Assessment To Systemic Inflammatory Response Syndrome In The Ovine Fetus By Doppler Ultrasound And Exploration To Its Possible Mechanism

Objective To evaluate the changes of hemodynamic during fetal inflammatory response syndrome(FIRS) period by Doppler ultrasound,and assess the corrlation between hemodynamic paratmeters and fetal plasma TNF-αand IL-6 concentration, and explore its possible mechanism in fetal cardiac function.Methods 22 near-term pregnant sheep were used in this study,Uuder ultrasound guidance,10 animals were performed with LPS-cordocentesis,7 animals were performed with LPS-amniocentesis and another 5 animals as a control group.In experiment groups animal,LPS was injected into the umbilical cord vein(10μg/kg of fetal body weight) and amniotic cavity(200μg/kg of maternal body weight) at 120(range 116-130) days gestation(term=145 days ),respectively.Doppler echocardiography were performed at different time during LPS administration.Fetal umbilical cord blood samples were collected and measured for TNF-α,IL-6,MDA and cTnI.The correlation coefficient was calculated to established the relationship between the TNF-α,IL-6 concentation and Doppler scanning values.The mRNA of Fas and protein of nuclear factor-K B p65(NF-κB p65 ) and caspase3 of fetal myocardium were examined with immunohistochemistry.Results 1.After LPS administration,the fetal plasma TNF-α,IL-6 level significantly increased with time(P<0.05),and still significantly increased as compared with the control animals(P<0.05).2.In the peripheral vessels,the fetal umbilical artery (UmA),renal artery(RA),ductus venous(DV) waveform pulsatility index(PI) values significantly increased with time(P<0.05),and still significantly increased as compared with the control animals(P<0.05).However,the fetal middle cerebral artery(MCA) PI values significantly reduced with time(P<0.05),and still significantly reduced as compared with the control animals(P<0.05).3.In the cardiac function values,left and right ventricle(LV,RV) Tei indices significantly increased with time(P<0.05),and still significantly increased as compared with the control animals (P<0.05),however,LV ejection fraction(EF),RV EF,tricuspid valve(TV) E/A ratio and mitral valve(MV) E/A ratio significantly increased and thus reduced(P<0.05),and still significantly different as compared with the control animals(P<0.05).4.There were significantly positive correlation between UmA PI,RA PI,DV PI,LV Tei index, RV Tei index and TNF-α(r=0.724,r=0.668,r=0.784,r=0.765,r=0.683,P<0.01) and IL-6(r=0.771,r=0.760,r=0.823,r=0.805,r=0.749,P<0.01 ).There were significantly negative correlation between MCA PI and TNF-α,IL-6(r=-0.727, r=-0.728,P<0.01 ).And there were no correlation between LV EF,RV EF,TV E/A ratio,MV E/A ratio and TNF-α(r=-0.195,r=-0.157,r=-0.204,r=-0.156, P>0.05) and IL-6(r=-0.157,r=-0.128,r=-0.199,r=-0.228,P >0.05).5.After LPS administration,the fetal plasma MDA,cTnI level significantly increased with time(P<0.05),and still significantly increased as compared with the control animals (P<0.05).6.FIRS could upregulating the express of Fas mRNA,enhancing the protein quantity of NF-κB p65,increasing the express of caspase3 in fetal myocardium(P<0.05),and still significantly different as compared with the control animals(P<0.05).Conclusions 1.Mostly Doppler parameters were significantly associated with TNF-αand IL-6 concentration.DV PI exhibits the strongest relationship in peripheral vessels,and Tei index exhibits the strongest relationship in cardiac function values,respectively.Therefore,DV PI and Tei index might be an useful quantitative parameters for assessing FIRS.2.Apotosis of myocardial cell might be associated with cardiac dysfunction.