Improvement of intestinal motility using S-methylisothiourea in
Shouiti Uenoyama, M.D.
*, Toshihiko Kobayashi, M.D.
, Yutaka Takeuchi, M.D., Ph.D.
Kimihiro Yamashita, M.D.
, Yukio Koide, M.D.
, Teruhisa Kazui, M.D.
First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Japan 431-3192
Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Manuscript received June 17, 2002; revised manuscript October 28, 2002
Background: The inﬂammatory mediator nitric oxide (NO) plays an important role in postoperative gastrointestinal motility.
Methods: Using S-methylisothiourea sulfate (SMT), a selective inducible nitric oxide synthase inhibitor, we studied the physiological role
of the endogenous NO in the modulation of intestinal motility. The study was performed in vivo in a canine postoperative model. Ten
mongrel dogs were treated with a continuous intravenous infusion of SMT after a surgical intestinal manipulation. Small intestine transit
time was ﬂuoroscopically measured using barium sulfate as it passed through a gastrostomy tube on postoperative days (POD) 1, 2, and 3.
Results: Average transit times on POD 1 in the 4 mg/kg/h and 2 mg/kg/h SMT groups signiﬁcantly decreased compared with that of the
saline group. However, the transit times on POD 2 and 3 were not signiﬁcantly different among the three groups.
Conclusions: S-methylisothiourea sulfate improves small intestine motility at an early postoperative stage. © 2004 Excerpta Medica, Inc.
All rights reserved.
Keywords: Motility; Ileus; Isothiourea; Nitric oxide; Dog
Dysmotility of the intestine related to postoperative ileus is
one of the common complications of gastrointestinal sur-
gery. A number of explanations have been put forward, but
its true mechanism remains unclariﬁed to this day .
Animal studies show that inhibitory input to the gut
causes dysmotility shortly after an operation. The hypothe-
sis behind it is that the activation of an inhibitory nonad-
renergic noncholinergic (NANC) pathway is the cause of
the main inhibitory effect in the gut. This happens after
abdominal surgery, where nitric oxide (NO) is considered as
the main neurotransmitter .
Nitric oxide is produced by three isoforms of NO syn-
thase; the endothelial (eNOS), the neural (nNOS), and the
inducible (iNOS) isoforms. Activation of iNOS directly
modulates intestinal dysmotility after bowel manipulation
and plays an essential role in initiating intestinal inﬂam-
mantion . We believe that inhibiting iNOS activity im-
proves intestinal motility after bowel manipulation.
It has been reported that S-methylisothiourea sulfate
(SMT) a more potent inhibitor of iNOS than aminoguani-
dine has a beneﬁcial effect on motility in the endotoxic
shock animal models. However, no information regarding
its effect on dysmotility in a postoperative, in vivo ileus
model has been available to date. This study was therefore
designed to ﬁnd out whether SMT also improved intestinal
motility after surgical bowel manipulation.
Compared with previously published studies our method
of evaluation places more emphasis on the transporting
function of the gut. Our results suggest that SMT can be a
useful prokinetic drug after abdominal surgery.
This study was approved by the Animal Care and Use
Committee of the Hamamatsu University School of Medi-
cine. All animals received humane treatment in compliance
with the “Guide for the Care and Use of Laboratory Ani-
mals” (National Institutes of Health publication No. 85-23,
revised 1985) and the “Guidelines for Animal Experimen-
* Corresponding author. Tel.: ϩ81-53-435-2276; fax: ϩ81-53-435-
E-mail address: firstname.lastname@example.org
The American Journal of Surgery 187 (2004) 93–97
0002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reserved.