ORIGINAl PAPERS - Advances in Clinical and Experimental Medicine

ORIGINAl PAPERS - Advances in Clinical and Experimental Medicine

orIginal papers
Adv Clin Exp Med 2011, 20, 5, 613–621
ISSN 1230-025X
© Copyright by Wroclaw Medical University
Ayten Saracoglu1, Kemal T. Saracoglu1, Mustafa Deniz2, Feriha Ercan3,
Yunus Yavuz4, Yılmaz Gogus1
Dopamine – a Preventive Agent for Mesenteric Ischemia
and Reperfusion Injury in Abdominal
Compartment Syndrome
Dopamina – czynnik ochronny przed niedokrwieniem krezki
i uszkodzeniem reperfuzyjnym w zespole ciasnoty śródbrzusznej
Department of Anesthesiology and Reanimation, Marmara University School of Medicine, Istanbul, Turkey
Department of Physiology, Onsekiz Mart University School of Medicine, Canakkale, Turkey
3
Department of Histology and Embriology, Marmara University School of Medicine, Istanbul, Turkey
4
Department of General Surgery, Marmara University School of Medicine, Istanbul, Turkey
1
2
Abstract
Objectives. Acutely increased intra-abdominal pressure (IAP) may lead to abdominal compartment syndrome
(ACS) and multiple organ failure. In a prospective randomized way, the effect of dopamine infusion (3 μg/kg/
min) on mesenteric perfusion, cytokine levels and intestinal histopathological changes were studied in the presence of ACS.
Material and Methods. The study involved 28 male Sprague Dawley rats randomly assigned to four groups
(n = 7). The external jugular vein was cannulated for infusions. In group 1, before increasing IAP, a 60-minute
infusion of dopamine was performed; following this, IAP was raised and the dopamine infusion was continued
for another 60 minutes. In group 2 an IAP of 20 mm Hg was maintained for 60 minutes by air insufflation. In
group 3, a dopamine infusion was performed simultaneously with an IAP of 20 mm Hg for 60 minutes. Group
4 was the control. Following this phase, midline laparatomy and superior mesenteric artery (SMA) dissection was
carried out in all groups and SMA perfusion was measured continuously for 30 minutes with a Doppler probe.
Myeloperoxidase (MPO) activity, lipid peroxidation and glutathione (GSH) levels were measured in tissue samples
and histopathological scoring was carried out.
Results. The results demonstrated that SMA blood flow was increased in Group 1 and Group 3 (100.77 ± 2.94 and
93.82 ± 4.91 mm Hg, respectively) but decreased significantly in Group 2 (74.23 ± 3.01 mm Hg; p < 0.01). Intestinal
tissue malondialdehyde (MDA) levels (24.03 ± 2.75 nmol/g) and MPO activity (260.5 ± 11 u/g) were elevated in
Group 2; histological scores were elevated in all groups (p < 0.05); and GSH levels were reduced in Group 2 (0.58
± 0.24 µmol/g; p < 0.01).
Conclusions. The results indicated that high IAP causes oxidative organ damage and that dopamine may lessen
reperfusion-induced oxidative damage by reducing splanchnic perfusion and controlling the reperfusion of the
intra-abdominal organs (Adv Clin Exp Med 2011, 20, 5, 613–621).
Key words: abdominal compartment syndrome, ischemia/reperfusion, superior mesenteric artery, blood flow,
dopamine.
Streszczenie
Cel pracy. Bardzo podwyższone ciśnienie śródbrzuszne (IAP) może prowadzić do zespołu ciasnoty śródbrzusznej (ACS) i niewydolności wielonarządowej. W prospektywnym randomizowanym badaniu oceniono
wpływ wlewu dopaminy (3 μg/kg/min) na perfuzję krezki, stężenie cytokin i histopatologiczne uszkodzenia
jelit w obecności ACS.
Materiał i metody. Do badań włączono 28 samców szczurów Sprague Dawley, które przydzielono losowo do czterech grup (n = 7). Przez zewnętrzną żyłę szyjną wprowadzono kaniulę do infuzji. W grupie 1 przed zwiększeniem
IAP przeprowadzono 60-minutową infuzję dopaminy, potem zwiększono IAP i kontynuowano wlew dopaminy
przez kolejne 60 min. W grupie 2 IAP utrzymywano 20 mm Hg IAP przez 60 min za pomocą wdmuchiwania
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powietrza. W grupie 3 wlew dopaminy był prowadzony jednocześnie z 20 mm Hg IAP przez 60 min. Grupa 4 była
kontrolna. Po tej fazie wykonano laparatomię w linii środkowej i wycięcie tętnicy krezkowej górnej (SMA) we
wszystkich grupach. Za pomocą sondy Dopplera zmierzono perfuzję SMA w sposób ciągły przez 30 min. Oceniono
aktywność mieloperoksydazy (MPO), peroksydację lipidów oraz stężenie glutationu (GSH) w próbkach tkanek
i nadano histopatologiczną punktację.
Wyniki. Badanie wykazało, że przepływ krwi przez SMA był zwiększony w grupie 1 i grupie 3 (100,77 ± 2,94 i 93,82
± 4,91 mm Hg), ale zmniejszył się znacząco w grupie 2 (74,23 ± 3,01 mm Hg, p < 0,01). Stężenie malondialdehydu
(MDA) (24,03 ± 2,75 nmol/g) i aktywność MPO (260,5 ± 11 U/g) były zwiększone w tkankach jelit w grupie 2;
histologiczna punktacja była większa w wszystkich grupach (p < 0,05), a stężenie GSH zmniejszyło się w grupie 2
(0,58 ± 0,24 mmol/g, p < 0,01).
Wnioski. Badania wykazały, że duże IAP powoduje oksydacyjne uszkodzenie narządów i że dopamina może zmniejszyć uszkodzenie oksydacyjne wywołane przez reperfuzję, ograniczając perfuzję trzewną i reperfuzję narządów jamy
brzusznej (Adv Clin Exp Med 2011, 20, 5, 613–621).
Słowa kluczowe: zespół ciasnoty śródbrzusznej, niedokrwienie/reperfuzja, tętnica krezkowa górna, przepływ krwi,
dopamina.
Intra-abdominal pressure (IAP) can be acutely
increased by a variety of causes, including major
trauma or abdominal surgery [1]. Pathophysiological changes begin when IAP reaches levels higher
than 8 mm Hg [2]. When IAP reaches a critical level
(above approximately 15 mm Hg) it can cause fatal
multiple organ failure, known as ACS [3]. When it
reaches 20 mm Hg, mesenteric blood flow decreases
to 70% of its basal value; at 40 mm Hg, blood flow
decreases to 30% of normal [4]. The detrimental
effects of raised IAP and ACS on the cardiac, pulmonary, hepatic and renal systems are well known
and easy to detect clinically [5]. High venous resistance plays a major role in the pathogenesis of ACS
[6]. Early abdominal decompression has beneficial
results for organ dysfunction and can improve survival in critically ill patients, but it can also cause additional ischemia-reperfusion (I/R) injury and seriously increase morbidity. As Kaçmaz et al. pointed
out, reperfusion of ischemic tissue has harmful effects on cellular functions by activating the various
reactive oxygen metabolites [7]. Free oxygen radicals are formed by lipid peroxidation and cause the
destruction of cell membranes. Various chemicals
and I/R injury produce reactive oxygen radicals and
these products promote microvascular disturbances
[8]. Polymorphonuclear leukocyte infiltration activates chemotactic mediators in tissue and results in
acute inflammation [9].
Antioxidant compounds contribute to protecting cells and tissues against the harmful effects of
I/R injury [10, 11]. Low-dose dopamine acts as an
inotropic agent and also augments superior mesenteric artery (SMA) blood flow [12]. Dopamine
has a dose-dependent effect on several specific
receptors, producing a pharmacological response
[13]. Low-dose dopamine infusion (3 to 5 μg/kg/
/min) activates β1- and β2-adrenergic receptors.
This experimental study was undertaken to determine the effects of low-dose dopamine infusion
on intestinal blood flow and in the prevention and
treatment of I/R injury.
Material and Methods
The Animals
The experiment was carried out on 28 male
Sprague Dawley rats (200–250 g) randomly assigned
to four groups (n = 7). All experimental protocols
were approved by the Marmara University School
of Medicine Animal Care and Use Committee.
The animals were housed in an air-conditioned room with 12-hour light/dark cycles, where
the temperature (22 ± 2°C) and relative humidity
(65–70%) were kept constant. The animals were
fasted overnight; then, under 1.2 g/kg intraperitoneal urathane anesthesia, tracheotomies were performed to facilitate breathing. The right carotid
artery was cannulated to record arterial pressure
(using a Nihon Kohden polygraph, model AP-621G). The right jugular vein was also cannulated
for the injection of saline or dopamine. A thermometer was inserted into the rectum and the
body temperature was maintained at 37°C with
a heating pad. A 24 g polymer catheter (0.7 mm
× 14 mm) was then inserted intraperioneally. In
Groups 1, 2 and 3, using an aneroid sphygmomanometer connected to the catheter, IAP was increased until the aneroid gauge measured 20 mm
Hg, and the pressure was maintained for one hour
to induce ACS. The animals in Group 1 received
a 3 μg/kg/min dopamine infusion both before and
during the procedure; Group 2 received a saline
solution during the procedure; Group 3 received
a dopamine infusion during the procedure. The
control group (Group 4) had normal IAP. After
inducing ACS, surgical decompression of the abdomen and measurement of SMA blood flow were
performed for 30 minutes. At the end of the blood
flow measurement, the rats were decapitated. Small
intestine (jejunum) tissue samples were removed
for the determination of tissue MDA, GSH and
MPO levels. Histological damage was scored using
the criteria of Ho-Lam Chung et al. [14], which as-
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Dopamine in Abdominal Compartment Syndrome
sess the inflammatory infiltrate (maximum score
= 3) and tissue damage (maximum score = 3).
Blood Flow Measurements
SMA blood flow was measured using the ultrasonic transit time technique [15]. A 0.7 VB 156
probe (Transonics Systems, Ithaca, NY) was used.
The probe has two ultrasonic transducers and
a fixed acoustic reflector. A 5 mm section of the
SMA was isolated for flow probe placement. All
fatty tissue was removed from the isolated segment
of the vessel to avoid obstruction of the ultrasonic
signal. A flow meter (Transonic Systems, model
T106) was used to estimate the volume of blood
flow, which is expressed in milliliters per minute
per 100 g of tissue. Mean arterial pressure (MAP)
was recorded simultaneously through a catheter
inserted into the carotid artery (Nihon Kohden
multichannel recorder, model AP-621G). The resistance of the renal artery (expressed as mm Hg/
/ml/min/100 g) was calculated by dividing the MAP
(in millimeters of mercury) by the blood flow.
Myeloperoxidase Activity
The tissue samples were stored at –80°C for
subsequent measurement of myeloperoxidase activity (MPO). The tissue samples were homogenized in 10 cc of ice-cold potassium phosphate
buffer (20 mM K2HPO4, pH 6,0). The homogenate
was centrifuged at 12,000 rpm for 10 minutes at
4°C, and the supernatant was discarded. The pellet
was then rehomogenized with an equivalent volume of 50 mM K2HPO4 containing 0.5% hexadecyltrimethylammonium hydroxide. MPO activity
was assessed by measuring the H2O2-dependent
oxidation of o-dianisidine 2HCl. One unit of enzyme activity is defined as the amount of MPO
that causes a change in absorbance of 1.0/min at
460 nm and 37°C [16].
Malondialdehyde
and Glutathione Assays
Tissue samples were homogenized in 10 cc of
ice-cold 10% trichloracetic acid and centrifuged at
3000 rpm for 15 minutes at 4°C. The supernatant
was removed and recentrifuged at 10,000 rpm at
4°C for 8 minutes. The supernatant was transferred to a test tube containing an equal volume of
0.67% TBA; this mixture was then heated to 90°C
and maintained at that temperature for 15 minutes. The MDA concentration for each specimen
was determined in a spectrophotometer based on
the level of absorbance at 532 nm, and was ex-
pressed as nmol/g tissue [17]. GSH measurements
were performed using a modification of the Ellman procedure [18]. Briefly, after centrifugation at
3000 rpm for 10 minutes, 0.5 ml of the supernatant
was added to 2 ml of 0.3 mol/l Na2HPO4 2H2O solution. A 0.2 ml solution of dithiobisnitrobenzoate
(0.4 mg/ml, 1% sodium citrate) was added and the
absorbance at 412 nm was measured immediately
after mixing. GSH levels were calculated using an
extinction coefficient of 1.36 × 105 M/cm. The results were expressed in µmol GSH/g tissue.
Histological Analysis
For light microscopic investigations, intestinal tissues were fixed in 10% formaldehyde, dehydrated in increasing alcohol series, cleared in toluene and embedding in paraffin. Paraffin sections
(5 µm) were stained with hematoxylin and eosin
(H&E) and examined under a photomicroscope
(Olympus BX51, Tokyo, Japan) by an experienced
histologist for “blind” characterization of histopathological changes.
Statistics
All values are presented as means ± SE. Groups
of data were compared with using ANOVA followed
by Tukey’s multiple comparison test. Differences
were considered statistically significant if p < 0.05.
Results
Blood Flow and Resistance
Intestinal artery blood flow values were significantly lower in the groups with ACS than in the
control group (p < 0.01, Fig. 1a). The blood flow
was significantly improved by dopamine in both
Group 1 and Group 3 (p < 0.01). Similar results
were noted in the vascular resistance data (Fig. 1b),
in which SMA resistance was significantly normalized by dopamine infusion.
In the saline-treated ACS group (Group 2)
there was no significant change in MAP compared
to the control group (Table 1). The MAP was
100.77 ± 2.94 mm Hg in Group 1, 74.23 ± 3 mm
Hg in Group 2, 93.82 ± 4.91 mm Hg in Group
3 and 87.5 ± 10.32 mm Hg in the control group.
Myeloperoxidase Activity
MPO activity, which is accepted as an indicator of neutrophil infiltration, was significantly elevated in the small intestines of Group 2 animals:
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A. Saracoglu et al.
Fig. 1. Changes in a) superior mesenteric
artery blood flow and b) resistance.
Values are mean: *p < 0.05, **p < 0.01
Ryc. 1. Zmiany w a) przepływie krwi
przez tętnicę krezkową górną i b) oporze
naczyniowym. Wartości średnie:
* p < 0,05; ** p < 0,01
Table 1. Mean arterial pressure
Tabela 1. Średnie ciśnienie tętnicze
MAP (mm Hg)
Group 1* (Grupa 1 )
Group 2 (Grupa 2)
Group 3* (Grupa 3)
Group 4 (Grupa 4)
100.77 ± 2.94
74.23 ± 3.01
93.82 ± 4.91
87.5 ± 10.32
* p < 0.05 compared with the control group.
* p < 0,05 w porównaniu z grupą kontrolną.
260.5 ± 11 U/g, as compared to 172.9 ± 8.85 U/g
in the control group (p < 0.001; Fig. 2a). Treatment with dopamine reversed these elevations in
the intestinal tissue: The MPO activity in Group
1 was 174.9 ± 10.83 and in Group 3 it was 11.43
± 15.88.
Malondialdehyde Levels
MDA levels, an index of lipid peroxidation,
were significantly elevated in the intestinal tissue
(24.038 ± 2.75 nmol/g) in Group 2, as compared
to 17.53 ± 0.89 nmol/g in the control group (p <
< 0.05). Dopamine treatment significantly decreased
the ACS induced elevation in intestinal MDA levels (Group 1: 17.37 ± 1.78 nmol/g; Group 3: 15.37
± 2 nmol/g; p < 0.05; Fig. 2b).
Glutathione Levels
GSH levels in intestinal tissue decreased significantly when IAP was elevated in Group 2 (0.58
± 0.24 μmol/g) as compared to the control group
(1.29 ± 0.09 μmol/g) (p < 0.001). Dopamine treatment significantly preserved GSH levels (Group 1:
1.35 ± 0.13; Group 3: 0.95 ± 0.03 μmol/g; p < 0.01
and p < 0.001 respectively, compared to Group 2;
Fig. 2c).
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Dopamine in Abdominal Compartment Syndrome
Fig. 2. a) Myeloperoxidase activity,
b) malondialdehyde level and c) glutathione level in the small intestine:
*p < 0.05, **p < 0.01
Ryc. 2. a) Aktywność mieloperoksydazy,
b) stężenie malondialdehydu
i c) glutationu w jelicie cienkim:
*p < 0,05; **p < 0,01
Histological Score
Light microscopic evaluation revealed that
the ACS-induced microscopic damage score in
intestinal tissues was very high (2.97 ± 0.028) in
comparison with the control tissue (1.023 ± 0.1;
p < 0,001; Fig. 3). However, in the dopaminetreated ACS groups the scores were significantly
lower than in the saline-treated ACS group (1.97
± 0.26 in Group 1 and 1.49 ± 0.13 in Group 3; p <
< 0.001 and p < 0.01, respectively). Regular intestinal morphology with orderly villus and glands
was observed in light microscopic evaluation of
the control group (Fig. 4a). In Group 2, severe
vascular congestion, spilled epithelium, damaged
glands with severe inflammatory cell infiltration,
leukocytes and vasocongestion were observed
(Fig. 4b–c). On the other hand, the morphologically demonstrated degeneration of the intestinal
tissues of the rats was clearly improved when the
animals were treated with dopamine infusion.
Improved epithelium and improved glandular
construction were observed in Group 1 (Fig. 4d).
Regular epithelial structure, reduced edema of the
lamina propria and improved glandular structure
were observed in Group 3 (Fig. 5).
Discussion
In the pathophysiology of ACS, oxidative
tissue injury has an important role, through increased lipid peroxidation and decreased levels of
GSH [19]. MPO activity and small intestinal blood
flow are also indicators. Paralleling Şener et al.’s
results with melatonin [19], the current study indicated that dopamine protects against the oxida-
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Fig. 3. Microscopic damage scores in
the small intestine. ***p < 0.01,
**p < 0.01 compared with the control
group; +++p < 0.01 ++p < 0.01 compared with group 2
Ryc. 3. Mikroskopowa ocena
uszkodzeń w jelicie cienkim. ***p
< 0,01; **p < 0,01 w porównaniu
z grupą kontrolną +++p < 0,01
+ +p < 0,01 w porównaniu z grupą 2
Fig. 4. a) Intestinal tissue sample from the control group. Orderly villus (arrows) and glandular tissue (*), HE, × 100
magnification; b) intestinal tissue sample from group 2; spilled epithelium (arrows) and damaged gland (*), HE, × 100
magnification; c) ACS without dopamine treatment; cell increments after intense epithelium spilling (**), damaged
epithelium (arrows), leukocytes (arrowhead) vasocongestion (v) HE, × 200 and × 400 magnification; d) intestinal
tissue sample from group 1: improved epithelium (arrow), improved glandular structure (*), occasional leukocytes
(arrow in inset), HE, × 100 and × 400 magnification
Ryc. 4. a) Próbki tkanki jelit z grupy kontrolnej; kosmki (strzałki) i tkanka gruczołowa (*), HE, powiększenie 100 ×;
b) próbki tkanki jelit z grupy 2; rozlany nabłonek (strzałki) i uszkodzony gruczoł (*), HE, powiększenie 100 ×; c) ACS
bez leczenia dopaminą; odstępy między komórkami po intensywnym rozlaniu nabłonka (**), uszkodzony nabłonek
(strzałki), leukocyty (strzałki) przekrwienie (v) HE, powiększenie 200 × i 400 ×; d) próbki tkanki jelit z grupy 1:
prawidłowy nabłonek (strzałka), poprawa struktury gruczołowej (*), sporadyczne leukocyty (strzałka we wstawce),
HE, powiększenie 100 × i 400 ×
tive injury caused by ACS. In addition, impaired
intestinal blood flow was ameliorated by treatment
with low-dose dopamine before and/or during the
induction of ACS.
IAP can be acutely increased by a variety of
causes: major trauma, abdominal surgery, tense
ascites, abdominal hemorrhage, intestinal obstruction, large abdominal tumors, peritoneal dialysis, gas insufflation during laparoscopic surgery
[20, 21]. Normal IAP for healthy adults is between
0 and 5 mm Hg; it changes from 5 to 7 mm Hg for
critically ill patients. Pathological changes in cell
components begin when IAP rises above 8 mm
Hg. The World Society of Abdominal Compartment Syndrome (WSACS) defines intra-abdominal hypertension (IAH) as sustained or repeated
pathologic elevation of IAP greater than 12 mm
Hg [22, 23].
High IAP levels reduce the blood flow to all
abdominal viscera, but the adrenal glands seem to
be protected in experimental studies [24]. This effect is related to venous occlusion in the mesenteric
Dopamine in Abdominal Compartment Syndrome
Fig. 5. Intestinal tissue sample from Group 3. Regular
epithelial structure (arrow), reduced edema of the
lamina propria (*), improved intestinal villi structure
(* in inset) and occasional leukocytes (arrow in inset),
HE, × 200 and × 400 magnification
Ryc. 5. Próbki tkanki jelit z grupy 3. Typowa struktura
nabłonka (strzałka), zmniejszenie obrzęków blaszki
właściwej (*), poprawa struktury kosmków jelitowych (* we wstawce) i sporadyczne leukocyty (strzałka
we wstawce), HE, powiększenie 200 × i 400 ×
region, so that bowel wall edema occurs and IAH
becomes more aggravated [25]. Severe intestinal
ischemia has a destructive effect on the function
and structure of the cardiovascular, pulmonary
and renal systems [26]. Barnes et al. [27] demonstrated that as IAP was increased to 40 mm Hg,
there was a 36% reduction in cardiac output,
with even greater reductions in blood flow in the
celiac artery (42%), superior mesenteric artery
(61%) and renal arteries (70%). Similarly, Diebel
et al. [28] reported that IAH significantly reduces
blood flow in the hepatic artery, mesenteric artery
and portal vein, and finally causes severe intestinal ischemia, without any change in MAP or cardiac output. A continuous IAP of 20 mm Hg for
one hour was found to be the cause of intestinal
barrier dysfunction and bacterial translocation in
rats [29]. The translocation of bacteria and toxins
through the intestinal mucosa causes systemic inflammation and leads to death via multiple organ
failure syndrome and in critically ill patients [30].
Treating IAP with decompression may also cause
serious problems like I/R injury. Intestinal damage
increases further during reperfusion due to an increase in reactive oxygen radicals and endogenous
antioxidant defense mechanisms [31].
Dopamine stimulates dopamineric (D1 and
D2) and adrenergic (α and β) receptors. It facilitates direct vasodilation by D2 receptor activation.
The effects via dopaminergic α and β receptors
are dose-dependent and reflect the pharmacology of low-dose dopamine [32] Stimulation of the
β-receptor may result in increased cardiac output,
619
whereas stimulation of the α-receptor may increase perfusion pressure by activation of D1 and
D2 receptors [33]. At doses of 3 μg/kg/min, dopamine has been found to activate D1 receptors,
which causes vasodilation [34]. Dopamine infusions of 3 to 5 μg/kg/min increase cardiac output
by producing a positive inotropic effect, following
the activation of β1 and β2 adrenergic receptors
[13]. Dopamine has also been reported to increase
mesenterial blood flow via D1 receptor activation.
This is similar to the mechanism of renal blood
flow autoregulation [35].
Administering a selective vasodilating drug
that increases blood flow to the renal and splanchnic regions is an alternative treatment method in
ACS when surgical procedures are insufficient
[36]. Dopamine seems to be the best agent, since
it affects all adrenergic receptor types. β adrenergic effects are predominant during low-dose
dopamine infusion. On the other hand, the vasodilatory effects are camouflaged by D1 adrenergic receptor stimulation, and vasoconstriction
occurs with higher doses of dopamine (3–5 μg/kg/
/min). Although the benefits of dopamine are accepted theoretically, there is not yet a consensus
on its clinical use [36, 37]. Interestingly in another
study, it was shown that low doses of dopamine
(2 μg/kg/min) did not affect mesenteric blood flow
in sheep [38]. Hiltebrand et al. demonstrated that
dopamine significantly increases the cardiac index
(18%), and that at doses of 5–10 μ/kg/min it increased SMA flow by 33% [39]. In one of the experimental groups in the present study, ACS first
decreased splanchnic blood flow and then this was
treated by dopamine infusion. Additionally, ACS-related high vascular resistance can be controlled
by dopamine infusion.
I/R injury is an acute inflammatory response
characterized by neutrophil activation, which causes tissue damage through the production and
release of cytotoxic proteins and ROMs into the
extracellular area [40]. As the results of the present study show, in the groups with ACS the concentration of MDA, which is an indicator of lipid
peroxidation, was higher and GSH level in the
intestinal tissue was lower. This explicitly reveals
that I/R injury induces oxidative stress. Intra- and
extracellular lipid peroxidation in cell membranes
results in tissue and organ injury. On the other
hand, cells have their own defense mechanisms,
called antioxidant systems. They include A, D,
E and K vitamins, microelements and antioxidant
molecules like MPO and GSH [41]. As part of the
cellular defense system, GSH provides protection
against oxidative injury [42]. It interacts with free
radicals, creating more stable elements, so that the
lipid peroxidation is repaired [43]. In this sense,
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GSH plays an important role as an antioxidant in
limiting the propagation of free radical reactions,
which would otherwise result in extensive lipid
peroxidation.
Tissue damage induced by various causes can
result in the exhaustion of GSH [44]. In the present study, ACS significantly depleted tissue GSH
stores, indicating that GSH was used as an antioxidant for the detoxification of toxic oxygen metabolites. Dopamine exerted antioxidant effects and
perpetuated the cellular antioxidant mechanism,
so the GSH was not entirely consumed. There are
many potential sources of toxic oxygen radicals
during the reperfusion period. As stated before,
lipid peroxidation induced by free oxygen radicals
is a possible cause of tissue injury.
Moreover, the significance of circulating
polymorphonuclear leukocytes as a mediator for
ischemia reperfusion injury has been mentioned
in previous studies [45, 46]. Various enzyme ac-
tivities have been investigated in order to define
the role of neutrophils in reperfusion injury. One
of them is MPO, which increases more during reperfusion injury than in the ischemia period [47].
In the current study, as expected, ACS caused
a significant rise in MPO activity, which indicated
the contribution of neutrophil infiltration. This
increase in MPO activity was inhibited in the dopamine-treated groups.
ACS causes the accumulation of neutrophils in
tissues, and dopamine has an inhibitory effect on
the generation of free oxygen radicals. The results
of the study indicate that dopamine plays a cytoprotective role in the organs with impaired intestinal blood flow. Considering the explosive increase
in the use of laparoscopic surgery causing elevated
IAP, along with other traumatic or surgical causes
of ACS, it seems likely that low-dose dopamine
infusion might be useful in critically ill patients as
a free radical scavenger and a vasodilator.
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Address for correspondence:
Kemal T. Saracoglu
Sahrayi Cedid mah. Ataturk Cad.
Yildiz Ap. No: 1 Kat: 9 Daire: 29 Erenkoy
Istanbul 34734
Turkey
Tel.: +90 538 547 86 20
E-mail: [email protected]
Conflict of interest: None declared
Received: 23.11.2011
Revised: 17.05.2011
Accepted: 5.10.2011