| Intestinal ischemia frequently occurs in clinical states,such as hemorrhagic shock and trauma,associated with the development of multiple organ failure.’ Because loss of gut barrier function and the subsequent translocation of bacteria and endotoxin have been documented in conditions associated with intestinal ischemia,loss of gut bafrier function has been proposed as a major contributor to the systemic immunoinflammatory response that ultimately leads to multiple organ failure.Traditional resuscitation strategy fails to treat and in fact worsens the hypothermia,acidosis,and coagulopathy that are associated with severe trauma has been recently noted by several authors,including surgeons deployed in the global war on terrorism.An alternative strategy,aptly named "damage control resuscitation" to emphasize its pairing with damage control surgical techniques,is described and is currently in use in Iraqi war.This strategy includes the tolerance of moderate hypotension(systolic blood pressure approximately 90 mm Hg);the trauma system-wide emphasis on the recognition and prevention of hypothermia;the temporization of acidosis(or at least prevention of worsening acidosis);and the emphasis on immediate correction of coagulopathy as the most treatable arm of the "lethal triad." The treatment of coagulopathy features appropriate choices of resuscitation fluids;the amounts and ratio of these products to one another;the timing of the delivery of these products;and the use of adjuncts to resuscitation(for example,recombinant Factor Ⅶa).Clearly,for this resuscitation strategy to be successful,it must be married to the treatment of immediately life-threatening conditions(for example,tension pneumothorax)and the rapid surgical control of hemorrhage.In our study,we choose swine grade IV liver injury models to receive damage control resuscitation.The tight junction of intestinal epithelial cells were examined before and after resuscitation,in order to demonstrate the alternation of intestinal mechanism barrier function and the mechanism of enterogenic infection after damage control resuscitation.It could provide theoretical support for protection of intestinal barrier fucntion and avoidance of coagulopathy after trauma.Chapter 1:Effects of triptolide on the development of chronic colitis in IL-10 deficient miceObjective:To establish a model of critical liver trauma of great fidelity and repeatability and perform DCS on this basis.Methods:Young pigs were injured by NS301C semi-automatic repeating nail gun adapted impinge in the left medial lobe of the liver and DCS was performed:abdominal packing and temporary abdominal closure.Observation indexes include injury evaluation,24-hour postoperative survival rate,hemostatic effect,blood loss,transfusion quantities,vital signs and their recovery time,blood routine,coagulation function and blood gas analysis.Results:Analysis of traumatic condition accorded with AAST grade IV hepatic injury and no adjacent organs were injured.After DCS,24-hour postoperative survival rate was 91.7%(11/12),with no obvious wound errhysis.Normal blood pressure could be better kept.After injury,body temperature,blood pressure,arterial PH,prothrombin time,AST,ALT and Cr could quickly return to their normal levels.Conclusion:We successfully establish a reproducible piglet model of level IV liver injury according AAST system.The model is consistent with clinical blunt liver injury,and can mimic the typical pathophysiological changes of "severe trauma-massive hemorrhage-lethal triad".The strategy of DCS,i.e."initial abdominal packin,rapid operation-ICU resuscitation-reoperation",can effectively improve each physiological parameter,and finally improve the prognosis of this animal model.Chapter 2:Effects of Permissive Hypotensive Resuscitation on Intestinal Mucosal Barrier in Severe Abdominal TraumaObjective:To explore the effects of permissive hypotensive resuscitation on hemodynamics,coagulation function and intestinal mucosal barrier and provide basis for reasonable target blood pressure for resuscitation.Methods:12 female native pigs randomized equally to 2 groups:the permissive hypotensive resuscitation group and the standard blood pressure resuscitation group.Severe abdominal trauma model and DCS were performed as Part One.Observation indexes include 72-hour survival rate,hemodynamic indexes,coagulation function,bacteria culture of mesenteric lymph nodes and liver tissues,endotoxin test of portal vein blood,histopathological examination and transmission electron microscope(TEM)of terminal ileum and examination on expression of tight junction proteins.Results:Survival rate of the permissive hypotensive resuscitation group was remarkably higher than that of the standard blood pressure resuscitation group.Hemodynamic indexes of the permissive hypotensive resuscitation group were preserved in a relatively normal range,whereas explicit acidosis appeared in the standard blood pressure resuscitation group.Thrombelastogram(TEG)suggested that coagulation function of the permissive hypotensive resuscitation group was apparently better than that of the standard blood pressure resuscitation group.Bacteria culture and endotoxin test of the permissive hypotensive resuscitation group at all time points were obviously lower than that of the standard blood pressure resuscitation group.Expression of tight junction proteins of the permissive hypotensive resuscitation group at all time points was also noticeably better than that of the standard blood pressure resuscitation group.Conclusion:Application of permissive hypotensive resuscitation in severe abdominal trauma distinctly improved survival rate,respiratory and circulatory function and coagulation function during resuscitation,as well as reduced the risk of acidosis,bacteria and endotoxin translocation,which may benefit from better protection of intestinal mucosal barrier.Chapter 3:Effects of Blood Products in Different Ratios on Intestinal Mucosal Barrier in Severe Abdominal Trauma ResuscitationObjective:To explore effects of blood products in different ratios(FFP:RBC)on hemodynamics,coagulation function,and intestinal mucosal barrier and provide basis for rational application of blood products in severe abdominal trauma resuscitation.Methods:24 female native pigs were equally randomized to 4 groups:the whole blood group,the 1:1 group,the 1:2 group and the 1:3 group.Permissive hypotensive resuscitations were performed in all the four groups.Severe abdominal trauma model and DCS were performed as Part One.Observation indexes include 72-hour survival rate,hemodynamic indexes,coagulation function,bacteria culture of mesenteric lymph nodes and liver tissues,endotoxin test of portal vein blood,histopathological examination and transmission electron microscope(TEM)of terminal ileum and examination on expression of tight junction proteins.Results:No differences were showed in survival rate and hemodynamic indexes of the four groups.TEG suggested that in the 1:3 group,both R value and K value clearly lasted longer and a angle was distinctly smaller,compared with other groups;MA value of the whole blood group was greater than the other groups.Bacteria culture and endotoxin test at all time points showed no marked difference between the four groups.Routine pathological results indicated that intestinal mucosae were severely damaged at the beginning of resuscitation in all the four groups and injury scores reached their highest at 12h.Pathological evaluation and expression of tight junction proteins at all time points showed no significant difference between the four groups.Conclusion:Compared with the 1:3(FFP:RBC)group,the 1:1 and 1:2 groups could distinctly improve coagulation.Maximum amplitude and stability of blood clots in the whole blood group were better than other groups,in which platelets played a vital part.No distinct differences were found in intestinal mucosal barrier between the groups,reflected in expression of tight junction proteins,bacteria and endotoxin translocation.SummaryDuring the fluid resuscitation of severe abdominal trauma,maintainance of MAP level at 60mmHg significantly reduced the chances of metabolic disorders and acidosis,effectively improved coagulation function,and reduced the risk of hemorrhage,hence higher survival rate.Intestinal barrier functions were effectively protected and thus less bacteria and endotoxin translocation.Compared with the 1:3(FFP:RBC)group,the 1:1 and 1:2 groups could distinctly improve coagulation function and thus reduced the risk of hemorrhage.Platelets played a vital part in maximum amplitude and stability of blood clots,hence rational application of platelet concentrates during resuscitation.Blood products in different ratios exert no significantly different effects on intestinal mucosal barrier.Therefore,greater effects on intestinal barrier may result from target blood pressure. |
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