Experimental Study Of Adjunct Peritoneal Resuscitation On Hemorrhagic Shock In Rats

Background Today the major clinical therapeutic methods for trauma-hemorrhagic shock are controlling of bleeding and rapid correcting of intravascular volume by intravenous infusion. However, refractory hypotension during the process of resuscitation and the complications after resuscitation such as systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) are still tough problems for the treatment of trauma-hemorrhagic shock.Studies have already confirmed that gut barrier dysfunction plays an important role during the progress of hemorrhagic shock. During shock mesenteric blood vessel convulsion and hypoperfusion and its sequale of ischemia result in impairment of gut barrier. And as a consequence the bacteria/endotoxin translocated to circulation. They aggravate injury caused by ischemia and lead to SIRS and MODS. Some therapeutic strategies to prevent gut injury or dysfunction including selective gut decontamination, enteral nutritional regimens, improving blood flow of visceral and preventing toxic mesenteric lymph entering into circulation have been attempted. However, the methods are not well clinically applied. Recently researchers of Louisville veterans affairs medical center introduced a new resuscition method, adjunct peritoneal resuscitation (PR) for hemorrhagic shock.This technique uses a clinical peritoneal dialysis solution injecting to abdominal cavity at the time of conventional resuscitation(CR) to dilate mesenteric mircocirculation. To date this technique is on the way of its initial exploration and its effects and molecular mechanisms need further inv(?)stigation. In this study severe trauma-hemorrhagic rat shock model was used to evaluate its effect. And its mechanisms were explored from mesenteric microcirculation and mesenteric lymph route. And its influences to some important organs were also evaluated.Objective To evaluate the therapeutic effects of adjunct PR on severe hemorrhagic shock in rats and its influence on the functions and structure of some important organs of shock rats and for the further to explore its mechanism from mesenteric microcirculation and lymph routes.Methods1. Severe hemorrhagic shock rats model was established. Male SD rats were divided into 4 groups:Sham group (SS),②hemorrhagic shock with CR (HS+CR),③hemorrhagic shock with CR (HS+CR+PR),④emorrhagic shock with no resuscitation (HS). Arterial PH,LA,GLU and TGF-αwere determined at equilibrium,before resuscitation and 2h after resuscitation. The survival time were recorded.2. Hemorrhagic shock model was established. The rats were divided into 3 groups:HS,HS+CR and HS+CR+PR group. Blood concentrations of LD,CK,ALT,AST,Urea,Cre were determined by automatic biochemical analyzer 2h after resuscitation. Tissue structural changes of lung, liver, heart and kidney were analysed.3. Hemorrhagic shock model was established. Mesenteric circulation in vivo were observed 2h after resuscitation. Mesenteric microvascular diameter and blood flow in intestinal wall was measured.The numbers of neutrophils adherent to veinules were accounted. A segment of the terminal ileum was harvested at death and processed for evaluation of mucosal injury and water content.4. Hemorrhagic shock model was established. The rats were divided into six groups as follows:①SS group②SS+CR group③SS+CR+PR group④HS group⑤HS+CR group⑥HS+CR+PR group.Two hours after resuscitation mesenteric lymph was collected by laparotomy. Bioactivity of mesenteric lymph was tested by lymph mediated neutrophils burst activity and HUVECs injury. Three hours aftrer resuscitation pulmonary microvascular permeability was investigated.Results1. Compared with HS+CR group, MAP in HS+CR+PR group was significantly improved 2h after resuscitation. And blood concentrations of LA and TGF-αin HS+CR+PR group were significantly decreased. Arterial PH in HS+CR+PR group was significantly improved. Survival to 72h in HS+CR+PR group was 58.3%, significantly higher than that in HS+CR group (8.3%) (P<0.05)2. Compared with HS+CR group, Blood concentration of ALT. AST,Urea,Cre. LDH and CK in HS+CR+PR group were all significantly decreased 12h after resuscitation. Histological evaluation revealed tissue injury of lung,live,heart and kidney in HS+CR+PR group were significantly decreased.3. Mesenteric microcirculation revealed that blood flow of arterioles and veinules in HS+CR+PR was slower than that in HS+CR group. And there were less neutrophils adherent to veinules in HS+CR+PR group. The diameters of arterioles and venules in HS+CR+PR group were 1.41 fold and 1.80 fold to those in HS+CR group respectively. Water content and ileum injury in HS+CR+IR group were both greatly decreased.4. Compared with HS+CR group, mesenteric lymph flow in HS+CR+PR group was greatly impoved. Shock lymph mediated neutrophils respiratory burst activity and HUVECs injury in HS+CR+PR group was significantly decreased and pulmonary microvascular permeability in HS+CR+PR group was also decreased.Conclusion1. Adjunct PR with 2.5% peritoneal dialysis solution can better improved MAP,decrease concentrations of LA,TGF-αand attenuate acidosis. Adjunct PR can also achieve a better long time survival of severe hemorrhagic shock in rats.2. Compared with CR, adjunct PR can usefully decrease LDH,CK, ALT, AST, Urea, Cre concentrations in blood of shock rats,ameliorate hear,liver and kidney function and relieve tissue injury of lung,heart,liver and kidney.3. The mechanism of adjunct PR may be that it ameliorates mesenteric microcirculation, proctects gut barrier and decrease bioactivity of mesenteric lymph of shock rats.