Received: 15/10/2024 Accepted: 27/12/2024 Published: 27/02/2025 1 of 8
https://doi.org/10.52973/rcfcv-e35532 RevistaCientíca,FCV-LUZ/Vol.XXXV
ABSTRACT
In order to investigate the effects of acute CO poisoning and
subsequent oxygen therapy on cardiac necrosis in rats, with a
specic focus on adiponectin levels, twenty–one male Wistar
albino rats were divided into three groups (Control, CO, CO+O
2
).
The Control group was placed in a container and exposed to room
air for 30 min. Acute CO poisoning was induced in the CO group and
CO+O
2
group by exposing the rats to CO gas for 30 min. Following
CO exposure, the CO+O
2
group received oxygen therapy for 30 min,
while the CO group did not receive any additional intervention. The
animals were euthanized by cardiac puncture under anesthesia,
following the approved ethical procedures. Carboxyhemoglobin
(COHb), serum levels of creatine kinase (CK), creatine kinase
myocardial band (CK–MB), C–reactive protein (CRP) and lactate
dehydrogenase (LDH), as well as cardiac and serum adiponectin
levels were measured. CO poisoning caused necrosis in cardiac
tissue however, oxygen therapy alleviated the negative effect of CO
on cardiac injury. COHb and LDH levels in CO group were increased,
whereas both cardiac and serum adiponectin levels were decreased
(all, P<0.05). There were no changes in CK, CK–MB, CRP levels
among groups (all, P>0.05). Oxygen therapy decreased COHb, but
increased both cardiac and serum adiponectin levels (all, P<0.05).
Adiponectin and LDH may serve as potential biomarkers for early
diagnosis of cardiac necrosis caused by acute CO poisoning. The
assessment or quantication of adiponectin can also be useful
for the early prognosis of cardiac necrosis after oxygen therapy.
Key words: Adiponectin; carbon monoxide poisoning; heart;
oxygen therapy; rat
RESUMEN
Con el objetivo de investigar los efectos de la intoxicación aguda
por monóxido de carbono (CO) y la terapia de oxígeno subsiguiente
en la necrosis cardíaca en ratas, con un enfoque especíco en los
niveles de adiponectina, veintiuna ratas albinas Wistar machos
fueron divididas en tres grupos (Control, CO, CO+O
2
). El grupo de
control fue colocado en un recipiente y expuesto al aire ambiente
durante 30 min. Se indujo intoxicación aguda por CO en el grupo
CO y el grupo CO+O
2
al exponer a los ratas a gas CO durante 30
min. Después de la exposición al CO, el grupo CO+O
2
recibió terapia
de oxígeno durante 30 min, mientras que el grupo CO no recibió
ninguna intervención adicional. La eutanasia de los animales
se realizó mediante punción cardíaca bajo anestesia, siguiendo
los procedimientos éticos aprobados. Se midieron los niveles
de carboxihemoglobina (COHb), creatina quinasa (CK), banda
de creatina quinasa miocárdica (CK–MB), proteína C–reactiva
(CRP) y lactato deshidrogenasa (LDH), así como los niveles de
adiponectina cardíaca y sérica. La intoxicación por CO causó
necrosis en el tejido cardíaco; sin embargo, la terapia de oxígeno
alivió el efecto negativo del CO en la lesión cardíaca. Los niveles
de COHb y LDH en el grupo de CO aumentaron, mientras que tanto
los niveles de adiponectina cardíaca como sérica disminuyeron
(todos, P<0.05). No se observaron cambios en los niveles de CK,
CK–MB y CRP entre los grupos (todos, P>0,05). La terapia de
oxígeno disminuyó los niveles de COHb, pero aumentó tanto los
niveles de adiponectina cardíaca como sérica (todos, P<0.05). La
adiponectina y LDH pueden servir como biomarcadores potenciales
para el diagnóstico temprano de la necrosis cardíaca causada por
la intoxicación aguda por CO. La valoración o cuanticación de
adiponectina también puede ser útil para el pronóstico temprano
de la necrosis cardíaca después de la terapia de oxígeno.
Palabras clave: Adiponectina; intoxicación por monóxido de
carbono; corazón; terapia de oxígeno; rata
The effect of acute Carbon Monoxide intoxication on cardiac necrosis
in rats: in relation to Adiponectin levels
El efecto de la intoxicación aguda por Monóxido de Carbono en la necrosis
cardíaca en ratas: en relación con los niveles de Adiponectina
Gul Sahika Gökdemir
1
* , Sümeyye Çakmak
2
, Berjan Demirtas
3
, Mehmet Tahir Gökdemir
4
, Ozgur Sogut
2
,
Revşa Evin Canpolat–Erkan
5
, Fırat Aşır
6
, Beran Yokus
5
1
Mardin Artuklu University, Faculty of Medicine, Department of Physiology. Mardin, Türkiye.
2
University of Health Science, Haseki Education and Research Hospital, Emergency Department. Istanbul, Türkiye.
3
Istanbul University–Cerrahpaşa, Vocational School Veterinary Medicine, Plant and Animal Production, Equine and Training Program. Istanbul, Türkiye.
4
Mardin Artuklu University, Faculty of Medicine, Emergency Department. Mardin, Türkiye.
5
Dicle University, Faculty of Medicine, Department of Medical Biochemistry. Diyarbakır, Türkiye.
6
Dicle University, Faculty of Medicine, Department of Histology. Diyarbakır, Türkiye.
*Corresponding author: gulsahikagokdemir@artuklu.edu.tr
Carbon monoxide intoxication in Heart / Gökdemir et al.______________________________________________________________________________
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INTRODUCTION
Carbon monoxide (CO) is a gas that has no color, odor, or taste,
and it is produced as a by–product of combustion processes. This
gas originates from many industrial and domestic sources and
exposure can lead to serious health problems [1]. CO poisoning can
occur during the combustion of combustible materials, particularly
in enclosed environments, and can have serious consequences in
humans and animals [2, 3].
Acute CO poisoning leads to serious health problems especially
when the exposure occurs through inhalation [4]. Although the
pathogenesis of acute CO poisoning is not fully understood, the
primary mechanism involves hypoxic stress resulting from carbon
monoxide binding to hemoglobin, which inhibits oxygen transport
to tissues. This condition causes severe damage, particularly to
organs with high oxygen demands such as the heart and brain [5].
Although the effects of CO on human health have been
extensively studied, the effect of CO on the cardiovascular system
is poorly understood. How CO affects cardiac necrosis and how
this effect is mediated has attracted the attention of the scientic
community. Myocardial toxicity from CO exposure can result in
permanent myocardial damage and increase both short–term
and long–term mortality [6]. Normobaric and hyperbaric oxygen
therapies are very important in CO–poisoned patients, as they
prevent complications and shortens the duration of hospitalization.
Normobaric oxygen therapy may have favorable effects on the
prognosis and provide signicant economic benets [7].
Myocardial enzymes are key clinical indicators of myocardial cell
damage [8]. Creatine kinase (CK) and creatine kinase myocardial
band (CK–MB) are intracellular enzymes primarily found in the
myocardium, skeletal muscle, and brain [9].
Lactate dehydrogenase
(LDH) plays a crucial role as an enzyme in the anaerobic metabolic
pathways within the heart muscle and various other organs [10].
Consequently, LDH levels can also rise in pathological conditions
such as myocardial infarction, hematological diseases, and
circulatory failure associated with hypoxia [10].
Adiponectin is an adipokine that has recently been discovered to
play an important role in cardiac health [11].
Adiponectin is the most
abundant peptide hormone mainly secreted by adipocytes that acts
on specic receptors in various tissues including heart through
autocrine, paracrine, and endocrine signaling mechanisms [7].
Epicardial adipose tissue, located on the surface of the ventricles
and the apex of the heart, is capable of secreting adiponectin and
directly influencing heart function [12]. Adiponectin is secreted
by various other cells and tissues, such as cardiomyocytes and
endothelial cells [11].
It contributes to cardiovascular protection by
enhancing lipid metabolism, protecting vascular endothelial cells,
and preventing the formation of foam cells and the proliferation
of vascular smooth muscle cells [11]. Additionally, adiponectin
exhibits anti–inflammatory, antiapoptotic properties, mitigates
hypertrophy, enhances angiogenesis, and inhibits the development
of interstitial brosis [13]. Accordingly, adiponectin should play a
protective role against cardiovascular diseases [11]. However, there
are also some contradictory results that high adiponectin levels
have been observed in patients with cardiovascular conditions [14].
While alterations in cardiac enzyme levels are critical for
evaluating myocardial damage in acute carbon monoxide poisoning,
these indicators do not possess adequate specicity to denitively
diagnose myocardial injury, particularly in patients with skeletal
muscle necrosis or multiple organ failure [15]. Consequently, the
identication of different biomarkers for diagnosing cardiac injury
in acute CO poisoning is of great importance. It is hypothesized
that serum and cardiac adiponectin levels decrease with cardiac
injury induced by CO poisoning and that oxygen therapy increases
adiponectin levels in both serum and heart tissue.
Therefore, the aim of this study is to explore the impact of
acute CO poisoning and subsequent normobaric oxygen therapy
on cardiac necrosis in rats (Rattus norvegicus), with a focus
on adiponectin levels and other biochemical biomarkers. The
assessment of adiponectin levels may be valuable for evaluating
the cardiac necrosis and the cardiac effects of oxygen therapy,
thereby helping to optimize therapeutic strategies.
MATERIALS AND METHODS
Ethical Statement
This experimental study was approved by the University
Experimental Animals Local Ethics Committee and was conducted
following ethical rules (Ethical approval no:3 date: 26/01/2023).
Animals
Twenty–one male Wistar albino rats (8–10 weeks old; 300–350
g) were maintained in steel cages under standard conditions
(22–25°C, 12 h day/night cycle). Standard rat chow was provided
in steel containers and tap water was provided in glass bottles. All
groups were given food and water ad libitum and no feed or water
restrictions were applied to the rats during the study. All groups
of animals were part of larger experimental design previously
described in our earlier work, although different tissues were
analyzed in the current study [16].
Experimental Groups and Study Design
The rats were equally divided into three groups, with seven in
each: 1. Control, 2. CO intoxication (CO), 3. CO intoxication treated
with 100% normobaric oxygen with reservoir mask. The control
group of animals was placed in a container and allowed to breath
room air for 30 min. CO intoxication was induced according to
our previous study [16].
Briefly, the rats in CO and CO+O
2
groups
were individually placed in a 45×30×30 cm sized transparent
plastic container and exposed to CO at the concentration of 4000
ppm with the flow rate of 3 L·min
-1
CO for 30 min [17]
using a
10 L CO cylinder (Habaş Company, İzmir, Türkiye). The detector
(Dräger X–am® 5000 brand, 0–10000 ppm, Germany) was used
to determine the concentration of CO gas. Thereafter, the animals
in CO+O
2
group received 100% normobaric oxygen with the flow
rate of 15 L·min
-1
for 30 min as described in our previos study
[16].
Oxygen was administered by inhalation with a reservoir mask
(PLUSMED, Chinese) which is connected to the oxygen gas cylinder
with a flow meter.
Carbon monoxide intoxication in Heart / Gökdemir et al.______________________________________________________________________________
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Blood and tissue collection
At the end of study, all animals were eutanized by cardiac
puncture under midazolamine intraperitoneal injection anesthesia.
Thereafter, the abdomen of each animal was opened with midline
incision. Blood samples were taken from the heart’s left ventricle
using blood gas syringes (BERİKA Technology Medical, Türkiye) and
were immediately used to measure carboxyhemoglobin (COHb)
levels (ABL800 Radiometer, Denmark) [16].
Additionally, blood samples for serum adiponectin and other
biochemical biomarkers were collected into a yellow biochemistry
tube (BD Vacutainer®, USA) for the measuring of adiponectin, CK,
CK–MB, LDH and C–reactive protein (CRP).
The heart from each group of animals was excised and
longitudinally bisected into right and left halves along the septum.
The right part was kept at -80°C (Binder UF V 500 Standard Model,
Germany) until the analysis of adiponectin. Samples from the
left part were xed in 10% neutral buffered formalin for furher
histolopathological examinations.
Serum biochemical biomarkers
Blood samples collected from each animal were centrifuged
(Megafuge STPlus, Thermo Scientic, Waltham, MA) at 1500 g
for 10 min.
Serum supernatants were collected to sterile tubes, and analyzed
for levels of CK, CK–MB, LDH and CRP in a biochemical autoanalyzer
(Architect c8000; Abbott, Wiesbaden, Germany) using ultraviolet
spectrophotometric, colorimetric, and enzymatic methods. CK and
CK–MB levels of these compounds were measured using ultraviolet
spectrophotometric methods. Ultraviolet light absorption was used
to determine the concentration of these compounds. LDH levels
were determined using enzymatic methods. The enzymatic method
involves measuring the chemical reactions catalyzed by specic
enzymes to determine the concentration of the compound. CRP
levels were determined using colorimetric methods. In this method,
the color change resulting from the reaction between CRP and
chemical compounds is measured to determine the CRP levels
[18]. Serum samples were kept at -80°C for further analysis of
serum adiponectin levels.
Measurement of cardiac and serum adiponectin levels
For the analysis of cardiac adiponectin, the homogenates
were prepared from the right heart tissue stored at -80°C. Heart
tissues were removed from the freezer, placed in a glass tube with
phosphate buffer solution (PBS) at a ratio of 1:10 (w/v, pH:7.2), and
homogenized on ice with a tissue homogenizer (Bandelin, UW 2070,
Sigma, St. Louis, MO) at 30000 g for 60 s. The homogenates were
placed in centrifuge tubes and centrifuged at 4200g for 10 min at
4°C. The supernatants were transferred to an eppendorf tubes, and
the precipitates were discarded. Serum samples were also removed
from freezer. Adiponectin levels in both tissue supernatants and
serum samples were measured by enzyme–linked immunosorbent
assay (ELISA) using specic ELISA kits (Sun Red, cat. no: 201-11-
0759) according to the manufacturer’s instructions [19]. The
supernatants were read spectrophotometrically at 450 nm using
a microplate reader (Biochrom, Anthos Zenyth 200).
Histomorphological examination
The left heart tissue samples of the sacriced animals were xed
with 10% neutral formalin. After xing, all tissues were washed
under tap water, dehydrated with ascending–graded ethanol series
and embedded in parafn wax. The 5–µm sections were cut and
deparafnized in xylene solution. Thereafter, the sections were
hydrated in a descending ethanol series, stained with hematoxylin
and eosin (H&E) and visualized under a light microscope (ZEISS
Axiolab 5, Germany). The pathological findings to assess
myocardial necrosis were categorized into four grades according
to injury severity: Grade 0: normal histological appearance, Grade
1: scattered necrotic cells, Grade 2: one or two necrotic foci, and
Grade 3: more than two necrotic foci [20].
Statistical analysis
SPSS 26 software (SPSS Inc., Chicago, IL, USA) was used for the
statistical analysis and graphics. A Shapiro–Wilks test was used
to conrm the normality of the distribution in each group. Since
the distributions were normal, statistics for continuous variables,
including the mean and standard deviation (SD), were calculated.
ANOVA test was employed to detect differences in the continuous data
and Tukey’s test used for comparisons between groups. Pearson’s
correlation analysis was applied to detect the positive and negative
relationships between the data. While P<0.05 values are considered
statistically signicant, P<0.001 indicates a stronger association,
emphasizing the robustness of the results in certain comparisons
[21]. The use of these two signicance levels was determined by the
magnitude of the observed differences and the need to emphasize
different degrees of statistical condence. This two–level approach
was used for a more detailed interpretation of the data.
RESULTS AND DISCUSION
Levels of blood COHb and serum biochemical biomarkers
Blood COHb levels and serum levels of CK, CK–MB, LDH and
CRP are shown in TABLE I.
For the current study, the experimental conditions were identical
to those in our previous study, which focused on liver damage,
where the same cohort of animals was used and the same protocols
TABLE I
The levels of blood carboxy haemoglobin and serum
biochemical biomarkers in all study groups
Parameters Control (n=7) CO (n=7) CO+O
2
(n=7)
COHb (%) 0.71 ± 0.34
a
90.27 ± 1.36
b
34.03 ± 7.57
c
CK–MB(pg·mL
-1
) 218.43 ± 184.62
a
225.85 ± 120.58
a
241.01 ± 186.98
a
LDH(u·L
-1
) 304.57 ± 134.08
a
1129.43 ± 345.68
b
901.71 ± 508.94
b,d
CK(u·L
-1
) 589.86 ± 125.14
a
651.43 ± 359.04
a
621.43 ± 189.36
a
CRP(mg·L
-1
) 0.11 ± 0.02
a
0.11 ± 0.02
a
0.12 ± 0.01
a
Dataarerepresentedasmean ± standarddeviation.Dierentsuperscriptsinthesame
rowindicatestatisticallysignicantdierences.
a–b,a–c,b–c
indicatesignicantdierencesat
P<0.001.
a–d
indicatessignicantdierencesatP<0.05. CO: Carbon monoxide intoxication
group;CO+O
2
:Carbonmonoxideintoxicationtreatedwith100%normobaricoxygen
group;COHb:Carboxyhemoglobin;CK–MB:Creatinekinasemyocardialband;LDH:
LactatedehydrogenaseCK:Creatinekinase;CRP:C–reactiveprotein
Carbon monoxide intoxication in Heart / Gökdemir et al.______________________________________________________________________________
4 of 8 5 of 8
were followed [16]. Given that COHb is the only indicator of CO
poisoning [22], we employed the COHb data from the same
cohort of animals used in our previous study [16]. COHb level
was signicantly higher in CO group than in that of the control
group (P<0.001). COHb level was signicantly decreased in CO+O
2
group compared to CO group (P<0.001). However, COHb level was
still signicantly higher in CO+O
2
than control group (P<0.001).
There were no signicant differences in CK, CK–MB and CRP
levels among the groups (all, P>0.05). LDH level was signicantly
increased in CO group compared to control group (P<0.001). There
were no signicant differences in LDH levels between CO and
CO+O
2
(P>0.05). LDH level was still signicantly higher in CO+O
2
group than control group (P<0.05). LDH levels were positively
correlated with COHb (R=0.649; P=0.001).
CO poisoning mainly results from the formation of COHb, which
prevents oxygen delivery to tissues, and causes hypoxia [23]. In
patients with CO intoxication, COHb levels at the moment of the
intoxication are signicant predictors of the late appearance of
myocardial infarction [24]. Neurological and structural damage may
occur in cardiac tissue as hypoxia intensies [6, 25]. CO poisoning
induces a wide range of cardiac pathologies through mechanisms
involving tissue hypoxia and direct cellular injury [26]. In this study,
CO group had signicantly higher COHb level compared to the
control. Oxygen (O
2
) treatment signicantly reduced the COHb
level in CO+O
2
group, however, it was still signicantly higher than
control group. This might be due to shorter duration of oxygen
therapy, which was only 30 min [16]. In addition to the shorter
duration of oxygen therapy, another known factor contributing to
this phenomenon is the more stable binding between hemoglobin
and carbon monoxide. This stable binding prolongs the presence
of CO in the bloodstream, even with short–term exposure, and
may impact the recovery process [3, 27].
Myocardial necrosis occurs during moderate and severe CO
poisoning, with changes in the electrocardiography and biomarkers
[25]. Although CO exposure leads to alterations in cardiac
biomarkers, the prognostic value of these indirect indicators of
myocardial following CO intoxication remains unclear. Myocardial
enzymes such as CK, CK–MB, CRP and LDH are used as the primary
clinical indicators for assessing myocardial cell injury [8, 28]. In
this study, no signicant changes were found in serum CK, CK–
MB, and CRP levels among the control, CO, and CO+O
2
groups.
Similarly, no signicant changes in CK and CK–MB have been
reported in children at early time points of CO poisoning [29]. It
has been reported that serum CK and CK–MB levels usually occur
4-6 hours (h) after the onset of myocardial damage, peak at 24 h,
and return to baseline within 48-72 h [30]. Similar to these results,
it has also been shown that CRP levels do not increase in patients
with severe CO poisoning [31]. However, it has been shown that
both CK–MB, and CRP levels have been increased in acute CO
poisoning patients [5, 28]. In an other sudy, patients with acute
poisoning, CRP levels have been observed to be at their lowest
on the rst day and peaking on the third day before decreasing
thereafter [32]. The biomarkers were measured 30min after CO
exposure to capture the early effects of acute CO poisoning. This
time point was chosen based on the understanding that the half–
life of CO in ambient air is 4-5 h, but with 100% oxygen therapy,
it is reduced to 1 h, allowing for the observation of early effects
within this timeframe [33]. Since we measured these biomarkers
at 30 min after CO exposure, acute CO poisoning migth have not
caused any signicant changes in CK, CK–MB and CRP levels
compared to the control group. However, in this study, the LDH
level was signicantly increased in the CO group compared to
the control group. The increase in LDH levels in the CO group
compared to the control group is an expected result, given the toxic
mechanism of action of carbon monoxide. Carbon monoxide binds
to hemoglobin, reducing oxygen delivery to tissues and resulting
in cellular hypoxia. This hypoxic condition promotes the release
of enzymes like LDH, which are typically elevated in response
to cell damage [27]. Moreover, carbon monoxide poisoning may
result in rhabdomyolysis, a potentially life–threatening condition
that is characterized by the breakdown of skeletal muscle and
the release of muscle cell contents, including enzymes like LDH,
into the bloodstream. This process further supports the elevation
of LDH levels in the CO group, as rhabdomyolysis can be a direct
consequence of CO toxicity [4]. Similar to our results, LDH levels
have been reported to increase in rabbits exposed to acute CO
poisoning [34]. In clinical studies, LDH levels have also been found
to be elevated in patients with severe, acute CO poisoning [35].
The rise in LDH levels may occur earlier than CK, CK–MB, and CRP
levels, which are more specic to muscle damage or inflammation
and may take longer to become elevated. In this study, oxygen
therapy did not cause any signicant change in LDH levels in CO–
poisoned rats. This might be due to the shorter duration of oxygen
therapy, which was only 30 min.
Cardiac and serum adiponectin levels
TABLE II shows the adiponectin levels in the cardiac tissues
and serum of all groups. The cardiac adiponectin level in CO group
was signicantly lower than that in the control group (P<0.001).
However, cardiac adiponectin level in CO+O
2
group was signicantly
increased compared to CO group (P<0.05). Moreover, there were no
signicant differences between control and CO+O
2
levels (P>0.05).
Serum adiponectin level in CO group was signicantly lower than
that in the control group (P<0.001). However, serum adiponectin
level in CO+O
2
group was incresed significantly compared to
CO group (P<0.05). There was a signicant difference between
control and CO+O
2
groups (P<0.05). Moreover, there was a
positive correlation between cardiac and serum adiponectin levels
(R=0.686; P=0.001) (FIG. 1). This positive correlation may suggest
a systemic regulation of adiponectin levels during acute stress
conditions, as both cardiac and serum adiponectin levels are known
to respond to inflammatory and oxidative stress pathways [36].
TABLE II
Cardiac and serum adiponectin levels in all study groups
Control (n=7) CO (n=7) CO+O
2
(n=7)
CardiacAdiponectin(ng·mL
-1
)
7.99 ± 1.53
a
3.47 ± 1.82
b
6.16 ± 1.61
a,c
SerumAdiponectin(ng·mL
-1
)
5.64 ± 1.05
a
3.36 ± 0.32
b
4.42 ± 0.47
d
Dataarerepresentedasmean ± standarddeviation.Dierentsuperscriptsinthesame
rowindicatesignicantdierences.
a–b
indicatessignicantdierencesatP<0.001.
b–c,a–d,
b–d
indicatesignicantdierencesatP<0.05.CO:Carbonmonoxideintoxicationgroup;
CO+O
2
:Carbonmonoxideintoxicationtreatedwith100%normobaricoxygengroup
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Cardiac adiponectin levels were inversely correlated with
COHb and LDH (R= -0.780; P=0.001 and R= -0.662; P=0.001,
respectively) (TABLE III). Similarly, serum adiponectin levels
were inversely correlated with both COHb and LDH (R= -0.823;
P=0.001 and R= −610; P=0.003, respectively) (TABLE III). This
inverse correlation may be explained by the anti–inflammatory and
cytoprotective roles of adiponectin, which are likely downregulated
in the presence of increased oxidative stress and cellular damage,
as indicated by elevated COHb and LDH levels. Further studies are
needed to explore this hypothesis in detail [36].
Adiponectin is an adipokine secreted by adipocytes,
cardiomyocytes and endothelial cells as well as pericardial
and perivascular tissues, and directly affect the function of the
cardiovascular system [11].
However, the relationship between
adiponectin levels and the incidence of cardiovascular diseases
is controversial [37]. Some clinical studies support the idea that
populations with higher adiponectin levels are less likely to suffer
from cardiovascular disease [13]. In contrast, higher adiponectin
levels have been associated with an increased risk of cardiovascular
diseases such as heart failure and myocardial infarction [37, 38].
To the best of current knowledge, no studies have been
conducted on adiponectin levels in animals or humans exposed
to CO intoxication. Moreover, no research has been found regarding
the correlation between cardiac and serum adiponectin levels in
CO–induced cardiac injury. This study showed that there was a
positive correlation between cardiac and serum adiponectin levels.
In our study, both cardiac and serum adiponectin levels were
decreased signicantly in CO group, but both were increased
following oxygen treatment. Moreover, both adiponectin levels
were inversely correlated with LDH and COHb levels. These ndings
suggest that the adverse effects of CO on cardiac health may be
related to a decrease in adiponectin levels, and oxygen therapy
may ameliorate the negative effects of acute CO poisoning on
cardiac tissue by elevating adiponectin levels.
Macroscopic and Histomorphological Observations
The macroscopic appearance of heart tissues in all groups of
animals has been shown in FIG. 2. In all groups of animals, the
anatomical structure, general size and shape of the heart and the
thickness of ventricular wall were in normal limits. Additionally,
there was no discoloration in the control group. Diffuse congestion
was detected in all animals of CO group compared to control.
The degree of congestion was less in all animals of CO+O
2
group
compared to CO group.
The histological observations and the degenerative grading scores
in all groups are shown in FIG. 3 and TABLE IV, respectively. The
heart tissue of the control group had normal histological structure.
CO poisoning group had more than two necrotic foci in heart tissue,
whereas CO+O
2
group had only scattered necrotic cells. The
degenerative grading score in CO group was higher than that in control
group (P<0.001). The degenerative score in the CO+O
2
group was
signicantly lower than that in the CO group (P<0.05), but it remained
signicantly higher than that of the control group (P<0.001) [21].
In this study, discoloration and diffuse congestion in the heart
were detected in all animals in the CO group, however, O
2
therapy
reduced the extent of congestion. Similarly, in both humans and
animals, CO poisoning has been reported to be characterized by
red discoloration of the skin, mucous membranes, cardiomyocytes,
as well as neurological alterations, including necrosis in the brain
[3, 39, 40]. Cardiac necrosis refers to damage and death of heart
tissue and has serious consequences on cardiovascular health. In
this study, necrotic foci were observed in the heart tissue of the
CO group, however, early O
2
treatment alleviated this necrosis.
Similarly, necrosis in cardiac tissue has been observed in a rat
model following CO poisoning [41]. Furthermore, it has been
reported that normobaric oxygen therapy can reduce the cardiac
necrosis in patients with CO poisoning [42].
0 2 4 6 8 10 12
0
1
2
3
4
5
6
7
8
Serum Adiponectin
Cardiac Adiponectin
R=0.686; P=0.001
FIGURE 1. Correlation between cardiac and serum adiponectin levels. R: Pearson
correlation coecient. Signicant correlation, level of signicance P<0.001
TABLE III
Correlation analysis of all parameters
Variables Cardiac ADN (R ; P) COHb (R ; P) LDH (R ; P) CK (R ; P) CK–MB (R ; P) CRP (R ; P)
CardiacADN – -0.780;0.001* -0.662;0.001* -0.221;0.336 0.088;0.703 0.111;0.631
SerumADN 0.686;0.001* -0.823;0.001* -0.610;0.003* -0.191;0.406 0.071;0.758 0.117;0.615
R:Pearsoncorrelationcoecient.*:Signicantcorrelation,levelofsignicance
P<0.05.CardiacADN:Cardiacadiponectin;SerumADN:
Serumadiponectin;COHb:Carboxyhemoglobin;LDH:lactatedehydrogenase;CK:creatinekinase;CK–MB:creatinekinasemyocardial
band;CRP:C–reactiveprotein
Carbon monoxide intoxication in Heart / Gökdemir et al.______________________________________________________________________________
6 of 8 7 of 8
biomarkers for early diagnosis of cardiac necrosis caused by acute
CO poisoning. Adiponectin may also be of value in early prognosis
of cardiac necrosis. However, more comprehensive studies are
needed to establish the precise cut–off values of adiponectin and
LDH to improve their diagnostic accuracy and clinical reliability as
biomarkers for cardiac necrosis caused by CO poisoning.
Furthermore, adiponectin might be used as an adjunctive
therapeutic agent in addition to oxygen therapy for CO–induced
cardiac injury. The relationship between adiponectin and the
molecular pathways involved in CO–induced cardiac necrosis—
such as oxidative stress, inflammation, and apoptosis—requires
further investigation.
Conflict of Interest
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
CONCLUSION
Exposure to CO induces cardiac necrosis and reduces the levels
of both cardiac and serum adiponectin. Oxygen therapy may
alleviate the negative effects of acute CO poisoning on cardiac
injury by increasing both cardiac and serum adiponectin levels. It
can be concluded that adiponectin and LDH may serve as potential
1 2 3 4 5 6 7
1 2 3 4 5 6 7
1 2
Control
CO Intoxication
CO + O
2
3 4 5 6 7
FIGURE 2. Macroscopic appearance of hearts in all rats according to groups. CO: carbon monoxide intoxication group; CO+O
2
: carbon monoxide intoxication treated
with 100% normobaric oxygen group
a b c
FIGURE 3. Histomorphological appearance of each study group. A: Control group: B: Carbon monoxide intoxication group C: Carbon monoxide intoxication treated with
100% normobaric oxygen group. *: Necrotic foci. Staining: hematoxylin and eosin; scale bar: 50 μm; magnication: 20 μm
TABLE IV
The degree of cardiac degeneration in all study groups
Groups Heart Degeneration Grading
Control(n=7) 0.29 ± 0.49
a
CO(n=7) 2.71 ± 0.49
c
CO+O
2
(n=7) 1.86 ± 0.69
b
Dataarerepresentedasmean ± standarddeviation.Dierentsuperscriptsinthesame
columnindicatesignicantdierences.
a–b,a–c
indicatesignicantdierencesatP<0.001.
b–c
indicatessignicantdierencesatP<0.05.CO:Carbonmonoxideintoxicationgroup;
CO+O
2
:Carbonmonoxideintoxicationtreatedwith100%normobaricoxygengroup
Carbon monoxide intoxication in Heart / Gökdemir et al.______________________________________________________________________________
_________________________________________________________________________________________________Revista Cientica, FCV-LUZ / Vol.XXXV
7 of 8
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