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Abstract
Background and the purpose of the study: Blood contact with artificial surfaces of the extracorporeal circuit and
ischemia-reperfusion injury in CABG with CPB, may lead to a systemic inflammatory response. Hypertonic saline
have been recently investigated as a fluid in order to decrease inflammatory response and cytokines generation in
patients undergo cardiac operations. Our purpose is to study the prophylactic effect of HS 5% infusion versus NS
on serum IL-6 as an inflammatory & IL-10 as an anti-inflammatory biomarker in CABG patients.
Methods: The present study is a randomized double-blinded clinical trial. 40 patients undergoing CABG were
randomized to receive HS 5% or NS before operation. Blood samples were obtained after receiving HS or NS, just
before operation, 24 and 48 hours post-operatively. Plasma levels of IL-6 and IL-10 were measured by ELISA.
Results and major conclusion: Patients received HS had lower levels of IL-6 and higher level of IL-10 compared
with NS group, however these differences were not statistically significant. Results of this study suggest that
pre-treatment with small volume hypertonic saline 5% may have beneficial effects on inflammatory response
following CABG operation.
Keywords: CABG, CPB, Hypertonic saline 5%, Inflammation, IL-6, IL-10
© 2012 Mazandarani et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Mazandarani et al. DARU Journal of Pharmaceutical Sciences 2012, 20:49 Page 2 of 7
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with traumatic hemorrhagic shock [1]. HS solution also molecules leading to interaction between endothelial
reduced pro-inflammatory tumor necrosis factor (TNF)- cells therefore play a critical role in extending the tissue
alpha production significantly, while increasing anti- damage [30].
inflammatory IL-10, thus altering the balance between IL-10 is a prototypical endogenous anti-inflammatory
pro-inflammatory and anti-inflammatory cytokines [4,5]. and immunosuppressive cytokine [31], which inhibits
Coelho and collageous [21], demonstrated that expres- monocyte/macrophage activation and down-regulates
sion of cyclooxygenase (COX)-2 and inducible nitric the biosynthesis of TNF-α and IL-1β, while preventing
oxide synthase (iNOS) was markedly increased in the their biologic actions via up-regulation of IL-1ra [32].
pancreas of the acute pancreatitis patients and was IL-10 also decreases leukocyte adhesion and its recruit-
reduced by treatment with HS. HS also reduced the ment to sites of inflammation [31]. Together these med-
levels of TNF-alpha and IL-6 but not of IL-10 in the iators serve to limit the potentially injurious effects of
pancreatic tissue. In another study, Coimbra and col- excessive inflammatory reactions [32]. Several recent
lageous [22] demonstrated that HS reduce traumatic investigations have shown that early therapeutic admin-
shock induced T-cell dysfunction. istration of IL-10 is effective in preventing the initial
IL-6 is produced by monocytes, lymphocytes, and surge in TNF-α observed after traumatic hemorrhagic
endothelial cells. IL-6 induces the adhesive neutrophil- shock [33], and also in reducing the systemic inflamma-
cardiac myocyte interaction and myocardial damage tory response and lethality in murine models of sepsis
following CPB surgery. Highest plasma level of IL-6 sig- and reperfusion injury [34].
nificantly correlated with the duration of SIRS [23] and Higher levels of IL-10 in HS group of our study may
also outcome in other setting of SIRS positive patients indicate its ability to evoke host anti-inflammatory cyto-
like [24-27]. Results of this study indicated anti- kines to reduce reperfusion damage.
inflammatory effect of pre-operative administration of HS solutions have benefits on cardiac outputs, because
HS in patients undergoing CABG (Figure 1). IL-6 of the increasing preload (venous return and volume
plasma levels were lower (but not statistically significant) expanding effect) and decreasing afterload (vasodilation
in HS group during 48 h after surgery. This effect may and reduction in pulmonary and systemic vascular re-
be justified by HS osmotic effect. Osmotic effects of HS sistance) [1,35]. Whether cardiac output improving, be-
solution resulted in fluid shift from intracellular to the cause of the direct effect of HS on increasing cardiac
interstitial and intravascular space [1]. contractility and having inotropic effect or due to pre-
In the state of ischemia (duration of aortic cross load effect must be further investigated [1,35]. In our
clamp) endothelial surface layer thickness and glycocalyx study we have found that patients receiving HS required
structure have impaired, and dimension of glycocalyx inotropic support more frequently comparing to normal
degradation was proportional to the duration of ische- saline group (4 vs. 2 p = 0.366) in the first 24 h after sur-
mia [28], therefore endothelial cell membrane ion ex- gery, that may refute cardiac benefits of HS, but not sta-
change has disturbed and ATP loss has occurred [1]. tistically significant. We can explain this phenomenon,
Destruction of the glycocalyx could be a trigger for that myocardial stunning or altering in beta-receptor
increased trans-endothelial permeability leading to the function as a result of ischemia-reperfusion injury oc-
development of tissue edema. Pre-operative use of HS curred in some of them. Moreover patients receiving HS
induces normalization of endothelial cell volume and had lower systolic and diastolic pressure in comparison
edema that increase capillary diameter and reduce resist- with NS receiving group which can due to possible tran-
ance to flow. Therefore plasma viscosity is reduced as a sient hypotensive effect after administration of hyper-
result of the plasma volume expansion [1]. Hypertonicity tonic saline, which was noted by Boldt J and collageous's
has a direct relaxant effect on vascular smooth muscle [36]. We can suggest designing another study using HS
with resultant arteriolar vasodilatation [1]. Overally, during CPB, because in this period dropping of blood
these physiological effects result in increased capillary pressure is more considerable. Looking at the positive
blood flow and this improvement observed in all areas clinical trend of our patient’s treatment groups chal-
of microcirculation by HS [1]. lenged with HS, higher dose of HS could be considered
After declamping aorta and reestablishing the micro- in a larger sample size study following CABG to reach
vascular perfusion, the ischemic process has been improved statistical and clinical results.
stopped by supplying the oxygen and nutrients, but at Limited number of eligible candidate for intervention
the same time a cascade of events has similar character- with hypertonic saline before CABG, uni-center nature
istics to inflammatory response is rapidly initiated. This of the study, high cost of cytokine evaluation and ethical
inflammatory-like response to ischemia-reperfusion, concern regarding the safety of hyperoncotic fluids on
mediated largely by neutrophils [29]. Stimulated poly- subject with venerable hemodynamic profiles were mean
morphonuclears (PMNs) via the expression of adhesion parts of our study’s limitations.
Mazandarani et al. DARU Journal of Pharmaceutical Sciences 2012, 20:49 Page 6 of 7
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doi:10.1186/2008-2231-20-49
Cite this article as: Mazandarani et al.: Comparison of hypertonic saline
versus normal saline on cytokine profile during CABG. DARU Journal of
Pharmaceutical Sciences 2012 20:49.