Study Of Open Abdomen Treatment Of Liver Dysfunction In Intra-abdominal Infection With Intra-abdominal Hypertension

Sepsis is a considerable health problem and a leading cause of death in many intensive care units. Current knowledge implies that Sepsis is a clinical condition caused by the immune response of a host to infection or trauma, which is characterized by systemic inflammation and coagulation abnormalities. It can range in severity from a systemic inflammatory response to organ dysfunction, multiple organ failure, and ultimately, death. Sepsis can develop from, but is most commonly associated with severe abdominal or lung infections such as pneumonia. People with a compromised immune system are especially prone to septic shock. Such patients include those with autoimmune deficiency syndrome, those receiving cancer treatments, the very young, and the very old.Abdominal compartment syndrome (ACS) is defined as "a sustained IAP>20mmHg (with or without an APP<60mmHg) that is associated with new organ dysfunction-failure". Abdominal compartment syndrome results in impairment of cardiovascular, respiratory, gastrointestinal, genitourinary, and central nervous system functions. Intra-abdominal pressure and increased intra-abdominal pressure was initially described in the18th century. The importance of ACS has been well documented in last20years since the introduction of laparoscopy. Abdominal trauma, intra-abdominal infection, pancreatitis, an accumulation of blood in the abdominal cavity, and retroperitoneal hematomas with massive fluid load may all contribute to increased intraabdominal pressure and ACS.Toll-like receptors (TLRs) as pattern recognition receptors are part of the innate immune system. The most important and best characterized ligand for Toll-like receptor4(TLR4) is exogenous lipopolysaccharide (LPS), the principle glycolipid component of the outer-membrane of Gram-negative bacteria. LPS adapts via serum and cell-surface proteins including LPS binding protein (LBP) and CD14, to the TLR4/myeloid differentiation2(MD2) signaling complex. TLR4is strictly dependent upon the presence of MD2, a small cysteine-rich glycoprotein, that binds to the ectodomain of TLR4and to LPS. The engagement of TLR4by microbial products leads to intracellular recruitment of adapter proteins including myeloid differentiation protein88(MyD88), TIR-associated protein (TIRAP), TIR-domain-containing adaptor inducing-IFN-β(TRIF), and TRIF-related adaptor molecule (TRAM). The MyD88dependent signaling pathway results in phosphorylation and activation of the IμBa kinase (IKK) complex. The cytoplasmic inhibitor IκB is phosphorylated which leads to its degradation and the release of NF-κB into the nucleus where it activates many inflammatory genes. In addition, mitogen activated protein kinases (MAPK) p38and c-Jun N-terminal kinase (JNK) are activated resulting in the phosphorylation of API which is also critical for the induction of cytokine genes.The open abdomen is now a common clinical challenge in surgical intensive care units (SICU). It is an iatrogenic complication of modern surgery, resulting from advances in the operative management of trauma, severe infection, and other abdominal emergencies. Occasionally, patients require open abdomen management because of necrotizing abdominal wall infections. Perhaps the most common indication for the open abdomen is "damage control" laparotomy for abdominal trauma. The initial goals are to hemostasis and control of spillage, followed by expeditious transfer of the patient to the SICU for restoration of the physiologic envelope, and a subsequent planned reoperation. The use of the open abdomen in patients with acute mesenteric ischemia is based on the need for a mandatory "second look" to assess bowel viability and resect additional ischemic segments if necessary. Our study is to evaluate the open abdomen management and closed management treatment of liver injury after the onset of sepsis and abdominal compartment syndrome (ACS) in rats.Part1:Study of the Mechanism of Liver Injury In Sepsis And Abdominal Compartment SyndromePurpose. To evaluate the extent of liver injury after the onset of sepsis and abdominal compartment syndrome (ACS) in rats.Methods. We divided SD rats into four groups of24.Group1was the sham group. In group2, sepsis was induced by cecal puncture and ligation; in group3, ACS was created by placing a catheter in the abdominal cavity; and in group4, both sepsis and ACS were induced simultaneously. After operation or sham-operation, at1h,6h,12h,24h killed the rats(each point6).Liver sections stained with hematoxylin-eosin were assessed pathologically, and liver injury was defined by the following four pathological patterns:spotty necrosis, portal inflammation, ballooning degeneration, and steatosis of the liver. We used "Hepatic Injury Severity Scoring"(HISS) to evaluate the liver injury in sepsis, ACS, and sepsis plus ACS. Blood was collected for liver function tests. The expressions of Toll-like receptor4(TLR4), TNF-a and IL-6of rat livers were examined by reverse transcription-polymerase chain reaction (RT-PCR). And the expression of IκBa of rat livers were examined by western blot.Results. We found TNF-a and IL-6concentrations, TLR4expressions, IκBa degradation in rat liver were increased.At24h after operation, there were significant differences in histopathologic grade between group1and groups2,3, and4(P<0.05). Aspartate aminotransferase, alanine aminotransferase levels, TNF-a and IL-6concentrations, TLR4expressions, IκBa degradation were significantly higher in group4than in the other three groups.Conclusions. The findings of this study showed that liver function severely affected the onset of ACS and sepsis. The liver injury resulting from sepsis plus ACS is more severe than that resulting from either one independently.Part2:Study of Open Abdomen treatment of Liver Dysfunction in Intra-abdominal Infection with Intra-abdominal HypertensionPurpose. To evaluate the open abdomen management and closed management treatment of liver injury after the onset of sepsis and abdominal compartment syndrome (ACS) in rats.Methods. We randomized divided the sepsis and ACS rats into two groups. Group1accepted closed management, the other group used the open abdomen management. After operation, at1h,6h, Id,3d,5d,7d killed the rats(each point6).Liver sections stained with hematoxylin-eosin were assessed pathologically, and liver injury was defined by the following four pathological patterns:spotty necrosis, portal inflammation, ballooning degeneration, and steatosis of the liver. We used "Hepatic Injury Severity Scoring"(HISS) to evaluate the liver injury. Blood was collected for liver function tests. The expressions of TLR4, TNF-a, IL-6, STAT3and SOCS3of rat livers were examined by reverse transcription-polymerase chain reaction (RT-PCR). And the expression of IκBa of rat livers were examined by western blot.Results. The early stage after closed or open abdomen, TNF-a and IL-6concentrations, STAT3expressions, IκBa degradation in rat liver were higher in open abdomen rats than the closed management ones(P<0.05). TLR4and SOCS3expressions were lower in open abdomen rats than the closed management ones(P<0.05). Aspartate aminotransferase, alanine aminotransferase levels also was lower in open abdomen ones(P<0.05).Conclusion. This randomized study demonstrates that open abdomen management could improve liver regeneration in the early stage after operation. Also open abdomen could reduce inflammatory response by reducing TLR4expressions.SummarySepsis and ACS could improve TLR4expression and IκBa degradation in the liver, so the liver function could be severely affected, sepsis plus ACS is more severe than that resulting from either one independently. Open abdomen could improve liver regeneration by improving TNF-a and IL-6concentrations, STAT3expressions, IκBa degradation and reducing SOCS3expressions in the early stage after operation. Also open abdomen could reduce inflammatory response by reducing TLR4expressions.