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The treatment plan is highly individualized and is mainly
based on precise vessel anatomy, body weight, co-
morbidity and severity of ischemia.
© 2008 The WJG Press. All rights reserved.
Key words: Splanchnic ischemia; Mesenteric ischemia;
Tonometry; Blood ow; Chronic splanchnic syndrome;
Chronic splanchnic disease; Chronic mesenteric isch-
emia; Celiac artery compression syndrome; Ischemic
colitis
Peer reviewer: Dr. Daniel R Gaya, Gastrointestinal Unit,
Molecular Medicine Centre, School of Molecular and Clinical
Medicine, University of Edinburgh, Western General Hospital,
Crewe Road, Edinburgh EH4 2XU, United Kingdom
Kolkman JJ, Bargeman M, Huisman AB, Geelkerken RH.
Diagnosis and management of splanchnic ischemia. World J
Gastroenterol 2008; 14(48): 7309-7320 Available from: URL:
http://www.wjgnet.com/1007-9327/14/7309.asp DOI: http://
dx.doi.org/10.3748/wjg.14.7309
INTRODUCTION
In this review we will cover the current insights in
splanchnic or gastrointestinal ischemia. This disorder
is still rarely seen in daily practice, and randomized
controlled trials are absent, therefore the view of this
paper is highly personal and partly authority-based in its
conclusions. The spectrum of ischemic bowel disease
is broad, ranging from transient left-sided ischemic
colitis (with a good prognosis) to full blown intestinal
infarction, with a high death rate. We will focus on
new developments in clinical presentation, diagnostic
approaches, and treatment options. Splanchnic ischemia
can develop during low-flow states in patients with
patent vessels, and in subjects with varying degree
of splanchnic arter y stenoses or splanchnic venous
thrombosis. The prevalence of significant splanchnic
arterial stenoses, or chronic splanchnic disease (CSD) is
high, ranging from 30% to 50%[1,2]. Chronic splanchnic
sy ndrome (CS S) occurs whe n i sch emi c sy mpt oms
develop. The most characteristic ischemic symptoms
consist of postprandial pain, with resultant fear of eating
and weight loss. When epigastric bruit is included, these
are the so-called classical triad of CSS. In most patients
Jeroen J Kolkman, Marloes Bargeman, Department of Gastro-
enterology, Medisch Spectrum Twente, 7500 KA Enschede, The
Netherlands
Ad B Hu is man, Department of Interventional Radiology,
Medisch Spectrum Twente, 7500 KA Enschede, The Netherlands
Robe rt H Geelk erken, Department of Vascular Surgery,
Medisch Spectrum Twente, 7500 KA Enschede, The Netherlands
Author contributions: All authors contributed to this review
paper.
Correspondence to: Dr. Jeroen J Kolkman, Department of
Gastroenterology, Medisch Spectrum Twente, PO Box 50.000,
7500 KA Enschede, The Netherlands. j.kolkman@mst.nl
Telephone: +31-53-4872412 Fax: +31-53-4872979
Received: October 28, 2008 Revised: December 1, 2008
Accepted: December 8, 2008
Published online: December 28, 2008
Abstract
Splanchnic or gastrointest inal ischemia is rare and
randomized studies are absent. This review focuses on
new developments in clinical presentation, diagnostic
approaches, and treatments. Splanchnic ischemia can
be caused by occlusions of arteries or veins and by
physiological vasoconstriction during low-flow states.
The prevalence of signicant splanchnic arterial stenoses
is high, but it remains mostly asymptomatic due to
abundant collateral circulation. This is known as chronic
splanchnic disease (CSD). Chronic splanchnic syndrome
(CSS) occurs when ischemic symptoms develop. Ischemic
symptoms are characterized by postprandial pain, fear
of eating and weight loss. CSS is diagnosed by a test for
actual ischemia. Recently, gastro-intestinal tonometry
ha s b een validat ed as a d iag nos tic te st to det ect
splanchnic ischemia and to guide treatment. In single-
vessel CSD, the complication rate is very low, but some
patients have ischemic complaints, and can be treated
successfully. In multi-vessel stenoses, the complication
rate is considerable, while most have CSS and treatment
sh oul d b e strong ly con sid ered. CT and M R- bas ed
angiographic reconstruction techniques have emerged
as alternatives for digital subtraction angiography for
imaging of splanchnic vessels. Duplex ultrasound is still
the first choice for screening purposes. The strengths
and weaknesses of each modality will be discussed.
CSS may be treated by minimally invasive endoscopic
treatment of the celiac axis compression syndrome,
endovascular antegrade stenting, or laparotomy-assisted
retrograde endovascular recanalization and stenting.
Diagnosis and management of splanchnic ischemia
Jeroen J Kolkman, Marloes Bargeman, Ad B Huisman, Robert H Geelkerken
www.wjgnet.com
TOPIC HIGHLIGHT
Ioannis E Koutroubakis, MD, PhD, Assistant Professor of Medicine,
Series Editor
Online Submissions: wjg.wjgnet.com World J Gastroenterol 2008 December 28; 14(48): 7309-7320
wjg@wjgnet.com World Journal of Gastroenterology ISSN 1007-9327
doi:10.3748/wjg.14.7309 © 2008 The WJG Press. All rights reserved.
with CSS, this triad is incomplete. The true incidence of
CSS is currently unclear, but is rare compared to CSD
due to abundant collateral circulation.
Two important developments occurred in the
last decade. Firstly, validation of the gastric exercise
tonometry, which is currently the only clinically available
and validated diagnostic test to ascertain the presence
of splanchnic ischemia[3,4]. Using an ischemia-specific
test it should be possible (1) to identify patients with
symptomatic vessel stenoses, or CSS, which can be
treated, and (2) to make this diagnosis in time and
thus prevent the disaster of acute intestinal infarction.
Secondly, the increasing evidence that one vessel CSD
may cause splanchnic ischemia resulting in one vessel
CSS, and can be successfully treated with appropriate
selection procedures[5]. An important difference in
presentation, treatment and outcome has been shown
to exist between single and multi-vessel disease[6]. In the
latter group, the clinical presentation is often less typical,
with diarrhea, unexplained gastric ulcers, or dyspepsia-
like symptoms. These insights stem mainly from our
work with tonometry.
An entirely different entity consists of patients
suffering from splanchnic ischemia without splanchnic
ste nose s; th e so-c alled non-o cclu sive mese nteri c
ischemia (NOMI). It can be seen as a consequence of
physiological adaptation mechanisms during low-flow
states were blood is dispersed from the gastrointestinal
region to more vital organs[7]. This situation is very
common in intensive care and operative units, but
can also be seen in outpatients. Treatment consists of
aggressive uid resuscitation and medication. However,
bowel infarction can still occur.
In t he last d ecade a change i n imagin g of the
spl a nchni c vesse l s occurred . Duplex u ltraso u nd,
although operator dependent and suitable for 80% of
patients, is still the first choice. Visceral angiography
has increasingly been replaced by CT and MR-based
angiographic reconstruction techniques. The clinically
im porta nt a dva ntag e s an d dis advantag es o f thes e
techniques will be discussed. Whichever technique is used,
it leaves the clinician with only anatomical information.
To decide whether a given steno sis has cau sed the
symptoms, information on actual ischemia is required.
This information can be obtained using tonometry,
which has a proven accuracy of 80%-90%. Other tests
including, serological iFABP, endothelial progenitor cell
measurement, or MR angiography (MRA)-based saturation
measurements, may serve that purpose in the near future.
Treatment options have changed considerably over
the last decade. Apart from the classical transabdominal
vascular reconstructive surgery techniques, minimally
invasive endoscopic treatment of the celiac axis comp-
ression syndrome, endovascular antegrade stenting, or
laparotomy-assisted retrograde endovascular recanali-
zation and stenting have broadened our therapeutic
“armory” considerably. The main patient characteristics
to guide therapy choice, which inc lude anatomical
considerations, as well as body weight, co-morbidity and
severity of ischemia, will be discussed.
EpIDEmIOlOgy
The prevalence of CSD is not insignificant, and rises
with increasing age. In a 30-year-old angiographic study
of 713 patients, 5% of the splanchnic arteries were
occluded and in 70% of these occlusions the IMA was
involved[8]. In a retrospective study including 980 patients
with a mean age of 68 years who underwent angiography
for various indications, 8% had signicant stenoses of at
least one splanchnic artery[9]. In a screening study with
duplex ultrasonography in 553 healthy elderly subjects
with a mean age of 84 years, stenoses in the celiac artery
(CA) or superior mesenteric artery (SMA) were found
in 18%[10]. In patients with atherosclerotic disorders of
aorta, iliac and femoral vessels the incidence ranged
from 25% to 40%[11,12].
A minority of patients with CSD will develop CSS
or acute splanchnic syndrome (ASS). A follow-up of
the study in elderly subjects in whom duplex had shown
CSD, revealed no CSD-related mortality after 6 years of
follow-up[13]. This risk is increased in subjects with 2 and
3 vessel CSD. In the study by Thomas et al 4.5% of pa-
tients with three-vessel CSD developed CSS and another
1.5% died of ASS after a follow-up of an average of
2.6 years[9]. In the Detroit experience, of the 23 patients
with severe acute intestinal ischemia studied between
1963 and 2000, 12 (52%) patients had undetected CSS
symptoms well before presentation[14].
ANATOmy AND (pAThO)-physIOlOgy
Anatomy
Three major arteries supply blood to the stomach, small
intestine and colon. The first branch, the celiac artery
(CA) supplies the stomach, proximal duodenum, liver
and spleen. The second, the superior mesenteric artery
(SMA) supplies the distal duodenum, small intestine
and proximal colon. The third b ranch supplies the
distal colon and the rectum. There is an abundance of
collateral vessels to protect the gastrointestinal tract
from ischemia. Branches of these arteries enter the
serosa of the gut on the mesenteric side and form a
vascular plexus around the gut. After penetration of the
bowel wall, a dense submucosal plexus is formed. From
this plexus, arterioles penetrate the muscularis mucosa
to the supercial mucosal layers. At the mucosal tip they
branch into an intense capillary network of capillaries
and venules. Each villus has a single, central arteriole.
This arteriole travels to the tip of the villus, then splits
into a network of capillaries, which form a central venule
at the base of the villus. This is why countercurrent
exchange can take place[15]. The tip of the villus is quite
susceptible to ischemia[16].
Blood ow
Under normal conditions, approximately 20% of the
cardiac output goes through the splanchnic vessels.
This splanchnic blood flow doubles after a meal to
approximately 2000 mL/min. Blood draining from the
bowel enters the splanchnic veins and nally drains into
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the portal vein. The liver, therefore, receives its blood
supply from two sources: venous blood from the portal
vein and arterial blood from the hepatic artery, which
branches from the CA in 75% and from the SMA in
remaining 25%. This dual blood supply renders the
liver relatively protected against ischemia. When the
blood ow to the bowel decreases below a certain level
(the critical O2 delivery level), the cells will switch to
anaerobic glycolysis, resulting in lactate production[17]. In
the gastrointestinal system this occurs when blood ow
is reduced below 50% of the basal rate[18,19]. In most
cases of splanchnic ischemia, the arterial lactate levels
will remain normal despite increased lactate production
by the gut. The reason for this discrepancy is the large
lactate metabolizing capacity of the liver. Thus, systemic
lactic acidosis is a late phenomenon in these patients,
indicating severe transmural ischemia and probably liver
involvement as well.
The regulation of the splanchnic blood ow involves
both vasoconstrictive and vasodilating substances. The
main vasoconstricting substances are the catecholamines
and endothelin, especially endothelin-1[20,21]. The main
splanchnic vasodilators are nitric oxide (NO) and
prostaglandins. It is assumed that part of the gastroi-
ntestinal toxicity of NSAIDs can be attributed to vaso-
constriction because of reduced mucosal prosta-glandin
concentration[22].
During low-ow states, splanchnic vasoconstriction
is an early and profound phenomenon[23], which may
lead to blood ow reduction below the 50% threshold.
Splanchnic ischemia develops well before systemic
hemodynamic instability arises[24]. This splanchnic vaso-
constriction may be triggered by shock states, including
hemorrhage, sepsis, dehydration or cardiac failure, from
vasoactive medications, nicotine and cocaine abuse, or
even in strenuous exercise[19,25-27] or severe psychological
stress[28]. This combination of ischemia despite normal
vessel anatomy, has given rise to the term non-occlusive
mesenteric ischemia (NOMI).
Ischemic and reperfusion damage
After the onset of ischemia, an ischemic and reperfusion
phase can be distinguished. When this ischemia lasts for
less than 6-8 h all processes are reversible; thereafter,
transmural gangrene may be the result of completely
interrupted blood ow. The ischemic phase starts when
the energy-containing ATP is depleted due to lack of
oxygen, leading to disruptions of the tight junctions. Also,
membrane-bound enzymatic pumps stop functioning,
leading to inflow of luminal electrolytes and water into
epithelial cells resulting in cell death. Both effects lead
to reduced intestinal epithelial barrier function, with
bacteria and other luminal contents entering the blood
stream[29]. At the same time, the mucosal enzyme xanthine
dehydrogenase is converted to xanthine oxidase (XO),
which at this stage is harmless. These early effects of
the ischemic phase alone are localized and can remain
clinically undetected for many hours. The reperfusion
phase star ts when oxygen-enriched blood re-enters
the ischemic tissue. This reperfusion may begin after
partial dissolution of an embolus or thrombus or after
revascularization. This oxygen is transformed into reactive
oxygen species (ROS) by the abundantly present XO.
ROS are toxic to proteins and DNA[30], and diffuse into
tissues, leading to intensification and spreading of the
damaged area. This so-called ischemia-reperfusion cascade
initiates an inammatory and thrombotic response in the
submucosal layer of the villus. In the future, antagonists
of leukocyte vessel wall adhesions, an early event in
the ischemia-reperfusion cascade, could attenuate these
inflammatory and thrombotic responses[31]. Successful
restoration of splanchnic blood flow, containing toxic
products, from the ischemic area into the systemic
circulation might trigger multiple organ failure.
ClINICAl pREsENTATION
The naming of gastrointestinal ischemic syndromes is
often confusing and requires a brief introduction. We
will divide the different syndromes based on duration of
complaints and vessel abnormalities (Figure 1). Acute
splanchnic syndrome (ASS; synonym: acute mesenteric
ischemia, acute bowel infarction) is characterized by
a sudden onset of abdominal pain due to interrupted
splanchnic circulation. It consists of occlusive disorders:
acute splanchnic emboli, venous thromboses and end-
stage ar terial t hromb otic occlusions, and the non-
occlusive disorder, NOMI. Chronic splanchnic syndrome
(CSS) is dened by a combination of chronic splanchnic
disease (CSD) with ischemic symptoms. Celiac artery
co m pres sion syn drome (CACS) is d efine d by the
combination of eccentric celiac artery compression
by the arcuate ligament of the diaphragm and chronic
abdominal symptoms caused by ischemia. NOMI may
be diagnosed with chronic or remittent splanchnic
hypoperfusion, for example in heart failure[32] or in
dialysis patients[33]. Finally, ischemic colitis is a separate
entity and will be discussed separately.
Acute splanchnic syndrome
Acute spl anchnic ischemia can result from ar terial
thrombosis, acute embolism, venous thrombosis or non-
occlusive ischemia[34-39]. Most often the superior mesenteric
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Kolkman JJ
et al
. Diagnosis and management of splanchnic ischemia 7311
Gastrointestinal ischemia
Acute Chronic
Occlusive Non-occlusive Occlusive Non-occlusive
ASS, embolism
ASS, thrombosis
ASS, venous
thrombosis
ischemic colitis
(right-sided)
NOMI
ischemic
colitis
(left-sided)
CSS,
single-vessel
CSS,
multi-vessel
CACS
NOMI
Figure 1 Classication of splanchnic, or gastrointestinal ischemia. ASS:
Acute splanchnic syndrome; CSS: Chronic splanchnic syndrome; CACS, Celiac
artery compression syndrome; NOMI: Non-occlusive mesenteric ischemia.
artery is involved. Clinically, it is recognized by an acute
onset of abdominal pain, which might be accompanied
by nausea, vomiting and hypotension. On physical
examination and laboratory testing there are usually
minimal abnormalities at first[4 0]. If left untreated, the
pain often disappears. Without restoration of blood ow
and depending on the collateral circulation, a full blown
peritonitis follows within hours or days, with translocation
of bacteria and SIRS, or systemic inammatory response
syndrome, and multiple organ failure. Mortality is high,
ranging from 32%-80% depending on the etiology. In the
last four decades a reduced mortality rate was observed
for venous thrombosis and arterial embolism (now 32%
and 51%), while the mortality of NOMI and arterial
thrombosis remained unchanged at 73% and 77%[39].
Therefore, the most important factors for improvement
of survival should be a high index suspicion, a proper
diagnosis of CSS before ASS develops and an immediate
restoration of blood ow.
Chronic splanchnic syndrome
Chronic splanchnic syndrome (CSS), a synonym for
chronic mesenteric ischemia, gastrointestinal ischemia
or intestinal angina, is a relatively rare disorder and
may b e u n d e r-diagnos e d . A f t er in s t itution of a
multidisciplinary approach team for the evaluation of
insufciently explained abdominal pain in the Medisch
Spectrum Twente Hospital, the recognition of CSS
increased from seven to 23 persons per million per
year[41]. The major symptoms of CSS are outlined in
Table 1. The most characteristic is postprandial pain,
starting 15-30 min after a meal, and persisting for 1-3 h.
Patients often report fear of eating, and take smaller
meals, with less fat and proteins. Weight loss, the second
characteristic finding in CSS, is almost always caused
by reduced intake due to this fear of eating and not to
malabsorption. Diarrhea, unexplained gastric ulcers or
even gastroparesis can also be presenting symptoms.
This multidisciplinary team, with nationwide
referrals, also found a differentiation between single- and
multi-vessel disease[6]. Although the clinical presentation
is quite similar, the course and outcome justies separate
discussion of both groups[42].
Single-vessel disease
The etiolog y of isolated stenoses of the splanchnic
arteries, most often the celiac artery, is caused in
most cases by splanchnic arteriosclerosis or external
compression by the crux of the diaphragm[5]. Due to the
presence of abundant collateral vessels, it was generally
assumed that a single stenotic lesion rarely, if ever,
causes complaints[43]. In 1972, Szilagyi et al[44] reviewed
the entire liter ature on CA compression syndrome
and found no proof of any abnormality of intestinal
structure or function that could be attributed to this
compression, nor proof that treatment had more than a
placebo effect. However, several papers were published
with good results for CA decompression operations[45-47].
These opinions were challenged recently by our group.
We have shown that by using tonometry as a functional
test, we could successfully distinguish patients that
benefited from surgery from those who did not, and
that the disappearance of symptoms after successful
revascularization was associated with normalization of
this functional test[5]. The prognosis of single-vessel
CSS seems rather benign. In 50 patients with an isolated
stenosis, no mortality and low post-operative morbidity
were seen on follow-up, which contrasts sharply with
multi-vessel CSS[6]. No difference in short-term outcome
between patients with CACS or atherosclerotic lesions
was observed. In our view, single-vessel CSS can be
diagnosed when (1) there is a significant stenosis on
duplex ultrasound or angiography (> 70%), (2) the
clinical history ts CSS and (3) the functional test (gastric
exercise tonometry) indicates splanchnic ischemia.
Multi-vessel disease
Wh en 2 o r 3 of the main splanchnic arte rie s h ave
signicant stenoses the ratio of CSS versus CSD increases
to almost 90% in patients referred to our unit (unpublished
data). Although the clinical presentation is in essence not
very different from patients with single vessel disease,
(postprandial pain and weight loss as the main symptoms)
sometimes quite atypical presentations can be seen. Even
experienced clinicians can miss an adapted lifestyle that
masks a case of slowly progressive CSS. In multi-vessel
CSS the clinical presentation can mimic simple dyspepsia
with bloating and fullness, gastroparesis, unexplained
diarrhea or simply lack of energy. When the disease
progresses, the pain may be provoked by small triggers
such as a simple drink, or even during rest. Abdominal
vascular resting pain, persisting abdominal pain not
related to a meal, are important prognostic indicators, and
often indicate imminent or ongoing bowel infarction, or
ASS. It should be remembered that the time to develop
irreversible ischemic changes is about 6-8 h in end-stage
2- or 3-vessel CSS.
Ischemic colitis
There are two types of ischemic colitis: left-sided and
right-sided ischemic colitis. Left-sided ischemic colitis
usually presents with abrupt onset abdominal pain,
followed by bloody diarrhea, which may persist for days
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Table 1 Clinical picture in 107 CSS patients[6]
Patient characteristics in 107 CSS patients
Age Mean 55 years, range 18-85
Male:Female 26%:74%
Duration of symptoms Mean 18 mo, range 3-192
Reported weight loss 78%
BMI Mean 20.8 kg/m2, range 12.0-33.2
BMI < 20 kg/m235%
Weight loss (kg/mo) Mean 1.3 kg/mo, range 0-8
Pain after meal 86%
Pain after exercise 43%
Abdominal buit 24%
Classical abdominal angina 22%
Cardiovascular history 40.20%
Nicotine use 45.80%
to weeks. It is often associated with low-ow states[48],
coagulation disorders[49], cardiac abnormalities or after
abdominal aor tal surger y. Low -flow states m ay be
induced by arrhythmias or cardiac dysfunction, drugs,
dehydration or (aortic) surgery. Isolated right-sided
ischemic colitis usually presents with abdominal pain,
but rarely with bloody diarrhea[50]. Right-sided ischemic
colitis is usually associated with SMA stenosis or
occlusion. It should therefore be considered as part of
CSS or ASS.
The late stages of ischemic colitis can be a clinical
challenge, with clinical presentation and endoscopic
findings mimicking both Crohn’s disease and ulcerative
colitis. In most cases isolated ischemic colitis will be
transient, although persistent colitis, stricture formation
and even gangrenous colitis have been seen to develop[48].
NOMI
NOMI h a s a l r eady been mentioned a s c a u s e of
ASS in 20%-30% of patients. Most NOMI patients
however, never develop ASS, and this condition is quite
common due to the early splanchnic vasoconstriction
with reduced circulating blood volume of any cause.
Moreover, the bowel has limited capacity to preserve
aerobic metabolism. NOMI is very common and widely
recognized in intensive care and peri-operative medicine,
wh ere it is referr ed to as int ramuc osa l a cid osis or
mucosal ischemia[7]. Here, the clinical signs of NOMI
may range from abdominal tenderness, nausea, diarrhea,
ulceration, bleeding and full thickness ischemia, and may
lead to bowel wall necrosis and even death. In critically
ill patients, this process can easily lead to translocation
of bacteria and endotoxins, causing SIRS and multi
organ failure[51].
We al so distingu ished a g roup of pa tients w ith
‘a bdom inal mig r aine ’ ch arac teri zed by symp toms
compatible with splanchnic ischemia, abnormal functional
te sts (to nometry) indi cat ing isc hem ia, spl anchnic
angi ography without r elevant pathology, and good
response to vasodilators[4,52].
DIAgNOsTIC mEThODs
Duplex ultrasound
Duplex-ultrasound is widely used as screening tool for
detection of splanchnic stenosis. In experienced hands
the CA and the SMA can be visualized in 80%-90% of
patients. Proper visualization can be difcult because of
the location behind the, often air-filled, stomach. First,
vessel anatomy is established using the B-mode. This
is followed by assessment of blood-flow pattern and
velocity. The arterial blood-ow in the splanchnic vessels
varies during the cardiac cycle. The normal CA has a
biphasic signal. Retrograde ow in the common hepatic
artery may indicate proximal CA stenosis or occlusion.
The SMA normally has a triphasic signal. A biphasic signal
in the SMA is normal after a meal or when the right, or
rarely the common hepatic artery, comes from the SMA
as an anatomic variant; it may indicate a proximal stenosis
if it occurs in the fasting state. Blood-ow measurement
is performed using a measurement angle of less than 60
degrees. A signicant stenosis is characterized by areas of
high velocity jets (small streaks of very high, sometimes
turbulent flow) within the artery, and overall increased
flow ve locity. T he widely a cce pte d cut-off va lues,
published by Moneta in 1993, are: for the CA a Peak
Systolic Velocity (PSV) and End Diastolic Velocity (EDV)
of 200 m/s and 55 m/s; and for the SMA, PSV and EDV
of 275 and 45 m/s, respectively[53]. Using these threshold
values, the sensitivity and specicity for stenoses > 70%
were 89% and 44% for the inspiration CA, 89% and 62%
for the expiration CA, 100% and 61% for the inspiration
SMA, and 80% and 42% for the expiration SMA. One
criticism of the “Moneta criteria” has been that he used a
cohort from the general population with atherosclerotic
disease, who did not necessarily suffer from chronic
abdominal symptoms. In daily practice, duplex ultrasound
is performed under fasting conditions. Some studies
suggested measurement after test meals, because patients
with ischemia had suppressed augmentation of blood-
ow following a meal compared to subjects with normal
vessels[54-58]. Until recently, post-test meal splanchnic
duplex made no headway in daily practice. Duplex-derived
ow velocities after splanchnic artery bypass grafting may
be affected by graft diameter or type of reconstruction
and are not equal to the preoperative criteria[59].
MRA
By using contrast, so-called contrast enhanced (ce)-MRA it
is possible to identify splanchnic artery stenoses and even
collaterals, for example Riolan’s artery[60-62]. Surprisingly,
we could identify only two studies that compared digital
subtraction angiography (DSA) with MRA in 19[63] and 23
patients[61] with good correlation. In our own experience,
with 25 patients in whom DSA and MRA were performed
within 2 mo, the MRA had a 95% sensitivity and 90%
specicity, compared to DSA as the “gold standard”. We
observed a significant inter and intra observer variation
in grading of stenoses in 45% of the cases[64]. Although
widely used, it can therefore not be considered a gold
standard investigation for assessment of vessel anatomy.
A potential advantage of MRA is its ability to measure
actual ow through the splanchnic and portal circulation.
The arterial flow is harder to measure than in veins,
because of the smaller caliber and the pulsatile character
of arterial flow[5 6]. However, a consistent relationship
between ow in the arteries and veins was observed[65,66].
Several studies with healthy volunteers and patients have
shown augmentation of ow after a meal and signicant
differences between patients with vessel stenoses and
healthy volunteers[54,58]. These results may be promising
for future use in diagnosing CSS.
CT angiography
With the introduction of the multi-slice CT scan, CT
angiography of the abdo minal ar teries has beco me
possible. There are several studies showing that CT
angiography is an accurate way to image the splanchnic
arteries, veins, and collaterals
[67-70]
. Surprisingly, studies
focusing on CSD and comparing this technique to the gold
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Kolkman JJ
et al
. Diagnosis and management of splanchnic ischemia 7313
standard (DSA) in a representative group of patients, are
lacking to our knowledge. It is essential to use multi-slice
scanners with slice thicknesses of 2 mm at most (preferably
1 mm) to allow accurate visualization of the arteries. With
the state-of-the-art technology, CT-scanning in inspiration
and expiration is possible and is a prerequisite when there
is suspicion of celiac artery compression syndrome. The
advantages of CT angiography are clear: in a patient
with acute abdominal complaints it can show or exclude
arterial and venous obstruction, bowel involvement
(wall distention and thickening, presence or absence of
contrast enhancement, pneumatics), as well as alternative
diagnoses. Among these are perforations, pancreatitis, and
abscesses. Similarly, in the setting of chronic unexplained
postprandial pain, CT angiography may also show
alternative diagnoses. In our experience, these include
pancreatitis, pancreatic cancer, and retroperitoneal tumors.
Adding the advantages of minimal invasiveness and lower
costs, CT angiography can be a serious competition for
conventional angiography
[67,69,71,72]
.
Angiography
Intra-arterial digital subtraction angiography (DSA)
of the spla nch nic vessel s c an be u sed to perf orm
endovascular therapeutic procedures in the same session,
including infusion of papaverine and angioplasty
or stenting of sten ose s. The combina tio n o f hig h
diagnostic accuracy and the possibility for intervention
makes angiography the procedure of choice in patients
susp e c t e d of sym p t o m a tic splanch n i c st e noses,
especially with imminent or ongoing infarction. In acute
splanchnic infarction, angiography serves as guideline
for endovascular or operative revascularization.
A state-of-the art visceral angiography involves three
steps: (1) a non-selective anterior-posterior abdomi-
nal aortic angiography. When collaterals show in this
stage, they indicate signicant splanchnic artery steno-
sis and are considered pathological (Figure 2A and B);
(2) a lateral aortography during maximal inspira-
tion and expiration, for detection of external com-
pr essi on o f t he C A an d/or, r arel y, th e SMA ; and
(3) selective angiography of all three splanchnic vessels
to obtain a detailed view of the vascular anatomy, steno-
ses and anatomical variations[42]. Although CT and MR
angiography are gaining ground as the principal investi-
gative tools for splanchnic vessel anatomy, detailed an-
giographic information of anatomy, stenosis, collaterals
and anatomical variations is, in our view, essential in the
preparation of an optimal revascularization strategy.
Endoscopy
Although almost all patients with CSS underwent upper
GI endoscopy during the work-up of their complaints,
abnormalities were rarely noted. Reports on gastroparesis
and gastric gangrene have been published, but are also
rare. In our experience, 7% of patients with CSS presented
with unexplained gastroduodenal ulcers (Helicobacter
negative, no NSAID-use). In colonic ischemia endoscopy
is the mainstay of diagnosis. The typical picture consists
of superficial ulceration, mucosal friability, edema, and
patchy areas of either bleached or cyanotic mucosa[73,74].
Colonic ischemia of longer duration may mimic ulcerative
colitis or even Crohn’s disease. Some papers have focused
on endoluminal light spectroscopy oximetry. With this
technique, mucosal hemoglobin oxygen saturation can be
measured[75-80]. In a recent study it was shown that mucosal
saturations are low in patients with chronic splanchnic
ischemia, compared to healthy subjects. After successful
treatment in these patients, mucosal oxygen saturations
increased substantially[76]. There are a several potential
limitations to this technique. Firstly, ischemia is patchy in
nature, and can therefore be missed. Secondly, ischemia
might be present in parts of the small bowel that are
difcult to reach endoscopically. Thirdly, ischemia might
only be present in a situation of increased oxygen demand
(after a meal, or during exercise), especially earlier in the
course of the disease.
Tonometry
Tonometry of the gastrointestinal tract has the unique
potential to the detect ischemia, irrespective of flow or
metabolism. Tonometry is based on a general physiological
principle that during ischemia, anaerobic metabolism
leads to increased production of acids, which are buffered
locally by bicarbonate ions, leading to increased carbon
dioxide tension (PCO
2
) in the tissue. This relation between
7314 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol December 28, 2008 Volume 14 Number 48
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Figure 2 Collateral vessels: gastroduodenal (GD) artery and Buehlers artery (B). A: The gastroduodenal (GD) artery and Buehlers artery (B) are visible on
non-selective aortography indicating stenosis of the origin of either the CA or SMA. The late lling of the CA points to a stenosis in its origin; B: Lateral aortography
showing an asymmetrical stenosis of the CA; C: On selective cannulation of the SMA, both collaterals are more clearly visible.
A B C GD
B
→
→
ischemia and increased PCO
2
has been observed in all
ischemic models and animals studied. The most specic
marker of ischemia is an increased difference between
luminal and arterial CO2, the PCO
2
gradient, which is
barely influenced by other systemic factors, including
hyper- or hypoventilation. The luminal PCO2 can be
measured conveniently using a nasogastric tonometry
catheter and air tonometry (Figure 3). The unique property
of tonometry in measuring ischemia per se
[3]
sets it apart
from all other diagnostic methods. Indeed, when blood
flow is gradually reduced, the PCO2 gradient remains
normal until the blood ow decreases to < 50% of the
basal ow and then increases sharply
[18,19]
.
In patients with suspected chronic ischemia, gastric
tonometry has been used initially using a test meal with
variable, but overall disappointing, results[81-83]. The main
methodological problems involved buffering effects
by gastric acid and dilution effects of the ingested test
meals[84]. We therefore developed a t onometric test
involving 10 min of submaximal exercise, in order to
provoke GI ischemia[19]. The diagnostic accuracy of the
gastric exercise tonometry test (GET) was evaluated in
a cohort of patients referred for suspected CSS. GET
had a 78% sensitivity and 92% specificity for ischemia
detection[4]. We have used GE T to guide treatment
in patients with single vessel stenoses. The main
finding in this study was the tight relationship between
normalization of GET and disappearance of symptoms
after anatomically successful revascularization[5]. We
also re-examined the potential use of a 24-h tonometry
test, including test meals, with standardization of the
test circumstances, including potent acid suppression
and standard test meals[85]. In a pilot study in 33 patients
referred for suspected CSS, the 24 h tonometry showed
pr omising result s, wit h a se nsitivit y o f 76% an d a
specificity of 94%, comparable to those of exercise
testing[86]. We are now analyzing a study comparing
GET and 24-h tonometry. The preliminary data suggest
that 24-h tonometry permits accurate measurement
of postprandial and fasting PCO2 levels; following
meals, gastric and small bowel PCO2 gradients may
physiologically increase up to 10 kPa. During ischemia,
gradients exceed 11 kPa (60 mmHg)[87]. Also, prolonged
PCO2 increases for several hours (up to 7 h in one subject,
Figure 4), especially in combination with abdominal pain
during fasting, indicate imminent infarction, and thereby
provide invaluable extra information.
Serological markers
Cu r ren tly, th ere is no rel iable m arker to diagnose
gastrointestinal ischemia. Studies have been performed
using several markers, including (L and D)-lactate, LDH,
D-dimer; however, none of these was proven to be
sensitive or specific. In contrast, various animal models
have successfully used markers like D-lactate and i-FABP
(intestinal Fatty Acid Binding Protein) as an early marker
of intestinal ischemia. This enzyme is present in the
mature enterocytes of the small intestine, in the highest
concentration at the villi[88,89], the region most susceptible
to ischemia, and is released early after an ischemic insult.
Therefore it seems a good candidate marker for early
ischemia detection[90]. There are a few patient studies
indicating its potential as marker for ASS[89,91], but also
during pancreatitis[92] or inammatory bowel disease[93]. We
performed a pilot study comparing tonometric responses
to a test meal and indeed found increased i-FABP in these
subjects[94]. More studies are needed before the role of this
and other promising plasma markers can be established.
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Kolkman JJ
et al
. Diagnosis and management of splanchnic ischemia 7315
Figure 3 Tonometer balloon placed in the stomach nasogastrically. CO2
diffuses rapidly over different membranes, therefore the tonometer PCO2
(PtCO2) will be in equilibrium with gastric luminal PCO2 (PgCO2) and mucosal
PCO2 (PmCO2). The PCO2 can be measured from the catheter either from
injected saline using blood gas analyzers or by connection to a semi-automated
Tonocap device. The underlying physiological principle is that ischemia is
always associated with PCO2 increase. Therefore, focal measurement of
ischemia is possible for long periods via a minimally invasive technique.
PtCO
2
PgCO
2
PmCO
2
20
18
16
14
12
10
8
6
4
2
0
PrCO2-PaCO2 (kPa)
13 14 15 16 17 18 19 20 21 22 23 24
1 2 3 4 5 6 7 8 9 10 11
A
15
16
17
19
20
21
22
23
0
2
3
4
5
6
7
9
10
11
12
13
14
20
18
16
14
12
10
8
6
4
2
0
PCO2 (kPa)
B
Figure 4 Imminent ASS and normal gastric and jejunal PCO2 pattern. A:
Normal 24 h PCO2 pattern in the stomach (squares) and jejunum (diamonds)
with variation in PCO2, but no peaks above 11 kPa following meals; B: Imminent
bowel infarction in a patient with severe 3 vessel CSS. After her evening meal
she had pain for almost 6 h, and extreme ischemia with PCO2 > 16 kPa for
7 h. She was treated with endovascular stent placement the day after this
measurement, with immediate relief of complaints. She is still doing well, over 3
years later.
bridge to open repair after full recovery and weight gain in
selected young patients with end stage CSS.
Acute splanchnic syndrome
Th e diagnosis of ASS begins with a high index of
suspicion. Any patient with acute onset of abdominal
pain that remains unexplained after proper investigation
for two hours should be suspected to have ASS. An
urg ent i nve stig a tion of ves sel p aten cy sh ould be
ordered. The choice is between an acute angiography
and a CT scan. Simultaneously with the CT scan or
DSA, the volume status should be aggressively restored
to counterbalance the splanchnic vasoconstriction,
which is almost always present in these patients. All
necrotic bowel should be removed and blood flow
restored as soon as possible. The latter will involve
intravenous heparin in venous ASS, revascularization or
embolectomy in arterial ASS, and in selected cases, intra-
arterial vasodilation in ASS-NOMI[73]. In arterial ASS,
the choice of revascularization, and whether it should be
done before or after bowel resection, depends on local
expertise. Bowel vitality can be hard to assess initially,
therefore second- and third look operations to ascertain
bowel vitality are often advised and seem prudent. It
has been shown that aggressive treatment might be
responsible for the modest improvement in outcome
of ASS[39]. In cases of limited extent of severe bowel
ischemia we advise immediate retrograde endovascular
revascularization[99,100] and resection of the ischemic
bowel to diminish the detrimental cascade of ischemia-
reperfusion resulting in multi organ failure and high
mortality.
Acute ischemic colitis
Isolated acute left-sided ischemia can usually be treated
conservatively, as it is almost always non-occlusive in
nature. Right-sided ischemic colitis should be considered
as ASS and treated accordingly. Patients with left-sided
ischemic colitis should be treated with intravenous
fluid and bowel rest. Broad spectrum antibiotics are
advised, which might reduce bowel damage[48,101], but
there is no evidence to back this up. Left-sided ischemic
colitis subsides in 2 wk[48] in most patients. About 20%
of patients with acute ischemic colitis ultimately need
surgery, either because the ischemic colitis persists
or complications occur. A non-responsive left-sided
ischemic colitis can manifest as ongoing sepsis refractory
to medical treatment, persistent diarrhea, bleeding, or
protein-losing enteropathy for more than 14 d. In some
patients progressive peritonitis or gangrene of the colon
develops, with a mortality rate of 30%-60%[48,102].
ChRONIC splANChNIC syNDROmE
Single-vessel CSS and CACS
Patient selection is crucial in these patients. When single-
vess el CSS i s diagnosed by history, vess el anato my
and functional tests, treatment may help to relieve the
symptoms. The prognosis quod vitam is good; therefore
WORk-Up AND TREATmENT
In the work-up of patients in whom splanchnic isch-
emia is suspected four questions should be addressed:
(1) is the history compatible with splanchnic ischemia,
(2) which of the three vessels are narrowed, to what de-
gree and are pathological collaterals present, (3) is there
(functional) evidence of actual ischemia, and (4) is the
impairment of the splanchnic blood ow in the short-
term threatening for the bowel.
Endovascular techniques have emerged allowing for
stent placement in CA and SMA in most patients. The
choice is between dilation or stent placement. Dilation
alone has a low short-term success rate, and we currently
use it only as diagnostic tool to distinguish between CSS
and CSD. Although some vessels can be treated via the
femoral artery; the sharp downward angulation (60 de-
grees) of the AMS and CA often necessitates brachial
artery cannulation in many cases. In our center, both
techniques are often combined, using the femoral cath-
eter as a guide for the stent placed via the brachial cath-
eter. Compared to operative revascularization, the main
disadvantage of stent placement is the shorter long-term
patency. The latter was shown in three recent studies,
of which two compared endovascular and open repair.
Atkins et al reported in a cohort of 80 patients with CSS
primary patency at 1 year of 58% after endovascular and
90% after open repair and a primary assisted patency of
65% vs 96% respectively[95]. Bieble et al reported that in a
cohort of 49 patients with CSS, 75% after endovascular
and 89% after open repair were symptom free after 2
years[96]. The main difference in this study was the reste-
nosis rate of 8% after open versus 25% after endovascu-
lar treated patients, with lower complication rates in the
latter. Sarac et al[97] reported a primary, primary assisted
and secondary patency of 65%, 97% and 99% in a co-
hort of 87 endovascular treated splanchnic arteries. The
low short-term morbidity makes it an excellent choice in
patients with limited life expectancy or those too weak
or underweight for operative revascularization.
A variety of surgical techniques have been advocated
for open repair of the splanchnic arteries, including re-
implantation, transarterial and transaortic endarterectomy,
antegrade and retrograde aortovisceral bypass using vein
or arterial autograft bypasses and prosthetic bypass, with
early success rates between 91% and 96% and late success
rates between 80% and 90%[98]. The choice of technique
is usually based on the preference and experience of the
surgeon. However, the majority of centers with wide ex-
perience believe that antegrade autogenous revasculariza-
tion techniques of both the CA and the SMA in selected
cases offers the best long-term results. The disadvantage
of major aortic surgery is the not inconsiderable burden
for the patient. In general, we prefer antegrade two-vessel
reconstruction for young patients with CSS and a body
mass index above 19.5 kg/m2, and endovascular or mini-
mal invasive retrograde single or multi-vessel reconstruc-
tions for patients with relevant comorbidity or reduced
life expectancy. Also endovascular repair could act as
7316 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol December 28, 2008 Volume 14 Number 48
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treatment is aimed at relief of symptoms only. Some
patients prefer conservative measures including small meals
and proton pump inhibitors. When a revascularization
is indicated, the choice of technique depends on vessel
abnormalities as well as local experience.
In CACS patients primary stent placement is not
an option because the repeated force by the diaphragm
with each respiration will fracture the stent in the short-
term. Different techniques are currently used to release
the CA from compression by the diaphragm’s crux. One
potential complication is the development of reflux
disease[5], which is related to the damage to the crux,
which also plays an important role in the physiological
anti-reflux barrier. Recently, we have perfor med the
release by an endoscopic retroperitoneal technique with
equally good results compared to the open approach in
the short-term[103]. The problem of reux seems to be
reduced, although more studies with longer follow-up
times are needed.
Multi-vessel CSS
Most patients with abdominal symptoms and multi-
vessel stenoses have, in our experience, CSS. The risk
of developing ASS is considerable[6], there fore the
treatment goal is aimed at symptom relief as well as
prevention of ASS. There are no prospective studies on
the conservative treatment of CSS, but advice on diet
and lifestyle have been described. Most patients have
already changed their eating pattern, with smaller and
more frequent meals that contain less fat and protein. It
should be strongly advised to stop smoking because it
causes strong splanchnic vasoconstriction. The use of
proton pump inhibition is not evidence based, however,
it makes sense as these drugs reduce the secretion of
gastric acid, and thus gastric metabolic demand, while
increasing the gastric blood flow[104]. Atherosclerosis
is a generalized disorder; therefore the usual measures
should be initiated including treatment of hypertension,
hyperlipidemia, and diabetes.
Most multi-vessel CSS patients have an indication
for revascularization. Whether patients with multi-vessel
(asymptomatic) CSD should be treated to prevent ASS
is uncertain. It may be considered in young patients in
good health, but rm evidence is lacking. The choice of
revascularization in multi-vessel CSS again depends on
anatomy, experience, and comorbidity as discussed before.
NOMI
Chronic splanchnic ischemia due to NOMI comes in
two different patient groups. The rst group has severe
underlying medical conditions, with reduced effective
circulating volume and splanchnic vasoconstriction
and ischemia. These include dialysis patients[33 ] and
chronic heart failure[32] patients. Treatment is difficult
be cau se the tre atm ent of their und erl yin g d ise ase
requires reduction of intravascular volume, which may
worsen their abdominal complaints. In our experience
the use of nitrates, ketanserin and alpha-inhibitors may
have a positive effect on the abdominal symptoms,
whereas calcium channel blockers seemed to worsen
these. A second group we encountered are patients
with a clinical presentation similar to CSS, with normal
microvasculature but functional tests indicating ischemia.
As discussed earlier, in some of these we have observed
vascular spasms during angiography, with onset of pain
within minutes thereafter[4]. In a pilot study, we treated
them with vasodilators, nitrates, ketanserin or nicorandil.
Over 50% of patients show a reduction of abdominal
pain of at least 50% on a visual analog scale, which is
sustained for years in most cases[52]. Further studies are
needed to assess the prevalence, precise mechanism and
the best treatment options of this disorder.
Post-intervention care
After revascularization, severe reperfusion injury can
occur. The exact risk factors for its development are
unknown. In our experience it is more common in
patients with serious and long-standing multi-vessel
disease. The following pattern in reperfusion damage
after revascularization is typical. The first 1-2 d after
revascularization the patient has good clinical recovery.
Most could start eating again without pain or special
discomfort. After 2-3 d symptoms develop, in hours
to days, consisting of nausea, abdominal pain, similar
or even worse than before treatment, diarrhea and in
extreme cases, protein-losing enteropathy with very
low serum albumin levels. Massive ascites may develop
during reperfusion.
It is crucial to distinguish reperfusion injury from
vessel occlusion; therefore vessel patency has to be
ascertained with CTA or DSA. This bowel reperfusion
syndrome can persist for days to weeks. We therefore
treat these patients with parenteral nutrition, intravenous
fluids, and proton pump inhibitors. The end of the
reperfusion syndrome is usually heralded by increased
appetite, reduced pain and reduced diarrhea. Patients
can restart oral intake, be taken off parenteral nutrition
and generally have uneventful recovery within weeks
thereafte r. No long-ter m c ompli cations have been
observed in these patients.
CONClUsION
Spl a nchn i c ische m ia has deve l oped i nto a b road
sp ectr u m of di sea ses. T hese are cha ract eri zed by
onset, vessel anatomy, and presence of ischemia. Each
syndrome has different characteristics, outcome, and
treatment options, therefore a state-of-the art vessel
anatomy assessment and accurate functional test are
crucial. Tonometry is the only validated test assessing the
adequacy of the splanchnic blood-ow and consequently
is crucial in proper patient selection. Treatment options,
including noninvasive, minimal invasive and classical
open vascular reconstructive techniques, are wide and
require a multi-disciplinary team-approach for proper
selection and follow-up.
REFERENCEs
1 Derrick JR, Pollard HS, Moore RM. The pattern of
www.wjgnet.com
Kolkman JJ
et al
. Diagnosis and management of splanchnic ischemia 7317
arteriosclerotic narrowing of the celiac and superior
mesenteric arteries. Ann Surg 1959; 149: 684-689
2 Reiner L, Jimenez FA, Rodriguez FL. Atherosclerosis in the
mesenteric circulation. observations and correlations with
aortic and coronary atherosclerosis. Am Heart J 1963; 66:
200-209
3 Kol kma n JJ, Otte JA, Groeneveld AB. Gastrointestinal
lu mi na l PC O2 ton om et ry: an upd at e on physiol og y,
methodology and clinical applications. Br J Anaesth 2000; 84:
74-86
4 Otte JA, Geelkerken RH, Oostveen E, Mensink PB,
Huisman AB, Kolkman JJ. Clinical impact of gastric exercise
tonometry on diagnosis and management of chronic
gastrointestinal ischemia. Clin Gastroenterol Hepatol 2005; 3:
660-666
5 Mensink PB, van Petersen AS, Kolkman JJ, Otte JA,
Huisman AB, Geelkerken RH. Gastric exercise tonometry:
the key investigation in patients with suspected celiac artery
compression syndrome. J Vasc Surg 2006; 44: 277-281
6 Mensink PB, van Petersen AS, Geelkerken RH, Otte JA,
Huisman AB, Kolkman JJ. Clinical signicance of splanchnic
artery stenosis. Br J Surg 2006; 93: 1377-1382
7 Ko lk ma n JJ , Mensink PB. Non-occlusive mesenteric
ischaemia: a common disorder in gastroenterology and
intensive care. Best Pract Res Clin Gastroenterol 2003; 17:
457-473
8 Bron KM, Redman HC. Splanchnic artery stenosis
and occlusion. Incidence; arteriographic and clinical
manifestations. Radiology 1969; 92: 323-328
9 Thomas JH, Blake K, Pierce GE, Hermreck AS, Seigel E. The
clinical course of asymptomatic mesenteric arterial stenosis.
J Vasc Surg 1998; 27: 840-844
10 Hansen KJ, Wilson DB, Craven TE, Pearce JD, English WP,
Edwards MS, Ayerdi J, Burke GL. Mesenteric artery disease
in the elderly. J Vasc Surg 2004; 40: 45-52
11 Valentine RJ, Martin JD, Myers SI, Rossi MB, Clagett GP.
Asymptomatic celiac and superior mesenteric artery stenoses
are more prevalent among patients with unsuspected renal
artery stenoses. J Vasc Surg 1991; 14: 195-199
12 Glockner JF. Incidental ndings on renal MR angiography.
AJR Am J Roentgenol 2007; 189: 693-700
13 Wilson DB, Mostafavi K, Craven TE, Ayerdi J, Edwards
MS, Hansen KJ. Clinical course of mesenteric artery stenosis
in elderly americans. Arch Intern Med 2006; 166: 2095-2100
14 Cho JS, Carr JA, Jacobsen G, Shepard AD, Nypaver TJ,
Reddy DJ. Long-term outcome after mesenteric artery
reconstruction: a 37-year experience. J Vasc Surg 2002; 35:
453-460
15 Lundgren O, Haglund U. The pathophysiology of the
intestinal countercurrent exchanger. Life Sci 1978; 23:
1411-1422
16 Haglund U, Hulten L, Ahren C, Lundgren O. Mucosal
lesions in the human small intestine in shock. Gut 1975; 16:
979-984
17 Schlichtig R, Bowles SA. Distinguishing between aerobic
and anaerobic appearance of dissolved CO2 in intestine
during low ow. J Appl Physiol 1994; 76: 2443-2451
18 Knichwitz G, Rotker J, Mollhoff T, Richter KD, Brussel T.
Continuous intramucosal PCO2 measurement allows the
early detection of intestinal malperfusion. Crit Care Med
1998; 26: 1550-1557
19 Otte JA, Oostveen E, Geelkerken RH, Groeneveld AB,
Kolkman JJ. Exercise induces gastric ischemia in healthy
volunteers: a tonometry study. J Appl Physiol 2001; 91:
866-871
20 Burgener D, Laesser M, Treggiari-Venzi M, Oi Y, Jolliet P,
Strasser S, Hadengue A, Aneman A. Endothelin-1 blockade
corrects mesenteric hypoperfusion in a porcine low cardiac
output model. Crit Care Med 2001; 29: 1615-1620
21 Kawano S, Tsuji S. Role of mucosal blood flow: a
conceptional review in gastric mucosal injury and protection.
J Gastroenterol Hepatol 2000; 15 Suppl: D1-D6
22 Kawano S, Tsuji S, Sato N, Kamada T. NSAIDS and the
microcirculation of the stomach. Gastroenterol Clin North Am
1996; 25: 299-315
23 Toung T, Reilly PM, Fuh KC, Ferris R, Bulkley GB.
Mesenteric vasoconstriction in response to hemorrhagic
shock. Shock 2000; 13: 267-273
24 Hamilton-Davies C, Mythen MG, Salmon JB, Jacobson D,
Shukla A, Webb AR. Comparison of commonly used clinical
indicators of hypovolaemia with gastrointestinal tonometry.
Intensive Care Med 1997; 23: 276-281
25 Heer M, Repond F, Hany A, Sulser H, Kehl O, Jager K.
Acute ischaemic colitis in a female long distance runner. Gut
1987; 28: 896-899
26 Moses FM. The effect of exercise on the gastrointestinal
tract. Sports Med 1990; 9: 159-172
27 Nielsen HB, Svendsen LB, Jensen TH, Secher NH. Exercise-
induced gastric mucosal acidosis. Med Sci Sports Exerc 1995;
27: 1003-1006
28 Veenstra RP, Geelkerken RH, Verhorst PM, Huisman AB,
Kolkman JJ. Acute stress-related gastrointestinal ischemia.
Digestion 2007; 75: 205-207
29 Wattanasirichaigoon S, Menconi MJ, Delude RL, Fink
MP. Effect of mesenteric ischemia and reperfusion or
hemorrhagic shock on intestinal mucosal permeability and
ATP content in rats. Shock 1999; 12: 127-133
30 Nielsen VG, Tan S, Baird MS, McCammon AT, Parks DA.
Gastric intramucosal pH and multiple organ injury: impact
of ischemia-reperfusion and xanthine oxidase. Crit Care Med
1996; 24: 1339-1344
31 Beuk RJ, Tangelder GJ, Maassen RL, Quaedackers JS,
Heineman E, Oude Egbrink MG. Leucocyte and platelet
adhesion in different layers of the small bowel during
experimental total warm ischaemia and reperfusion. Br J
Surg 2008; 95: 1294-1304
32 Krack A, Richartz BM, Gastmann A, Greim K, Lotze U,
Anker SD, Figulla HR. Studies on intragastric PCO2 at rest
and during exercise as a marker of intestinal perfusion in
patients with chronic heart failure. Eur J Heart Fail 2004; 6:
403-407
33 Diebel L, Kozol R, Wilson RF, Mahajan S, Abu-Hamdan D,
Thomas D. Gastric intramucosal acidosis in patients with
chronic kidney failure. Surgery 1993; 113: 520-526
34 Rogers DM, Thompson JE, Garrett WV, Talkington CM,
Patman RD. Mesenteric vascular problems. A 26-year
experience. Ann Surg 1982; 195: 554-565
35 Sitges-Serra A, Mas X, Roqueta F, Figueras J, Sanz F.
Mesenteric infarction: an analysis of 83 patients with
prognostic studies in 44 cases undergoing a massive small-
bowel resection. Br J Surg 1988; 75: 544-548
36 Kaleya RN, Sammartano RJ, Boley SJ. Aggressive approach
to acute mesenteric ischemia. Surg Clin North Am 1992; 72:
157-182
37 Bergan JJ, Dean RH, Conn J Jr, Yao JS. Revascularization
in treatment of mesenteric infarction. Ann Surg 1975; 182:
430-438
38 Jrvinen O, Laurikka J, Salenius JP, Tarkka M. Acute intestinal
ischaemia. A review of 214 cases. Ann Chir Gynaecol 1994; 83:
22-25
39 Schoots IG, Koffeman GI, Legemate DA, Levi M, van Gulik
TM. Systematic review of survival after acute mesenteric
ischaemia according to disease aetiology. Br J Surg 2004; 91:
17-27
40 Hunter GC, Guernsey JM. Mesenteric ischemia. Med Clin
North Am 1988; 72: 1091-1115
41 Otte J, Geelkerken R, Huisman A, Kolkman JJ. Assessment
of the incidence of chronic gastrointestinal ischemia
after institution of a multidisciplinary working group.
Gastroenterology 1999; 116: A915
42 Kolkman JJ, Mensink PB, van Petersen AS, Huisman AB,
Geelkerken RH. Clinical approach to chronic gastrointestinal
ischaemia: from ‚intestinal angina‘ to the spectrum of chronic
splanchnic disease. Scand J Gastroenterol Suppl 2004; 9-16
7318 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol December 28, 2008 Volume 14 Number 48
www.wjgnet.com
43 Brandt LJ, Boley SJ. AGA technical review on intestinal
ischemia. American Gastrointestinal Association. Gastroen-
terology 2000; 118: 954-968
44 Szilagyi DE, Rian RL, Elliott JP, Smith RF. The cardiac
artery compression syndrome: does it exist? Surgery 1972;
72: 849-863
45 Kernohan RM, Barros D’Sa AA, Cranley B, Johnston
HM. Further evidence supporting the existence of the
celiac artery compression syndrome. Arch Surg 1985; 120:
1072-1076
46 Reilly LM, Ammar AD, Stoney RJ, Ehrenfeld WK.
Late results following operative repair for celiac artery
compression syndrome. J Vasc Surg 1985; 2: 79-91
47 Loffeld RJ, Overtoom HA, Rauwerda JA. The celiac axis
compression syndrome. Report of 5 cases. Digestion 1995;
56: 534-537
48 Brandt LJ, Boley SJ. Colonic ischemia. Surg Clin North Am
1992; 72: 203-229
49 Koutroubakis IE, Sfiridaki A, Theodoropoulou A,
Kouroumalis EA. Role of acquired and hereditary thrombotic
risk factors in colon ischemia of ambulatory patients.
Gastroenterology 2001; 121: 561-565
50 Sotiriadis J, Brandt LJ, Behin DS, Southern WN. Ischemic
colitis has a worse prognosis when isolated to the right side
of the colon. Am J Gastroenterol 2007; 102: 2247-2252
51 Mythen MG, Purdy G, Mackie IJ, McNally T, Webb AR,
Machin SJ. Postoperative multiple organ dysfunction
syndrome associated with gut mucosal hypoperfusion,
increased neutrophil degranulation and C1-esterase inhibitor
depletion. Br J Anaesth 1993; 71: 858-863
52 Kolkman JJ, Mensink PBF, Huisman AB, Kuipers E,
Geelkerken RH. Gastric ischemic pain with normal mesenteric
vessels: A new disease entity? Report on diagnosis, treatment
and outcome in 14 patients. Gastroenterology 2004; 126: A254
53 Moneta GL, Lee RW, Yeager RA, Taylor LM Jr, Porter JM.
Mesenteric duplex scanning: a blinded prospective study. J
Vasc Surg 1993; 17: 79-84; discussion 85-86
54 Burkart DJ, Johnson CD, Reading CC, Ehman RL. MR
measurements of mesenteric venous flow: prospective
evaluation in healthy volunteers and patients with suspected
chronic mesenteric ischemia. Radiology 1995; 194: 801-806
55 Szinnai C, Mottet C, Gutzwiller JP, Drewe J, Beglinger C,
Sieber CC. Role of gender upon basal and postprandial
systemic and splanchnic haemodynamics in humans. Scand
J Gastroenterol 2001; 36: 540-544
56 Lycklama a Nijeholt GJ, Burggraaf K, Wasser MN, Schultze
Kool LJ, Schoemaker RC, Cohen AF, de Roos A. Variability
of splanchnic blood ow measurements using MR velocity
mapping under fasting and post-prandial conditions--
comparison with echo-Doppler. J Hepatol 1997; 26: 298-304
57 Hoost U, Kelbaek H, Rasmusen H, Court-Payen M,
Christensen NJ, Pedersen-Bjergaard U, Lorenzen T. Haemo-
dynamic effects of eating: the role of meal composition. Clin
Sci (Lond) 1996; 90: 269-276
58 Tsukuda T, Ito K, Koike S, Sasaki K, Shimizu A, Fujita T,
Miyazaki M, Kanazawa H, Jo C, Matsunaga N. Pre- and
postprandial alterations of portal venous flow: evaluation
with single breath-hold three-dimensional half-Fourier fast
spin-echo MR imaging and a selective inversion recovery
tagging pulse. J Magn Reson Imaging 2005; 22: 527-533
59 Liem TK, Segall JA, Wei W, Landry GJ, Taylor LM,
Moneta GL. Duplex scan characteristics of bypass grafts to
mesenteric arteries. J Vasc Surg 2007; 45: 922-927; discussion
927-928
60 Billaud Y, Beuf O, Desjeux G, Valette PJ, Pilleul F. 3D
contrast-enhanced MR angiography of the abdominal
aorta and its distal branches: Interobserver agreement of
radiologists in a routine examination. Acad Radiol 2005; 12:
155-163
61 Holland GA, Dougherty L, Carpenter JP, Golden MA,
Gilfeather M, Slossman F, Schnall MD, Axel L. Breath-
hold ultrafast three-dimensional gadolinium-enhanced MR
angiography of the aorta and the renal and other visceral
abdominal arteries. AJR Am J Roentgenol 1996; 166: 971-981
62 Meaney JF, Prince MR, Nostrant TT, Stanley JC.
Gadolinium-enhanced MR angiography of visceral arteries
in patients with suspected chronic mesenteric ischemia. J
Magn Reson Imaging 1997; 7: 171-176
63 Prince MR, Narasimham DL, Stanley JC, Chenevert TL,
Williams DM, Marx MV, Cho KJ. Breath-hold gadolinium-
enhanced MR angiography of the abdominal aorta and its
major branches. Radiology 1995; 197: 785-792
64 Mensink PBF, Kolkman JJ, Geelkerken RH, van Petersen
AS, Rozeboom AR, Huisman AB. Comparison of magnetic
resonance angiography and conventional angiography
of the mesenteric arteries in patients suspected of chronic
mesenteric ischemia. Gastroenterology 2004; 126: A96
65 Burkart DJ, Johnson CD, Ehman RL. Correlation of arterial
and venous blood ow in the mesenteric system based on
MR ndings. 1993 ARRS Executive Council Award. AJR Am
J Roentgenol 1993; 161: 1279-1282
66 Applegate GR, Thaete FL, Meyers SP, Davis PL, Talagala SL,
Recht M, Wozney P, Kanal E. Blood ow in the portal vein:
velocity quantitation with phase-contrast MR angiography.
Radiology 1993; 187: 253-256
67 Iannaccone R, Laghi A, Passariello R. Multislice CT
angiography of mesenteric vessels. Abdom Imaging 2004; 29:
146-152
68 Horton KM, Fishman EK. Multidetector CT angiography in
the diagnosis of mesenteric ischemia. Radiol Clin North Am
2007; 45: 275-288
69 Savastano S, Teso S, Corra S, Fantozzi O, Miotto D. Multislice
CT angiography of the celiac and superior mesenteric
arteries: comparison with arteriographic ndings. Radiol Med
2002; 103: 456-463
70 Ilica AT, Kocaoglu M, Bilici A, Ors F, Bukte Y, Senol A,
Ucoz T, Somuncu I. Median arcuate ligament syndrome:
multidetector computed tomography findings. J Comput
Assist Tomogr 2007; 31: 728-731
71 Stueckle CA, Haegele KF, Jendreck M, Zipser MC, Kirchner
J, Kickuth R, Liermann D. Multislice computed tomography
angiography of the abdominal arteries: comparison between
computed tomography angiography and digital subtraction
angiography ndings in 52 cases. Australas Radiol 2004; 48:
142-147
72 Laghi A, Catalano C, Iannaccone R, Paolantonio P,
Panebianco V, Sansoni I, Trenna S, Passariello R. [Multislice
spiral CT angiography in the evaluation of the anatomy of
splanchnic vessels: preliminary experience] Radiol Med 2001;
102: 127-131
73 Kozuch PL, Brandt LJ. Review article: diagnosis and
management of mesenteric ischaemia with an emphasis on
pharmacotherapy. Aliment Pharmacol Ther 2005; 21: 201-215
74 Habu Y, Tahashi Y, Kiyota K, Matsumura K, Hirota M,
Inokuchi H, Kawai K. Reevaluation of clinical features of
ischemic colitis. Analysis of 68 consecutive cases diagnosed
by early colonoscopy. Scand J Gastroenterol 1996; 31: 881-886
75 Lar so n MV, Ahlquist DA, Karlstrom L, Sarr MG.
Intraluminal measurement of enteric mucosal perfusion:
relationship to superior mesenteric artery flow during
basal and postprandial states in the dog. Surgery 1994; 115:
118-126
76 Friedland S, Benaron D, Coogan S, Sze DY, Soetikno R.
Diagnosis of chronic mesenteric ischemia by visible light
spectroscopy during endoscopy. Gastrointest Endosc 2007;
65: 294-300
77 Tollefson DF, Wright DJ, Reddy DJ, Kintanar EB.
Intraoperative determination of intestinal viability by pulse
oximetry. Ann Vasc Surg 1995; 9: 357-360
78 Avino AJ, Oldenburg WA, Gloviczki P, Miller VM, Burgart
LJ, Atkinson EJ. Inferior mesenteric venous sampling to
detect colonic ischemia: a comparison with laser Doppler
owmetry and photoplethysmography. J Vasc Surg 1995; 22:
271-277; discussion 278-279
www.wjgnet.com
Kolkman JJ
et al
. Diagnosis and management of splanchnic ischemia 7319
79 MacDonald PH, Dinda PK, Beck IT, Mercer CD. The use of
oximetry in determining intestinal blood ow. Surg Gynecol
Obstet 1993; 176: 451-458
80 Vahl AC, van Rij GL, Visser JJ, Nauta SH, Vink GQ,
Scheffer GJ, de Lange-de Klerk ES, Uyterlinde A, Brom HL,
Rauwerda JA. Endoluminal pulse oximetry in ischemic
colon in a swine model. J Am Coll Surg 1995; 180: 57-64
81 Boley SJ, Brandt LJ, Veith FJ, Kosches D, Sales C. A new
provocative test for chronic mesenteric ischemia. Am J
Gastroenterol 1991; 86: 888-891
82 Geelkerken RH, Schultze Kool LJ, Hermans J, Zarza MT,
van Bockel JH. Chronic splanchnic ischaemia: is tonometry
a useful test? Eur J Surg 1997; 163: 115-121
83 Fiddian-Green RG. Provocative test for chronic mesenteric
ischemia. Am J Gastroenterol 1992; 87: 543
84 Kolkman JJ, Groeneveld AB, Meuwissen SG. Effect of
gastric feeding on intragastric P(CO2) tonometry in healthy
volunteers. J Crit Care 1999; 14: 34-38
85 Mensink PB, Geelkerken RH, Huisman AB, Kuipers EJ,
Kolkman JJ. Effect of various test meals on gastric and
jejunal carbon dioxide: A study in healthy subjects. Scand J
Gastroenterol 2006; 41: 1290-1298
86 Mensink PB, Geelkerken RH, Huisman AB, Kuipers EJ,
Kolkman JJ. Twenty-four hour tonometry in patients
suspected of chronic gastrointestinal ischemia. Dig Dis Sci
2008; 53: 133-139
87 Veenstra R, Mensink P, Huisman A, Geelkerken B,
Kolkman J. The value of jejunal exercise tonometry for the
diagnosis of chronic gastrointestinal ischemia. Comparison
of jejunal with gastric exercise tonometry in 100 patients
suspected of GI ischemia. Gastroenterology 2007; 132: A369
88 Ockner RK, Manning JA. Fatty acid-binding protein in
small intestine. Identification, isolation, and evidence for
its role in cellular fatty acid transport. J Clin Invest 1974; 54:
326-338
89 Lieberman JM, Sacchettini J, Marks C, Marks WH. Human
intestinal fatty acid binding protein: report of an assay
with studies in normal volunteers and intestinal ischemia.
Surgery 1997; 121: 335-342
90 Pelsers MM, Namiot Z, Kisielewski W, Namiot A,
Januszkiewicz M, Hermens WT, Glatz JF. Intestinal-type
and liver-type fatty acid-binding protein in the intestine.
Tissue distribution and clinical utility. Clin Biochem 2003; 36:
529-535
91 Gollin G, Zieg PM, Cohn SM, Lieberman JM, Marks WH.
Intestinal mucosal injury in critically ill surgical patients:
preliminary observations. Am Surg 1999; 65: 19-21
92 Rahman SH, Ammori BJ, Holmeld J, Larvin M, McMahon
MJ. Intestinal hypoperfusion contributes to gut barrier
failure in severe acute pancreatitis. J Gastrointest Surg 2003;
7: 26-35; discussion 35-36
93 Wiercinska-Drapalo A, Jaroszewicz J, Siwak E, Pogorzelska
J, Prokopowicz D. Intestinal fatty acid binding protein
(I-FABP) as a possible biomarker of ileitis in patients with
ulcerative colitis. Regul Pept 2008; 147: 25-28
94 Hol L, Mensink PB, Borghuis-Koertshuis N, Geelkerken
R, Huisman AB, Doelman CJ, Kusters JG, Kuipers EJ,
Kolkman JJ. Transient postprandial ischemia, detected
with tonometry, is associated with increased I-FABP in
patients with chronic GI-ischemia (“abdominal angina”).
Gastroenterology 2005; 128: A656
95 Atkins MD, Kwolek CJ, LaMuraglia GM, Brewster DC,
Chung TK, Cambria RP. Surgical revascularization versus
endovascular therapy for chronic mesenteric ischemia: a
comparative experience. J Vasc Surg 2007; 45: 1162-1171
96 Biebl M, Oldenburg WA, Paz-Fumagalli R, McKinney
JM, Hakaim AG. Surgical and interventional visceral
revascularization for the treatment of chronic mesenteric
ischemia--when to prefer which? World J Surg 2007; 31 :
562-568
97 Sarac TP, Altinel O, Kashyap V, Bena J, Lyden S, Sruvastava
S, Eagleton M, Clair D. Endovascular treatment of stenotic
and occluded visceral arteries for chronic mesenteric
ischemia. J Vasc Surg 2008; 47: 485-491
98 van Bockel JH, Geelkerken RH, Wasser MN. Chronic
splanchnic ischaemia. Best Pract Res Clin Gastroenterol 2001;
15: 99-119
99 Moyes LH, McCarter DH, Vass DG, Orr DJ. Intraoperative
retrograde mesenteric angioplasty for acute occlusive
mesenteric ischaemia: a case series. Eur J Vasc Endovasc Surg
2008; 36: 203-206
100 Wyers MC, Powell RJ, Nolan BW, Cronenwett JL.
Retrograde mesenteric stenting during laparotomy for acute
occlusive mesenteric ischemia. J Vasc Surg 2007; 45: 269-275
101 Cohn I Jr, Floyd CE, Dresden CF, Bornside GH. Strangulation
obstruction in germfree animals. Ann Surg 1962; 156: 692-702
102 Longo WE, Ballantyne GH, Gusberg RJ. Ischemic colitis:
patterns and prognosis. Dis Colon Rectum 1992; 35: 726-730
103 van Petersen AS, Vriens BHR, Huisman AB, Kolkman JJ,
Geelkerken RH. A new minimally invasive treatment for
the celiac artery compression syndrome: retroperitoneal
endoscopic release; experience in 46 patients. submitted
104 Hinder RA, Fimmel CJ, Rickards E, von Ritter C, Svensson
LG, Blum AL. Stimulation of gastric acid secretion increases
mucosal blood ow in immediate vicinity of parietal cells in
baboons. Dig Dis Sci 1988; 33: 545-551
S- Editor Tian L L- Editor Stewart GJ E- Editor Ma WH
7320 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol December 28, 2008 Volume 14 Number 48
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