A Novel Intra-abdominal Hypertension Model After Trauma-hemorrhagic Shock And Its Application

Background：Initial fluid resusucitation is an effective treatment for trauma-hemorrhagic shock.Hemorrhagic shock,followed by massive fluid resuscitation with the hallmark of increasedvascular permeability,"third space"of fluid and generalized edema,will result in increase ofintra-abdominal pressure(IAP), and finally intra-abdominal hypertension(IAH).IAH,though occurred in abdomen,has a/an direct or indirect impact on every organsystem in the body,and causes increased mortality. The purpose of this study was to build astable and low-cost model of secondary IAH in rats that was induced by massive crystalloidresuscitation after trauma-hemorrhagic shock,and to study the impact of different resusucitativefluids on IAP and organs function through this model,hoping to offer suggestions for theappropriate application of fluids for the resusucitation of trauma-hemorrhagic shock.Methods：1. Building a novel secondary IAH model after trauma-hemorrhagic shock in rats:A totalof32Sprague–Dawley rats (230-240g)were randomized into four groups: Group I: the ratswere exsanguinated to a mean arterial pressure(MAP) of40mmHg, hemorrhagic shock wasinducedand maintained for1hr, and portal hypertension by partial ligation of the portal veinwas induced1hr later; Group II: after inducing portal hypertension, hemorrhagic shock wasinduced with a MAP of40mmHg and maintained for1hr; Group III: after inducing portalhypertension, hemorrhagic shock was induced with a MAP of40mmHg and maintained for2hrs; Group IV: after inducing portal hypertension, hemorrhagic shock was induced with aMAP of40mmHg and maintained for2hrs, and a specially designed abdominal restraintdevice was used. After the above procedures, the collected blood was reinfused,and lactatedRinger’s solution was continuously infused at a rate of30ml/h until the secondary IAH modelwas established(IAP>12mmHg). MAP, inferior vena cava pressure(IVCP), time spent,infusion volume and urine output were recorded throughout the experimental process,and the wet to dry weight ratios of the organs were also analyzed. Abdominal contrast-enhancedcomputed tomography (CT) scans were performed on the models when the IVCP was0mmHg,4mmHg,8mmHg,and12mmHg.2. Studying the relationship between different fluids resusucitation and the occurance ofIAH: A total of24Sprague–Dawley rats (230-240g)were used.After inducing portalhypertension, hemorrhagic shock was induced with a MAP of40mmHg and maintained for2hrs,and a specially designed abdominal restraint devices were used. After procedures aboverespectively, the collected blood was reinfused.Then the rats were randomized into threegroups:LR group, lactated Ringer’s Solution group(LR only,30ml/h); HS group,7.5%hypertonic saline group(first HS，6ml/kg，0.5ml/min，and then LR，30ml/h);HES group,6%hydroxyethyl starch(130/0.4) group(first HES，30ml/kg，0.3ml/min，and then LR，30ml/h).Success rate of developing IAH, MAP, IVCP, time spent, infusion volume and urine outputwere recorded throughout the experimental process, and alanine aminotransferase (ALT)、aspartate aminotransferase(AST), urea solution(Urea)、 creatinine(Cr), diamine oxidase(DAO)、D-lactic Acid(D-LAC), the wet to dry weight ratios of the organs were also analyzed.Results：1. The rats in Group I all died after portal vein ligation. No models were constructed inGroups II or III. A single rat died in Group IV after portal ligation,but the remaining rats allsuccessfully developed IAH. The success rate was87.5%.2. In LR group,one rat died after portal ligation,but the remaining rats all successfullydeveloped IAH. The success rate was87.5%. During the resusucitation period,the averagetime was5.26±0.59hrs, the average total infusion volume was665.5±86.04ml/kg,and theaverage life time was4.67±2.74hrs after IAH was achieved. In HS group,only one ratsuccessfully developed IAH,the rest all died during the resusucitation period. The success ratewas12.5%. During the resusucitation period,the average time was6.27hrs, the infusion ofHS was1.41ml/kg and the average total infusion of LR was800.1ml/kg. The average lifetime was8.5hrs after IAH was achieved.In HES group, two rats successfully developedIAH,the rest all died during the resusucitation period.The success rate was25%. During theresusucitation period,the average time was7.32±0.21hrs, the infusion of HES was7.16±0.02ml/kg and the average total infusion of LR was899.3±29.95ml/kg. The average life time was9.05±0.35hrs after IAH was achieved. In LR group,HS group,HES group, results of ALT were 165.6±46.0U/L,127.7±39.5U/L and139.7±48.6U/L； results of AST were274.0±56.1U/L,176.2±39.6U/L,227.1±53.0U/L；results of Urea were8.33±1.39mmol/L,5.68±1.09mmol/L,6.48±1.01mmol/L；resultsofCr were250.7±57.3μmol/L,106.4±30.1μmol/L,176.63±46.9μmol/L；results of DAO were4.61±0.81U/ml,3.04±0.38U/ml,3.98±0.33U/ml；results of D-LAC were2.90±0.31mg/ml,1.88±0.34mg/ml,2.30±0.40mg/ml。Conclusions：1. A stable and low-cost rat model of secondary IAH was successfully established byresuscitation after a combination of inducing portal hypertension, hemorrhaging to a MAP of40mmHg for2hrs and applying an abdominal restraint device, all of which mimic keyetiological factors for the development of secondary IAH.2. Resususcitation by hypertonic saline or hydroxyethyl starch(130/0.4) combined withlactated Ringer’s Solution could reduce the occurrence of IAH,and reduced the impairment ofliver、kidney and intesinal.