Biochemical Changes in Experimental Rat Model of Abdominal Compartment Syndrome.

BACKGROUND: Increased intra-abdominal pressure (IAP) causes tissue ischemia, subsequent hypoxia, and impairment of normal tissue metabolism. Elevation of IAP above 20 mmHg leads to progression of abdominal compartment syndrome (ACS) that is associated with organ dysfunction or failure not previously manifested. AIM: To evaluate the eff ects of diff erent grades and time of exposure to IAP on biochemical parameters and oxidative stress in organs aff ected by ischemia using previously developed rat model. RESULTS: Three experimental groups exposed to diff erent IAP and time frames were tested for liver, kidney, and pancreas injury by measuring the activities of tissue specifi c enzymes in blood serum. Elevated activities of aspartate aminotransferase, pancreatic amylase, lipase, and higher concentrations of D-lactate, urea, and creatinine were found in some of the experimental groups compared to a control group of animals not subjected to increased IAP. Increased levels of biomarkers of oxidative stress as well as decrease in concentration of the major cellular antioxidant glutathione indicated the presence of oxidative injury as a result of elevated IAP. CONCLUSIONS: The developed rat model is appropriate to study the mechanism and manifestation of tissue injury during diff erent grades of elevated IAP but also to test approaches aimed to attenuate the detrimental eff ects of ACS. This study also underlines the necessity of using not a single but a set of biochemical parameters in order to assess the severity of tissue injury during elevated IAP and progression to ACS.

The Effect of Elevated Intra-Abdominal Pressure on TLR4 Signaling in Intestinal Mucosa and on Intestinal Bacterial Translocation in a Rat.

BACKGROUND: Recent evidence suggests that elevated intra-abdominal pressure (IAP) may adversely affect the intestinal barrier function. Toll-like receptor 4 (TLR-4) is responsible for the recognition of bacterial endotoxin or lipopolysaccharide and for initiation of the Gram-negative septic shock syndrome. The objective of the current study was to determine the effects of elevated IAP on intestinal bacterial translocation (BT) and TLR-4 signaling in intestinal mucosa in a rat model. METHODS: Male Sprague-Dawley rats were randomly assigned to one of two experimental groups: sham animals (Sham) and IAP animals who were subjected to a 15 mmHg pressure pneumoperitoneum for 30 minutes. Rats were sacrificed 24 hours later. BT to mesenteric lymph nodes, liver, portal vein blood, and peripheral blood was determined at sacrifice. TLR4-related gene and protein expression (TLR-4; myeloid differentiation factor 88 [Myd88] and TNF-α receptor-associated factor 6 [TRAF6]) expression were determined using real-time PCR, western blotting, and immunohistochemistry. RESULTS: Thirty percent of sham rats developed BT in the mesenteric lymph nodes (level I) and 20% of control rats developed BT in the liver and portal vein (level II). abdominal compartment syndrome (ACS) rats demonstrated an 80% BT in the lymph nodes (Level I) and 40% BT in the liver and portal vein (Level II). Elevated BT was accompanied by a significant increase in TLR-4 immunostaining in jejunum (51%) and ileum (35.9%), and in a number of TRAF6-positive cells in jejunum (2.1%) and ileum (24.01%) compared to control animals. ACS rats demonstrated a significant increase in TLR4 and MYD88 protein levels compared to control animals. CONCLUSIONS: Twenty-four hours after the induction of elevated IAP in a rat model, increased BT rates were associated with increased TLR4 signaling in intestinal mucosa.

Attenuation of Oxidative Stress by Ischemic Preconditioning in an Experimental Model of Intraabdominal Hypertension.

PURPOSE: Increased intra-abdominal pressure, as used in laparoscopic surgery or seen in intraabdominal hypertension (IAH), is associated with tissue ischemia and oxidative stress. Ischemic preconditioning (IP) is a method successfully used in liver and transplant surgery, in order to attenuate the detrimental effects of ischemia and reperfusion. In this experimental study, we tested the ability of IP to modify oxidative stress induced by extremely high intraabdominal pressures. METHODS: Twenty-five female pigs were studied and divided in three groups: a control group, a pneumoperitoneum group (with pressure of 30 mmHg), and an ischemic preconditioning group (initially subjected to preconditioning with pressure of 25 mmHg for 15 min and desufflation for 15 min and then to pneumoperitoneum as in pneumoperitoneum group). Blood samples were obtained at identical time intervals in the three groups. Total oxidative capacity, total antioxidative capacity and total nitric oxide (NO), nitrite and nitrate concentrations were measured and compared between groups. RESULTS: IP increased total antioxidative capacity (p = .045) and protective mediators like nitrite (p = .022). It was also associated with a trend toward lower levels of total oxidative capacity at the end of the abdominal desufflation period but statistical significance was not met. CONCLUSIONS: IP attenuated oxidative stress induced by IAH, mainly by increasing antioxidative capacity and the levels of protective mediators. The fact that IP was effective, even when used at extremely high levels of intraabdominal pressure, reinforces the interest on this method but further studies are needed to clarify its mechanism of action and potential clinical applications.

Intra-abdominal pressure correlates with extracellular water content.

BACKGROUND: Secondary increase in intra-abdominal pressure (IAP) may result from extra-abdominal pathology, such as massive fluid resuscitation, capillary leak or sepsis. All these conditions increase the extravascular water content. The aim of this study was to analyze the relationship between IAP and body water volume. MATERIAL AND METHODS: Adult patients treated for sepsis or septic shock with acute kidney injury (AKI) and patients undergoing elective pharyngolaryngeal or orthopedic surgery were enrolled. IAP was measured in the urinary bladder. Total body water (TBW), extracellular water content (ECW) and volume excess (VE) were measured by whole body bioimpedance. Among critically ill patients, all parameters were analyzed over three consecutive days, and parameters were evaluated perioperatively in surgical patients. RESULTS: One hundred twenty patients were studied. Taken together, the correlations between IAP and VE, TBW, and ECW were measured at 408 time points. In all participants, IAP strongly correlated with ECW and VE. In critically ill patients, IAP correlated with ECW and VE. In surgical patients, IAP correlated with ECW and TBW. IAP strongly correlated with ECW and VE in the mixed population. IAP also correlated with VE in critically ill patients. ROC curve analysis showed that ECW and VE might be discriminative parameters of risk for increased IAP. CONCLUSION: IAP strongly correlates with ECW.

Intra-abdominal hypertension--an experimental study of early effects on intra-abdominal metabolism.

BACKGROUND: The main aim of this experimental study was to investigate the early effects of intra-abdominal hypertension (IAH) on intra-abdominal metabolism and intestinal mucosal blood flow to evaluate whether metabolites can serve as markers for organ dysfunction during IAH. METHODS: A swine model was used, and the animals were anesthetized and ventilated. Fifteen animals were subjected to IAH of 30 mm Hg for 4 hr by carbon dioxide insufflation. Seven animals served as controls. Hemodynamic data, arterial blood samples, and urine output were analyzed. Intraluminal laser Doppler flowmetry measured intestinal mucosal blood flow. Glucose, glycerol, lactate, and pyruvate concentrations and lactate-to-pyruvate (l/p) ratio were measured intraperitoneally and intramurally in the small intestine and rectum using microdialysis. RESULTS: IAH lowered the abdominal perfusion pressure by 12-18 mm Hg, reduced the intestinal mucosal blood flow by 45-63%, and decreased urine output by 50-80%. In the intervention group, glycerol concentrations increased at all locations, pyruvate concentrations decreased, and the l/p ratio increased intraperitoneally and intramurally in the small intestine. Control animals remained metabolically stable. Glucose and lactate concentrations were only slightly affected or unchanged in both the groups. CONCLUSIONS: IAH reduces intestinal blood flow and urinary output and causes early metabolic changes, indicating a discrete shift toward anaerobic metabolism. Intraperitoneal microdialysis may be useful in the early detection of impaired organ dysfunction with metabolic consequences in IAH and abdominal compartment syndrome.

Abdominal hypertension and decompression: the effect on peritoneal metabolism in an experimental porcine study.

OBJECTIVE: The aim of this study was to investigate the abdominal metabolic response and circulatory changes after decompression of intra-abdominal hypertension in a porcine model. METHODS: This was an experimental study with controls. Three-month-old domestic pigs of both sexes were anesthetized and ventilated. Nine animals had a pneumoperitoneum-induced IAH of 30 mmHg for 6 hours. Twelve animals had the same IAH for 4 hours followed by decompression, and were monitored for another 2 hours. Hemodynamics, including laser Doppler-measured mucosal blood flow, urine output, and arterial blood samples were analyzed every hour along with glucose, glycerol, lactate and pyruvate concentrations, and lactate-pyruvate (l/p) ratio, measured by microdialysis. RESULTS: Laser Doppler-measured mucosal blood flow and urine output decreased with the induction of IAH and showed a statistically significant resolution after decompression. Both groups developed distinct metabolic changes intraperitoneally on induction of IAH, including an increased l/p ratio, as signs of organ hypoperfusion. In the decompression group the intraperitoneal l/p ratio normalized during the second decompression hour, indicating partially restored perfusion. CONCLUSION: Decompression after 4 hours of IAH results in an improved intestinal blood flow and a normalized intraperitoneal l/p ratio.

Intra-peritoneal microdialysis and intra-abdominal pressure after endovascular repair of ruptured aortic aneurysms.

OBJECTIVES: This study aims to evaluate intra-peritoneal (ip) microdialysis after endovascular aortic repair (EVAR) of ruptured abdominal aortic aneurysm (rAAA) in patients developing intra-abdominal hypertension (IAH), requiring abdominal decompression. DESIGN: Prospective study. MATERIAL AND METHODS: A total of 16 patients with rAAA treated with an emergency EVAR were followed up hourly for intra-abdominal pressure (IAP), urine production and ip lactate, pyruvate, glycerol and glucose by microdialysis, analysed only at the end of the study. Abdominal decompression was performed on clinical criteria, and decompressed (D) and non-decompressed (ND) patients were compared. RESULTS: The ip lactate/pyruvate (l/p) ratio was higher in the D group than in the ND group during the first five postoperative hours (mean 20 vs. 12), p = 0.005 and at 1 h prior to decompression compared to the fifth hour in the ND group (24 vs. 13), p = 0.016. Glycerol levels were higher in the D group during the first postoperative hours (mean 274.6 vs. 121.7 µM), p = 0.022. The IAP was higher only at 1 h prior to decompression in the D group compared to the ND group at the fifth hour (mean 19 vs. 14 mmHg). CONCLUSIONS: Ip l/p ratio and glycerol levels are elevated immediately postoperatively in patients developing IAH leading to organ failure and subsequent abdominal decompression.

Intra-abdominal hypertension causes disruption of the blood-brain barrier in mice, which is increased with added severe head trauma.

BACKGROUND: Although the individual effect of head trauma and intra-abdominal hypertension (IAH) causing blood-brain barrier (BBB) disruption has been studied separately, their combined effect on the integrity of BBB has not been investigated. This study examines the effects of IAH and head trauma, individually and in combination, on the permeability of the BBB in mice. METHODS: Male CD-1 mice weighing 30 to 38 g were used. Control mice were anesthetized for 4 hours. The mice in the experimental group underwent the following: (1) IAH 4 hours, (2) head trauma, and (3) combined head trauma and IAH 4 hours. IAH was induced by intraperitoneal infusion of mineral oil to a pressure of 20 mm Hg. Head trauma was induced using weight drop technique. BBB permeability was quantified using the Evans blue dye extravasation method. RESULTS: BBB permeability was higher in the mice with IAH 4 hours compared with the control group (p < 0.05), higher in the mice with head trauma compared with the control group (p < 0.05), and significantly higher than the IAH and the control groups in the mice with combined IAH 4 hours and head trauma (both p < 0.05). CONCLUSION: The disruption of BBB in mice is produced by IAH and is increased with severe head trauma.

The effects of chronically increased intra-abdominal pressure on the rabbit diaphragm.

BACKGROUND: Diaphragmatic muscular remodeling is caused by various conditions and was mainly studied in pulmonary pathologies and chronic alterations of intra-thoracic pressure. We investigate the effect of the chronically increased intra-abdominal pressure (IAP) on the diaphragm by morphological and biochemical analysis. METHODS: Thirty rabbits were divided into control and study groups. IAP was increased in group B to 12 mmHg for 2 months. The left hemidiaphragm underwent morphological, while the right underwent biochemical analysis. RESULTS: In H&E, all fibers were normal. ATPase analysis demonstrated that type I fibers show no differences between groups. Type ΙΙ(Α) were decreased (p = 0.016) while type ΙΙ(Β/X) fibers were increased (p = 0.025) in group B. Fibers with resistance to fatigue were decreased in group B (p = 0.024). In group B, biochemical activity for glutathione reductase (p = 0.004), glutathione peroxidase (p = 0.021), protein carbonylation (0.029), lipid peroxidation (p = 0.005), and balance of preoxidative-antioxidative factors (p = 0.006) was increased. CONCLUSIONS: Chronically increased IAP induces alterations to the rabbit diaphragm. Adaptation, equivalent to strenuous contraction, transforms the diaphragm to be functionally more efficient toward workload but makes it vulnerable against oxidative stress.

Risk factors and outcome of intra-abdominal hypertension in patients with severe acute pancreatitis.

BACKGROUND: Intra-abdominal hypertension (IAH) is common in patients with severe acute pancreatitis (SAP). The aim of the present study was to investigate the risk factors of IAH in SAP patients and assess the prognosis of SAP combined with IAH. METHODS: To analyze the data from patients with SAP, both univariate and multivariate logistic regression analyses were applied, using 16 indices, including age, gender, Acute Physiology and Chronic Health Evaluation II scores (APACHE II), 24 h fluid balance, hematocrit, serum calcium level, and so on. Clinical prognosis such as mortality, hospital duration, of SAP patients with or without IAH was also compared. RESULTS: First 24 h fluid balance (Odds Ratio [OR], 1.003; 95% Confidence Interval [CI], 1.001-1.006), number of fluid collections (OR, 1.652; 95% CI, 1.023-2.956), and serum calcium level (OR, 0.132; 95% CI, 0.012-0.775) were found to be independent risk factors for IAH in patients with SAP. Moreover, patients with SAP and IAH had significantly longer average length of stay, both in the hospital and in the intensive care unit, higher rates of systemic and local complications, and more invasive treatments. CONCLUSIONS: The significant risk factors for IAH in patients with SAP include 24 h fluid balance (first day), number of fluid collections, and serum calcium level. Additionally, IAH is associated with extremely poor prognosis, evidenced by high rates of mortality, morbidity, and the need for invasive interventions.

[Effect of decompression in different time on hemodynamics and oxygen metabolism of porcine model with severe acute pancreatitis combined intra-abdominal hypertension].

OBJECTIVE: To assess the effect of decompression in different time on systemic hemodynamics and oxygen metabolism in a 24 h lasting porcine model of severe acute pancreatitis (SAP) incorporating intra-abdominal hypertension (IAH). METHODS: Following baseline registrations, SAP was induced in all 18 animals. A N(2) pneumoperitoneum was used to increase the intra-abdominal pressure (IAP) to 25 mmHg (1 mmHg = 0.133 kPa) in 12 of 18 SAP animals. After 6 hours, decompression was applied in 6 of these 12 pigs and the other 6 animals received decompression at 9 h since the induction of IAH. The investigation period was 24 h. Heart rate (HR), cardiac output (CO), central venous pressure (CVP), mean arterial pressure (MAP) and pulmonary arterial wedge pressure (PAWP) were continuously recorded with the aid of Swan-Ganz catheter and electrocardiography monitor; Oxygen partial pressure of artery (PaO(2)), carbon dioxide partial pressure of artery (PaCO(2)) and central venous oxygen saturation (ScvO(2)) were measured by blood-gas analysis. Besides that, systemic oxygen delivery (DO(2)) and systemic oxygen consumption (VO(2)) were calculated according to blood-gas analysis in arterial and central venous blood. RESULTS: After decompression, HR, CO, MAP, CVP, PAWP, PaO(2) and DO(2) showed no significant differences in the 6 h group when compared to SAP pigs. In the 9 h group, however, CO decreased significantly and HR, CVP, PAWP increased significantly after decompression than SAP only animals (all P < 0.05). PaO(2), ScvO(2) and DO(2) showed lower after 3 h of decompression compared with another two groups. VO(2) increased higher in IAH groups during 6 h of experiment than SAP pigs (all P < 0.05). Then VO(2) showed a trend to fall and no differences in three groups. CONCLUSIONS: There are remarkable and relatively irreversible effects on global hemodynamics and oxygen metabolism in response to the decompression in different time after sustained IAH with the underlying condition of SAP. The results of this study are in favor of a decompression in patients of SAP with IAH in early time.

Open versus closed abdomen treatment on liver function in rats with sepsis and abdominal compartment syndrome.

BACKGROUND: Despite recent advances in understanding the mechanisms of sepsis and abdominal compartment syndrome (ACS) and of improvements in their management, the mortality rates from these conditions remain high. Few studies have compared liver injuries in patients undergoing open and closed abdomen treatment. The aim of this study was to compare the effects of open versus conservative abdominal closure approaches upon liver function using a controlled and randomized model of intra-abdominal hypertension and sepsis in a rat model. METHODS: Healthy Sprague-Dawley rats underwent cecal ligation and puncture to induce sepsis, followed by intraperitoneal injection of air to induce intra-abdominal hypertension. Twenty-four hours later, the rats were randomly divided into two groups, one (n = 36) undergoing abdominal closure and the other (n = 36) undergoing open abdomen. Rats were killed after 1 hour, 6 hours, 1 day, 3 days, 5 days, and 7 days. Liver injury was evaluated by Hepatic Injury Severity Scoring. The levels of expression of Toll-like receptor 4 (TLR4), tumor necrosis factor-α, interleukin-6, signaling transducer and activator of transcription 3 mRNA, and suppressor of cytokine signaling 3 mRNA were assayed by reverse transcription-polymerase chain reaction. RESULTS: The levels of tumor necrosis factor-α, interleukin-6, and signaling transducer and activator of transcription 3 mRNA were higher, and those of TLR4 and suppressor of cytokine signaling 3 mRNA were lower, in the open than in the closed group (p < 0.05 each). Serum concentrations of aspartate aminotransferase and alanine aminotransferase were also lower in the open group (p < 0.05 each). CONCLUSIONS: Open abdominal management may improve liver regeneration soon after surgery, as well as reducing inflammatory responses, by reducing TLR4 expression.

[Open abdomen management treatment of liver injury in rats with abdominal compartment syndrome and sepsis].

OBJECTIVE: To evaluate the open and closed management treatment of liver injury in rats with sepsis and abdominal compartment syndrome (ACS). METHODS: The sepsis and ACS rats (n = 72) were randomized divided into two groups. One group used closed management (n = 36), the other accepted the open abdomen management (n = 36). The rats were killed at 1, 6 h, 1, 3, 5, 7 d after operation. Blood was collected for liver function tests. Liver sections assessed pathologically and the expressions of Toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, interleukin (IL)-6, signal transducers actuators of transcription (STAT3) and suppressor of cytokine signaling 3 (SOCS3) of rat livers were examined by RT-PCR. RESULTS: The early stage after operation, TNF-α and IL-6 concentrations, STAT3 expressions in rat liver were higher in open abdomen rats than the closed management ones (P < 0.05). TLR4 and SOCS3 expressions 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). CONCLUSIONS: The 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 TLR4 expressions.