| Part OneRelationship between myocardial inflammatory response and the myocardial protective effect of on-pump beating-heart techniqueObjective:To study the effect of myocardial inflammatory response on the myocardial protective of on-pump beating-heart technique in patients involving open heart valve surgery.Methods:The randomised controlled trial was performed at Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangxi Medical University, from September2010to February2011. Forty patients undergoing elective artificial mechanical heart valve replacements with CPB were randomly divided into conventional group and beating heart group,20cases in each group. While the conventional approach was used for20patients in the conventional group, the heart was kept empty and beating throughout the operation in the beating heart group.In all patients, blood samples withdrawn at (T1)before CPB,(T2)30min after CPB commencement,(T3) when the right atrium was closed,(T4)24h,(T5)72h, and (T6)120h after weaning from CPB were assayed for cardiac troponin Ⅰ (cTnI) and CK-MB. Meanwhile,right atrial myocardial tissue samples were taken to detect myocardial interleukin (IL)-6, IL-8, IL-10,tumor necrosis factor-alpha (TNF-a), and NF-KBp65concentrations when the right atrium was opened and closed.Results:In both groups, compared with the baseline values, plasma levels of cTnI and CK-MB were increased during CPB. Compared to the conventional group, the increasing degrees of cTnI and CK-MB were significantly lower in the beating heart group (P<0.05). The plasma levels of cTnI and CK-MB returned to normal early in the beating heart group. TNF-a, IL-6, IL-8, IL-10concentrations when the right atrium was closed were larger than those when the right atrium was opened in the two groups. But the elevated levels were lower in beating heart group than conventional group. IL-6/IL-10ratio was increased in conventional group, while the change was not statistically significant in bearting heart group.The correlation coefficients between cTnI concentration and TNF-a, IL-6, IL-8, IL-10NF-KBp65contents were0.749,0.696,0.788,-0.475,0.695(P<0.05). The correlation coefficients between CK-MB concentration and TNF-a, IL-6,IL-8, NF-KBp65,and IL-10contents were0.680,0.614,0.669,0.059,0.518.Conclusion The results of the study illustrate that decreased myocardial inflammatory reaction is associated with myocardial protection by the beating heart valve replacement with mild hypothermia. Part TwoReduced endoplasmic reticulum stress play an important role in the myocardial protective effect of on-pump beating-heart technique with mild hypothermia in patients with artificial mechanical heart valve replacements.Objective:To investigate the interaction between local inflammatory reaction pathway and myocardial endoplasmic reticulum stress (ERS) during the open heart surgery involving CPB,and to study whether the reduced ERS play an important role in the myocardial protective effect of on-pump beating-heart technique with mild hypothermia in patients with artificial mechanical heart valve replacements.Methods:The randomised controlled trial was performed at Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangxi Medical University, from September2010to February2011. Forty patients undergoing elective artificial mechanical heart valve replacements with CPB were eligible for inclusion in the study. The patients were randomly divided into conventional group and beating heart group,20cases in each group. While the conventional approach was used for20patients in the conventional group, the heart was kept empty and beating throughout the operation in beating heart group.Right atrial myocardial tissue samples were taken to detect myocardial Caspase-4mRNA, NF-KBp65mRNA,and GRP78mRNA expressions using real-time fluorescence quantitative PCR and Caspase-4, NF-κBp65,and GRP78protein expressions using Western blot when the right atrium was opened and closed.Results:There were no significant differences between the two groups in terms of demographic and pre-operative parameters.In both groups, compared with the baseline values, mRNA and protein levels of Caspase-4,NF-KBp65,and GRP78were increased when the right atrium was closed. Compared to the conventional group, the increasing degrees of Caspase-4, NF-KBp65, and GRP78were significantly lower in the beating heart group (P<0.05).Conclusion:There are myocardial local inflammatory response pathway activation and ERS in the process of open-heart operation involving CPB.The attenuated ERS, through the reduced interaction of PERK-eIF2alpha, IRE1alpha-TRAF2pathway and NF kappaB pathway, may plays a important role in myocardial protection by on-pump beating-heart technique with mild hypothermia. Part ThreeMetabonomics study of serum in patients involving heart valve replacement under cardiopulmonary bypassObjective:To investigate the system detects about the impact on the patients undergoing beating heart valve replacement under mild hypothermia involving CPB in order to enrich the theoretical foundation of the new surgical approach,using metabolomics, a new research platform, and high performance liquid chromatography-ultraviolet detection (HPLC-UV).Methods:Thirty male patients undergoing elective artificial mechanical heart valve replacements with CPB were eligible for inclusion in the study. These patients were randomly divided into conventional group and beating heart group,15cases in each group. While the conventional approach was used for15patients in the conventional group, the heart was kept empty and beating throughout the operation in beating heart group. In all patients, blood samples withdrawn from venous at:(T1) after successful arterial puncture before surgery, (T2) after the induction of anesthesia,(T3) cooling the body temperature to32-33℃during CPB,(T4) end of CPB,(T5)3h,(T6)24h,(T7)48h, and (T8)72h after weaning from CPB, were assayed for postoperative metabolite using NMR-based metabolomics. Meanwhile, adenine nucleotide changes in the serum were detected using HPLC-UV.Results:There were significantly different about serum metabolic spectrum in different groups at the same time point and in the the same group at different time points.The concentration changes of valine, tyrosine, phenylalanine, creatine,2-glutaric acid, acetic acid, lactic acid, ketone and lipids were significantly different between the two groups. From CPB commencement, ATP concentration in serum was gradually reduced in two groups patients. ATP concentration had not been restored to the level before CPB in the conventional group until48h after surgery (P<0.05)while the concentrations at48h after surgery was restored to preoperative levels in beating heart group(P>0.05). From weaning from CPB to48h after weaning from CPB, ATP concentrations in serum in beating heart group were higher than those in the conventional group (P<0.05).Conclusion:The body exists a serious sugar, protein and fat metabolism disorders in patients underwent open heart surgery under CPB, and the use of NMR-based metabolomics techniques can reflect these changes. This study concludes that metabolism disorders caused by valvuar surgery is relatively small in patients with beating heart surgery. |
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