The Effect Of The Intervention With Unfractionated Heparin (UFH) Or Low Molecular Weight Heparin (LMWH) On Fluid-resuscitated Sepsis Rats

Sepsis has become a huge disease burden in today's world.Although human have got a deep insight into the pathogenesis of sepsis,there are few effective remedies yet.Since 1990's,anticoagulants have aroused a comprehensive interest in the field of sepsis research,which is a result of the achievement that more and more knowledge about the crosstalk between inflammation and coagulation has been obtained.Unfortunately rhAPC is the only anticoagulant recommended by SSC in 2008 as a remedy to improve the survival of patients with severe sepsis.As for heparin,there have been too much debate on the issue of whether such a cheap anticoagulant has the same power as,if not more than,rhAPC to treat sepsis patients,and whether it can improve tissue oxygenation among the sepsis victims.In this article,the assessment of the sepsis rats treated by unfractionated heparin(UFH) about their 7 days' survival after CLP operation was made in the first part, then organ damage,tissue oxygenation,and histopathology of the sepsis rats treated by UFH or LMWH at the time point of 36 hours after CLP operations were implored in the second part.Section 1 The Effect of unfractionated heparin(UFH) with 3 kinds of dosage on the survival of the sepsis rats during the 7 days after CLP operation.Objective:To evaluate the effect of different dosage of UFH on the 7 days' survival of the rats after CLP operations.Methods:24 S-D rats were equally allocated into 4 groups at random.Each group received an unique remedy at the time of 12 hours after CLP operations.These remedies comprise a baseline fluid resuscitation(BFR) and three kinds of UFH interventions with different dosage.During the 7 days after CLP operation,all rats' physical activity and the number of deaths were observed and recorded at 12 hour intervals.All rats underwent autopsy within 8 hours after death.Results:At the time of 144 hours after CLP operation the numbers of survivors of group A,B,C,D are 0,0,2,4 respectively.Statistical analysis of survival rate during 120 hours after CLP operation shows no difference among all groups(P＜0.05),but Log-rank test shows statistical difference of survival curve between two pairs of groups,i.e.group A and D,group B and D.Conclusion:Compared with the BFR intervention and the UFH(300IU/KgBW/d) intervention,the intervention with UFH(1500IU/KgBW/d) can significantly improve the survival of sepsis rats during the 7 days after CLP operations.This benefit may have a positive relevance with the dosage of UFH.Section 2 The influence of the intervention with unfractionated heparin or low molecular weight heparin on the changes of organ function,tissue oxygenation,and histology of the sepsis rats at the time of 36 hours after CLP operations.Objective:To evaluate the influence of the intervention with unfractionated heparin or low molecular weight heparin on the changes of organ function,tissue oxygenation,and histology of the rats at the time of 36 hours after CLP operations.Methods:24 S-D rats were equally allocated into 4 groups at random.Each group received an unique remedy at the time of 12 hours after CLP operations.These remedies comprise a BFR,an intervention with UFH(250IU/KgBW/4h) and an intervention with LMWH(250AXaIU/KgBW/4h).At the time of 36 hours after CLP operations,the parameters of organ function and tissue oxygenation of the sepsis rats were monitored. Afterwards,the rats were killed and fresh liver,kidney,and lung sections were harvested and fixed in 10%buffered formalin.Results:1.Compared with group E,the other 3 groups show significant increase in the value of ALT, BUN,Scr,Lac,Pa-vO₂,O₂ER and significant decrease in the value of ScvO₂. (P＜0.05)2.Compared with group F,group G shows significant increase in the value of PaO₂, Pa-vO₂,,O₂ER and significant decrease in the value of ScvO₂.,Lac.(P＜0.05)3.Group H shows no statistical difference with group F in the value of ALT,BUN,Scr, PaO₂,Lac,PH,Pa-vO₂,O₂ER,ScvO₂.(P＜0.05)Conclusion:1.The rats will develop into the phase of severe sepsis at the time of 36 hours after CLP operations,manifesting organ damage and poor tissue perfusion.2.Compared with the intervention of solitary BFR,the UFH(250IU/KgBW/4h) intervention combined with BFR can significantly increase oxygen extraction ratio(O₂ER) of sepsis rats with a lower level of anaerobic metabolism.3.At the time of 36 hours after CLP operations,among the sepsis rats undergoing the combined intervention of UFH(250IU/KgBW/4h) and BFR,O₂ER manifests a positive relevance with the anticoagulative intensity of UFH.4 No evidence demonstrates that the LMWH intervention(250AXaIU/KgBW,SC,q4h) combined with BFR is superior to the solitary BFR intervention to increase O₂ER of and to alleviate organ damage of sepsis rats at the time of 36 hours after CLP operations.5 Compared with the combined intervention of LMWH(250AXaIU/KgBW,SC,q4h) and BFR,the combined intervention of UFH(250IU/KgBW/4h) and BFR can significantly increase oxygen extraction ratio(O₂ER) of sepsis rats at the time of 36 hours after CLP operations.