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Stady On Cardiopulmonary Bapass Induced Myocardium CPLA2-γ Activation And Its Relation With Myocardial Injury And Dysfunction

Posted on:2006-09-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:X Y WuFull Text:PDF
GTID:1104360155451079Subject:Academy of Pediatrics
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Background: The incidence of congenital heart disease (CHD) has taken the first place among cardiovascular diseases in children, which serious hinders the growth and development of the children, and has become one of the major causes of infants and young children deaths. Up to now, there have been no effective preventive methods. The major way of treatment is surgically correcting the congenital heart anormalies under Cardiopulmonary bypass (CPB). Therefore, CPB is the precondition of cardiac surgery. However, uncontrolled inflammatory factor releasing during CPB will trigger the systematic inflammatory response syndrome and resulting in multiple organ dysfunction syndrome, including cardiovascular system, respiratory system, central nervous system, urinary system, digestive system, hematological system and so on. Multiple organ failure (MOF) may be even resulted in severe patients. Although a large variety of researches have been done in animal models and clinical practices, the core mechanism of SIRS as to CPB is still not well understood and the curative effect is unsatisfactory. Thus, surgical repair of the complex CHD in infants and newborns faces great challenges. It has become an urgent issue to block the early cascade of cytokine releasing and the development of SIRS, to reduce short-term and long-term complications, to promote successful surgical repair and the value of life. Objective: We measured the serum levels of interleukin-6 (IL-6), tumor necrosis factor- alpha(TNF-α), endothelin-1(ET-1), thromboxane B2(TXB2), 6-Keto-ProstaglandinF1α(6-Keto-PGF1α), cardiac troponin I (cTnI) and MB isoenzyme of creatine kinase (CK-MB) in different times during CPB, cPLA2- γ gene expression prior and post CPB, the myocardium ultrastructure alternations, left heart systolic and diastolic function variations to investigate the mechanism of inflammatory factors releasing, myocardium cPLA2-γ activation, myocardial structure and function changes induced by CPB. Materials and Methods: 1. The blood samples were obtained 1 hour prior operation, at 30 minute during CPB, immediate past CPB, 1 hour and 24 hours after operation from 20 CHD patients undergoing open heart surgery. The serum levels of IL-6,TNF-α,ET-1,TXB2 and 6-Keto-PGF1α were determined by radio immunoassay. 2. Small pieces of right atria myocardium tissue were collected from 12 VSD patients prior and post CPB. The expression levels of cPLA2-γ gene were detected by RT-PCR and analyzed with gel image analysis software.The myocardial ultrastructure was observed under Electron microscope. 3. The serum samples were obtained prior CPB, 1 hour after CPB and 7 days post heart operation in 20 patients with CHD. The cTnI and CK-MB concentrations were measured with immunochromatographic method and UV-test. The major left ventricular systolic function parameters, including LEVF, LVFS and CO were calculated by measurement of the LVDD, LVDS, LVSV and LVDV through two dimensional transthoracic echocardiography. The left ventricular diastolic function criteria include E-peak, A-peak, E/A ratio and IVRT were measured through mitral orifice blood flow spectra with Doppler. 4. The results are expressed as -x±s. The values were compared by t test and p< 0.05 was considered statistically significant. Results: 1. There were no significant changes in serum IL-6 and TNF-α levels during CPB (P>0.05). The serum ET-1 levels increased significantly 1 hour after CPB (P<0.05). The serum levels of TXB2, 6-Keto-PGF1αwere significantly increased at 30 minute during CPB and kept in high levels till the end of the CPB (P<0.05), then decreased rapidly in 1 hour and 24 hours after CBP. There were no significant changes in TXB2 / 6-Keto-PGF1αratio during CPB(P> 0.05). 2. The myocardium cPLA2-γ gene expression levels after CPB were increased significantly(P<0.05). The myocardial ultrastructuraldegenerations after CPB include hypertrophy of nucleus,swelling under plasma membrane, Chromatin margination and dilatation of smooth endocytoplasmic reticulum in myocardial cell...
Keywords/Search Tags:cardiopulmonary bypass, inflammatory factors, cytosolic phospholipase A2, ultrastructure, heart function
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