Effects Of ω-3Fish Oil Fatty Emulsion On In Inflammatory Response In Patients With Cardiac Disease

Background Cardiopulmonary bypass(CPB) is one of the most important measures during heart surgery. However, cardiopulmonary bypass, which is not an physiological circulation mode, may activated systemic inflammatory response syndrome(SIRS),which can bring the risk of dysfunction of heart, lung, liver, kidney, brain and so on. In that situation, there will be a significant increase in mortality and morbidity in patients. Surgical wounds, the blood contact with the surface of foreign directly, organ ischemia and reperfusion,release of intestinal endotoxin from bacterial translocation and temperature changes lead to activation of neutrophils, monocytes, leukocytes,endothelial cells and platelet, as well as complement, endogenous coagulation system, extrinsic coagulation system and fibrinolytic system,which may activated systemic inflammatory response syndrome. In recent years, a large number of research data shows Tumor necrosis factor(TNF-a)、Interleukin-1(IL-1)、 Interleukin-6(IL-6)、Interleukin-8(IL-8) and Interleukin-10(IL-10) play an important role in systemic inflammatory response syndrome(SIRS) caused by cardiopulmonary bypass during heart surgery. Interleukin-1(IL-1)、Interleukin-6(IL-6) and Interleukin-8(IL-8) are known as pro-inflammatory mediators.On the contrary, Interleukin-10(IL-10) are known as the anti-inflammatory mediator. Research found that the concentration of plasma interleukin-6increased at the moment of cardiopulmonary bypass, reached its first peak two hours later, decreased to the level of before incision five to six hours later, reached its second peak two twelve to eighteen hours later, and decreased again to the level of before incision forty eight hours later. the concentration of plasma interleukin-10increased at the moment of aortic opening time, reached its first peak ninety minutes later, decreased to the level of before incision four hours after cardiopulmonary bypass. The right amount of anti-inflammatory mediators are benefit for the control of inflammation progress and stability of the environment, but also excessive anti-inflammatory response of the body can produce immunosuppression, which is known as compensatory anti-inflammatory response syndrome(CARS). The emergence and development of SIRS is an extremely complex cascade process, the severity of SIRS is dominated by the pro-inflammatory cytokines (mainly IL-6, IL-8) and anti-inflammatory cytokines (mainly IL-10) in the equilibrium state in the development process due to cardiopulmonary bypass. With the development in medical technology, there are a variety of effective method to reduce the inflammatory response during cardiopulmonary bypass, such as the application of biocompatible coating materials, pulsatile perfusion mode,leukocyte filters, ultra-filtration, corticosteroids, ulinastatin, phosphodiesterase inhibitors, monoclonal antibodies, etc.Omega-3polyunsaturated fatty acids are polyunsaturated fatty acids, including a-Linolenic acid(ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In nature, Omega-3polyunsaturated fatty acids mainly from aquatic phytoplankton and deep-sea fish. Whereas, terrestrial plants and animals almost have no Omega-3polyunsaturated fatty acids. Studies have shown that Omega-33polyunsaturated fatty acids can regulate the body’s inflammatory and immune responses in the following ways:(1) through the influence of arachidonic acid (Arachidonic Acid, AA) metabolism.(2) changes in membrane fluidity.(3) effects on the role of certain inflammatory and immune mediators.(4) changes in signal transduction and gene expression in the regulation of immune cells.In recent years, Omega-3fatty acids in cardiac protection attracted more and more attention. Mc Guinness found that Omega-3fatty acids preconditioning can also reduced myocardial infarct size by induced a great expression of heat shock protein (HSP). Charman found that before cardiopulmonary bypass surgery, giving patients fish oil (the main component of Omega-3polyunsaturated fatty acids), can reduce myocardial injury caused by cardiopulmonary bypass surgery. Studies have also reported that Omega-3fatty acids can reduce the myocardial oxygen consumption, oxidative stress and the loss of K+during myocardial ischemia reperfusion, and thereby reduce reperfusion arrhythmias.A large-scale clinical trial found that500mg to1000mg daily intake of polyunsaturated fatty acids can significantly reduce the risk of cardiovascular events. Currently in clinical practice, focusing on adding Omega-3polyunsaturated fatty acids, the first type of fat emulsion:Omega-3fish oil fat emulsion came out and used clinically in sepsis, systemic inflammatory response syndrome, severe trauma, after major surgery of head and abdomen,achieving better results in the treatment of critically ill patients. However, the supplement Omega-3fish oil fat emulsion, used as an anti-inflammatory treatment during cardiopulmonary bypass surgery, is still rare reported at home and abroad.Objective To evaluate the impact of ω-3fish oil fatty emulsion on interleukin-6(IL-6) and interleukin-10(IL-10) in patients with operation of cardiopulmonary bypass cardiac surgical procedures.Method A total of30patients with cardiac disease receiving cardiopulmonary bypass were randomly assigned to two groups:trial group (n=15) and control group (n=15). The patients in trial group were administered ω-3fish oil fatty emulsion0.2g/kg.Patients in control group received saline. Clinical data pre-operation(age,sex,height,weight,history of disease), hospital-related summary of results during operation time (surgeon time, cardiopulmonary bypass time, aortic clamping time, bleeding volume), hospital-related summary of results post-operation (bleeding volume, the period of ventilation, the period of antibiotics, the period of Intensive Care Unit, transfusion volume) were observed. At the time point of before incision (T1),30minutes after aortic clamping time (T2),1hour after aortic clamping time (T3),30minutes1hour after aortic opening time (T4),1hour after aortic opening time (T5),6hours at the end of cardiopulmonary bypass (T6),12hours (T7),24hours (T8),48hours (T98),72hours (T10) post-operation, plasma concentration of IL-6and IL-10were examined in both groups.Results1.There were no difference between the two groups in age (trial group49.8+8.7,control group49.4+11.9), sex (man,trial group46.7%,control group40%),height (trial group162.5+11.4cm,control group159.6±9.7cm),weight (trial group66.6+13.5kg,control group61.1±11.6kg)and history of disease, P>0.05.2. surgeon time (trial group249.2±44.8min, control group241.1±37.4min), cardiopulmonary bypass time(trial group95.5±53.7min, control group95.3+31.4min), aortic clamping time(trial group69.8±44.0min, control group68.2±28.1min) and bleeding volume(trial group800+185.9ml, control group741.4±288.3ml) were not statisticaly significant(P>0.05).3. There were also no difference between the two groups in bleeding volume(trial group598.8±162.5ml, control group687.3±276.7ml), the period of ventilation (trial group12.8±5.3h, control group12.1±5.1h), the period of antibiotics(trial group3.4+1.2d, control group3.5±1.5d), the period of Intensive Care Unit(trial group2.8±0.8d, control group3.2+0.9d) and transfusion volume(trial group741.6+698.6ml, control group492.9+503.0ml).4. The plasma concentration of IL-6examined in both groups were:T1(trial group6.81±0.20pg/ml, control group6.71±0.16pg/ml),T2(trial group 10.66±1.61pg/ml, control group15.80+1.54pg/ml)T3(trial group29.16±4.73pg/ml, control group53.43+5.15pg/ml),T4(trial group101.02±7.61pg/ml, control group130.62±9.83pg/ml),T5(trial group182.38±11.73pg/ml, control group207.9±16.21pg/ml),T6(trial group86.91±14.49pg/ml, control group132.91±15.21pg/ml),T7(trial group43.08±10.26pg/ml, control group98.58+10.17pg/ml),T8(trial group8.21±1.66pg/ml, control group29.57±9.42pg/ml),T9(trial group6.71±0.16pg/ml, control group11.14±3.2pg/ml),T10(trial group6.50±0.17pg/ml, control group6.71±0.16pg/ml). The plasma concentration of IL-6examined at T2-T9were significantly higher than T1in both groups,P<0.01. The plasma concentration of IL-6in control group were significantly higher than that in trial groups,P<0.01.5. The plasma concentration of IL-10examined in both groups were:Tl(trial group21.88±4.14pg/ml, control group13.14±0.60pg/ml),T2(trial group59.58±11.93pg/ml, control group49.93±6.44pg/ml)T3(trial group262.34±20.99pg/ml, control group150.05±17.70pg/ml),T4(trial group390.27±1.09pg/ml, control group303.53±34.72pg/ml),T5(trial group299.32±41.63pg/ml, control group206.58±30.22pg/ml),T6(trial group115.66±21.06pg/ml, control group89.42±12.95pg/ml),T7(trial group63.64±13.29pg/ml, control group44.45±14.65pg/ml),T8(trial group52.11+9.67pg/ml, control group23.36+7.37pg/ml),T9(trial group30.03±7.05pg/ml, control group18.89±6.14pg/ml),T10(trial group19.29+5.36pg/ml, control group12.73+0.44pg/ml).The plasma concentration of IL-10examined at T2-T9were significantly higher than T1in both groups,P<0.05. The plasma concentration of IL-10examined at T10were significantly higher than T1in both groups,P<0.01. The plasma concentration of IL-10in trial group were significantly higher than that in control groups,P<0.01.Conclusion ω-3polyunsaturated fatty acids can improve immune status, enhance immunity, and reduce inflammation in patients with operation of cardiopulmonary bypass cardiac surgical procedures.