J
:::J
•-E;c
:-:E•;:ec 0
:::& 0

POD 1 POD3 POD 1 POD 3

Figure 2. Changes in total duration and maximum amplitude of bursts of contractions (BOC) after small-bowel transplantation: A. total duration
(jejunum); B. total duration (ileum); C. maximum amplitude (jejunum); and D. maximum amplitude (ileum). Total duration and maximum amplitude
of BOC significantly increased with time.• P <0.05 versus postoperative day 1. tP <0.05 versus postoperative day 3.

motility recordings after drug administration. The mean of TABLE
the five highest amplitudes of contraction bursts was de-
fined as the amplitude of BOCs. Appearance and Incidence of Phase 3 Activity
in the Transplanted Bowel
The incidence of phase 3 contractions was analyzed dur-
ing the entire baseline recording period. The type of oc- Appearance (nIN), Incidence (n/hlt
treotide-induced phase-3-like contractions was analyzed ac-
cording to the criteria described by Peeters et al,16 who POD Jejunum Ileum Jejunum Ileum
defined phase-3-like contractions seen either in jejunal or
ileal sites as "isolated" contractions, those propagating from 1 4/6 2/6 0.13±0.05l § 0.17±0.W
jejunum to ileum as "propagated" contractions, and those 3 5/6 5/6 0.44 ± 0.l6 0.23 ± 0.07
observed simultaneously in both the jejunum and the ileum 7 6/6 5/6 0.73 ± 0.05 0.52 ± 0.13
as "simultaneous" contractions. The maximum diameter of 14 6/6 5/6 0.70 ± 0.13 0.36 ± 0.l0
the bowel graft was measured in radiographs before and 30
minutes after octreotide injection. 'Number of dogs activity with phase 3 per number of experiments.

Statistical analysis was performed using the Wilcoxon's tNumber of phase 3 contractions per hour.
rank sum test. lP<O.05 compared with POD 7.

RESULTS §P<O.05 compared with POD 14.

All dogs survived the autotransplantation procedure. The POD; postoperative day.
dogs were healthy throughout the study period, and had a
good appetite. They lost 10.7% ± 1.3% of their weight dur- was occasionally interrupted by irregular weak and short
ing the first 2 weeks of the study. Watery diarrhea devel- contractions. Total duration and maximum amplitude of
oped 3 days after bowel transplantation and persisted BOCs were significantly less in the jejunum and ileum dur-
throughout the experimental period. ing this early period (Figure 2). After postoperative day 7,
however, intense and longer phasic contractions appeared
Motility Recordings in the intestine, and contractile activity became much more
Motility of the intestinal grafts was greatly inhibited for
evident (Figures Ie and D). Phase 3 activity was absent or
the first 3 days after autotransplantation (Figure 1). The
baseline recordings at postoperative day I (Figure lA) and occurred rarely in this early postoperative period (Table).
day 3 (Figure lB) showed long periods of quiescence, which The agent KW5139 always induced strong, repetitive pha-

sic contractions in the gastroduodenum from postoperative
day 1, but the contractions occurring in the graft were brief
and very irregular (Figure 3). No phase-3-like contractions
developed in the graft after KW5139 administration. Phase-
3-like contractions occurring in the native stomach and duo-
denum did not propagate into the graft beyond the proximal
intestinal anastomosis.

296 THE AMERICAN JOURNAL OF SURGERY· VOLUME 169 MARCH 1995

INTESTINAL DYSMOTILITY AFfER SMALL-BOWEL AUTOTRANSPLANTIONINAKADA ET AL

Antrum KW(O.1 ~g/kg) iv octreotide(O.25 Jlg/kg) Iv

.", .., +.'14 +-

Host

__Duodenum ~'~4.·'L-~"-·~~--~ ~.~!r"".~+~b~.~
____J~unum1 ~________~~I~aa- -
~-

Graft

Ileum 1 Figure 3. Motor activity induced by
KW5139 (KW) and octreotide in the
Ileum 2 ---.~--~---- transplanted bowel on postoperative day
Ileum 3 ~ ~)... .-J~_--'......._... _____"."... _ _ _ _ _ 1 in the same dog as in Figure 1.
. . ._ ..1,..0. ..m._in_11_0_09 Host KW5139 induced brief and weak irregu-
lar contractions, whereas octreotide in-
duced phase-3-like contractions simulta-
neously in the graft.

Octreotide always induced intense phase-3-like contrac- autotransplantation method was used in the experiment to
tions in the intestinal graft within 5 minutes after drug in- eliminate the influence of rejection and immunosuppressive
jection (Figure 3). Induction of these contractions was seen agents 17 on intestinal motility. We found that motility of the
on postoperative day 1, when motility was markedly im- intestinal grafts was severely impaired 3 days after trans-
paired. Simultaneous contractions (17 of 21) were predom- plantation and recovered after 7 days. Impairment of motil-
inant and occurred more often than isolated (4 of 21) or ity during the immediate postoperative period was charac-
propagated (0 of 21) contractions. In contrast to KW5139, terized by very little contractile activity and by intestinal
octreotide rarely produced phase-3-like contractions in the stasis. The agent KW5139 induced strong contractions in
host stomach (0 of 21) or duodenum (5 of 21). the gastroduodenum but had little effect on a dilated small
bowel. On the other hand, octreotide caused strong phase-
The duration and amplitude of KW5139-induced contrac- 3-like contractions in the jejunoileal graft even on postop-
tions were insignificant when compared with those of spon- erative day I, when motility was most abnormal. Vigorous
taneous BOCs (P <0.05), whereas octreotide-induced con- peristalsis occurred in the graft, and the accumulated in-
tractions were similar to those of the spontaneous bursts. testinal contents were emptied into the colon. Intestinal sta-
sis was virtually corrected by treatment with octreotide.
Radiologic Study
On postoperative day 3 (Figure 4A), the transplanted small In the fasting motor activity of a normal subject, the mi-
grating motor complex is classified into four separate phases
bowel and the host gastroduodenum were hypoperistaltic that propagate from the proximal gastrointestinal tract to the
and dilated when compared with radiological findings on distal intestine. Of the four phases,18 phase 3 is considered
postoperative day 7 (Figure 4B). When KW5139 was given, to have a distinctive role in the movement of intestinal con-
strong peristaltic contractions, lasting less than 10 minutes, tents by intense phasic contractions, or peristalsis, along the
occurred at the host stomach and duodenum, and emptied entire intestinal tract. After abdominal surgery, disappear-
the contrast material into the small bowel. However, ance of phase 3 contractions and resulting intestinal stasis
KW5139 had little effect on the dilated small bowel; only have been observed.12•19 The duration of the disappearance
weak and insignificant contractions were seen. In contrast, correlated with the severity of operative insults. After in-
octreotide induced strong and repetitive peristalsis through- testinal transplantation, reappearance of these contractions
out the entire intestine. However, this effect was not seen was greatly delayed. In rats, they reappeared after 11 days?
in the stomach. Fifteen minutes after octreotide injection, whereas it took 2 to 6 weeks in dogs.2o In the present study,
contrast material was propelled to the distal bowel, and the however, we found phase 3 contractions in the grafts, though
graft had cleared almost all the contrast material into the very rare, even on postoperative day 1 after autotransplan-
colon (Figure 4C). The maximum diameter of the dilated tation. Differences in species and monitoring methods may
small-bowel graft was 14.8 ± l.5 mm before octreotide in- have caused these disparities.
jection, and was significantly reduced to 6.8 ± l.5 mm 30
minutes after octreotide injection (P <0.05). Although both KW5139 and octreotide induce phase-3-
like contractions in the normal intestine,I 1-13 each drug's in-
COMMENTS fluence on the transplanted intestine was quite different.
In the present study, the effects of KW5139 and octreotide Whereas KW5139 showed little effect on contractile activ-
ity of the graft, octreotide induced vigorous contractions;
on dysmotility and stasis of the intestinal graft during the and KW5139 caused contractions in the gastroduodenum
early period after transplantation were studied in dogs. An

THE AMERICAN JOURNAL OF SURGERY'" VOLUME 169 MARCH 1995 297

INTESTINAL DYSMOTILITY AITER SMALL-BOWEL AUTOTRANSPLANTIONINAKADA ET AL

Figure 4. Radiological findings on days 3 and 7 following bowel trans-
plantation and effect of octreotide-induced motor activity on propu~
sion of intestinal contents on postoperative day 3. A. On postopera-
tive day 3, the transplanted jejunoileum was markedly dilated. B. On
postoperative day 7, dilation of the graft was reduced. C. On post-
operative day 3, 15 minutes after octreotide injection, octreotide-in-
duced motor activity propelled contrast material to the colon. The
graft bowel was emptied by this motility effect, which was accompa-
nied by a reduction in the dilation of the bowel.
but octreotide did not. It appears that KWSl39 and oc-
treotide exert their motor effects via different mechanisms.
It has been shown that atropine abolishes the prokinetic ef-
fect of these agents in the normal intestine,8.21 indicating that
cholinergic neurons are involved. There are two cholinergic
pathways in the gastrointestinal tract-Dne is via the ex-
trinsic nervous system and the other is via the intrinsic ner-
vous system. When hexamethonium is given22 or the intes-
tine is neurally isolated by denervation and transection,23
induction of phase-3-like activity by motilin, the mother
drug of KWS139, is lost. Therefore, KWSl39 appears to in-
duce phase-3-like contractions in the intestine through the
extrinsic nerve. In a segmental intra-arterial perfusion ex-
periment , Hostein et al9 demonstrated that somatostatin, the
mother drug of octreotide, induced contractile activity just
distal to the perfused segment, whereas systemic intravenous
administration caused no changes. Octreotide is thought to
induce motor activity in the intestine via a local mechanism.
The absence of a prokinetic effect on the stomach by so-
matostatin2-1 has been reported .

In the transplanted intestine, most of the phase-3-like con-
tractions induced by octreotide developed simultaneously,

298 THE AMERICAN JOURNAL OF SURGERY~ VOLUM E 169 MARCH 1995

_ _ _ _ _ _ _ _ _ _---OcIN:.cT_~_E_S"'T__=I"_'N"'AL~D"_'Y'_"S::c:Mco.:O"_'T=ILITY AFTER SMALL-BOWEL AUTOTRANSPL.\NTIONINAKADA ET AL

using the same dose that induced propagated contractions 8. Lux G, Femppel J. Lederer P, et al. Somatostatin induces interdi-
in the normal intestine.16 Since the extrinsic nerve has been gestive intestinal motor and secretory complex-like activity in man.
shown to modulate initiation or propagation, or both, of Gastroenterology. 1980;78: 1212. Abstract.
phase 3 contractions in the small boweJ,25 denervation may 9. Hostein J, Janssens J, Vantrappen G, et al. Somatostatin induces ec-
have influenced the pattern of phase-3-like contractions in topic activity fronts of the migrating motor complex via a local in-
the intestinal grafts. testinal mechanism. Gastroenterology. 1984;87: 1004-1008.
10. Szurszewski JH. A migrating electric complex of the canine small
To our knowledge, no radiological studies have previ- bowel. Am I Physiol. 1969;217:1757-1763.
ously been performed to study the effect of prokinetic 11. Soudah HC, Hasler WL, Owyang C. Effect of octreotide on in-
agents on intestinal dysr~otility following bowel trans- testinal motility and bacterial overgrowth in scleroderma. NElM.
plantation. By the third day after transplantation, intesti- 1991;325:1461-1467.
nal peristalsis was weak and hardly seen. The intestine was 12. Cullen JJ, Eagon lC, Dozois EJ, Kelly KA. Treatment of acute
markedly dilated, showing severe intestinal stasis. postoperative ileus with octreotide. Am I Surg. 1993;165: 113-120.
Octreotide, but not KW5139, ameliorated this stasis, pos- 13. Hanyu N, Ohira Y, Furukawa Y, et al. Effect of (leu 13)-motilin,
sibly by drug-induced phase-3-like contractions. In normal a motilin derivate, on GI motility in normal subjects. Gastroenterology.
dogs, the occurrence of peristalsis and the elimination of 1992;102:A494. Abstract.
contrast material were shown to coincide with the appear- 14. Nakada K, Ikoma A, Suzuki T, et al. Effect of octreotide on im-
ance of phase 3 contractions.3 paired intestinal motility in early period after small bowel auto trans-
plantation. Gastroenterology. 1993;104:A557. Abstract:
When intestinal stasis persists, it becomes a source of many 15. Yoshimi F, Nakamura K, Zhu Y, et al. Canine total small bowel
clinical problems. Intestinal stasis not only causes bacterial transplantation under FK506. Transplant Proc. 1991 ;23:3240-3242.
overgrowth and translocation, but also fluid and electrolyte 16. Peeters TL, Romanski W, Janssens J, Vantrappen G. Effect of
imbalance and microcirculatory disturbance of the intesti- long-acting somatostatin analogue SMS 201-995 on small-intestinal
nal wall, and may prolong recovery of patients after trans- interdigestive motility in the dog. Scand I Gastroenterol. 1988;23:
plantation. Therefore, it appears important to treat intestinal 769-774.
stasis to reduce these risks, esPecially during the immediate 17. Ikoma A, Nakada K, Suzuki T, et al. Effect of FK506 on gas-
postoperative period when the graft :suffers the most severe trointestinal tract: comparison with erythromycin. Gastroenterology.
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However, somatostatin also has deleterious effects, such as 21. Hall KE, Greenberg GR, EI-Sharkawy TY, Diamant NE.
gallstone formation,29 the inhibition of enterocyte prolifera- Relationship between porcine motilin-induced migrating motor com-
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avoided by limiting its use to a brief postoperative period. dogs. Gastroenterology. 1984;87:76-85.
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