The economic burden of gastroschisis: costs of a birth defect.

BACKGROUND: Intestinal dysfunction and feeding intolerance are comorbidities associated with the abdominal wall birth defect of gastroschisis (GS). These factors contribute to prolonged hospitalization in this population of patients. The purpose of this study was to evaluate the economic burden on a state and national level. METHODS: From 2007-2011, the Healthcare Cost and Utilization Project database was queried for the following national and state of Texas data: number of discharges, length of stay (LOS), costs, and charges for all pediatric hospital stays ± CPT code 54.71 denoting GS repair for infants aged <1 y. The effect of GS on LOS, cost, and charges was calculated by the weighted average of the differences and is represented by the combined estimated difference (CED). RESULTS: Infants <1 y represent 74% of all pediatric discharges nationally and only 0.04% of these discharges are accounted for by GS patients. Nationally, GS patients had significantly longer LOS (CED 38.5 ± 0.9 d, P < 0.0001); increased costs (CED $79,733 ± $2119, P < 0.0001); and charges (CED $249,999 ± $9562, P < 0.0001). The Texas state data mirrored our findings for the national data. There was no significant difference in the LOS, costs, and charges between the national and state level. CONCLUSIONS: Our study shows that GS patients represent an extremely small minority of national and Texas pediatric discharges; however, these patients LOS and costs greatly exceed non-GS patients. Further investigation into factors influencing the development of intestinal dysfunction in these patients is needed to significantly impact the economic burden of the abdominal wall birth defect of GS.

Effects of nonocclusive mesenteric hypertension on intestinal function: implications for gastroschisis-related intestinal dysfunction.

INTRODUCTION: Infants with gastroschisis (GS) have significant morbidity from dysmotility, feeding intolerance, and are at increased risk of developing intestinal failure. Although the molecular mechanisms regulating GS-related intestinal dysfunction (GRID) are largely unknown, we hypothesized that mechanical constriction (nonocclusive mesenteric hypertension (NMH)) from the abdominal wall defect acts as a stimulus for GRID. The purpose of this study was to determine the effect of NMH on intestinal function and inflammation. METHODS: Neonatal rats had placement of a silastic disk to the base of the mesentery (NMH) or no disk placement (Sham). At 24 and 72 h, mesenteric venous pressures (MVPs), intestinal transit, electric impedance, permeability, length, and tissue water content were measured. RESULTS: After placement of the silastic disk, there was a significant increase in MVP at both time points. There was also decreased intestinal transit. As compared to Sham animals, NMH animals had significant changes in bowel impedance without an increase in tissue water, suggesting significant intestinal remodeling. NMH rats had significantly increased smooth-muscle thickness and loss of intestinal length as compared with Sham rats. DISCUSSION: NMH may be an initiating factor for GRID. Measurement of MVP and/or bowel impedance may be a way to assess severity and monitor progression and/or resolution of GRID.

Evaluating the potential role of nitric oxide as a mediator of hydrostatic edema mediated intestinal contractile dysfunction.

BACKGROUND: Administration of L-nil, a selective inhibitor of inducible nitric oxide synthase (iNOS), improves ileus in an animal model of resuscitation induced intestinal edema. The purpose of this study was to elucidate the iNOS/nitric oxide (NO) signal transduction pathway in intestinal edema. MATERIALS AND METHODS: Male Sprague Dawley rats were divided into two groups; CONTROL and RESUS+VH (edema, 80 cc/kg normal saline (resuscitation) with mesenteric venous hypertension). iNOS mRNA and protein, iNOS activity, NO tissue levels, soluble guanylyl cyclase (sGC) expression, and cyclic guanosine monophosphate (cGMP) levels were measured. As a functional endpoint, we evaluated intestinal contractile strength and frequency in L-nil treated animals. RESULTS: Edema was associated with increased iNOS mRNA and protein expression without subsequent increases in iNOS activity or tissue NO levels. There was no significant change in sGC expression or increase in cGMP induced by edema. Administration of L-nil did not decrease edema development or preserve contractile strength, but increased contractile frequency. CONCLUSION: Hydrostatic intestinal edema is not associated with increased iNOS activity or tissue NO levels. Administration of L-nil in edema increases intestinal contractile frequency. This may represent a potential mechanism for the amelioration of ileus seen with the administration of L-nil.

Intestinal ischemic preconditioning after ischemia/reperfusion injury in rat intestine: profiling global gene expression patterns.

OBJECTIVE: Intestinal ischemia/reperfusion (IR) injury involves activation of inflammatory mediators, mucosal necrosis, ileus, and alteration in a variety of gene products. Ischemic preconditioning (IPC) reduced all the effects of intestinal injury seen in IR. In an effort to investigate the molecular mechanisms responsible for the protective effects afforded by IPC, we sought to characterize the global gene expression pattern in rats subjected to IPC in the setting of IR injury. METHODS: Rats were randomized into five groups: (1) Sham, (2) IPC only (3) IR, (4) Early IPC + IR (IPC --> IR), and (5) Late IPC + IR (IPC --> 24 h --> IR). At 6 h after reperfusion, ileum was harvested for total RNA isolation, pooled, and analyzed on complementary DNA (cDNA) microarrays with validation using real-time polymerase chain reaction (PCR). Significance Analysis of Microarray (SAM) software was used to determine statistically significant changes in gene expression. RESULTS: Early IPC + IR had 5,167 induced and 4 repressed genes compared with the other groups. SAM analysis revealed 474 out of 10,000 genes differentially expressed among the groups. Early and Late IPC + IR had more genes involved in redox hemostasis, the immune/inflammatory response, and apoptosis than either the IPC only or IR alone groups. CONCLUSION: The transcriptional profile suggests that IPC exerts its protective effects by regulating the gene response to injury in the intestine.

Intestinal edema: effect of enteral feeding on motility and gene expression.

OBJECTIVE: Edema formation, inflammation, and ileus in the intestine are commonly seen in conditions like gastroschisis, inflammatory bowel disease, and cirrhosis. We hypothesized that early enteral feeding would improve intestinal transit. We also wanted to study the impact of early enteral feeding on global gene expression in the intestine. DESIGN: Rats were divided into Sham or Edema +/- immediate enteral nutrition (IEN). At 12 h, small intestinal transit via FITC-Dextran and tissue water were measured. Ileum was harvested for total RNA to analyze gene expression using cDNA microarray with validation using real-time PCR. Data are expressed as mean +/- SEM, n = 4-6 and (*), (**) = P < 0.05 versus all groups using ANOVA. RESULTS: IEN markedly improved intestinal transit with minimal genetic alterations in Edema animals. Major alterations in gene expression were detected in primary, cellular and macromolecular metabolic activities. Edema also altered more genes involved with the regulation of the actin cytoskeleton. CONCLUSIONS: Intestinal edema results in impaired small intestinal transit and globally increased gene expression. Early enteral nutrition improves edema-induced impaired transit and minimizes gene transcriptional activity.

Peroxisome proliferator-activated receptor gamma mediates protection against cyclooxygenase-2-induced gut dysfunction in a rodent model of mesenteric ischemia/reperfusion.

Cyclooxygenase (COX)-2 has been identified as an important mediator elaborated during ischemia/reperfusion, with pro- and anti-inflammatory properties having been reported. As the role of COX-2 in the small intestine remains unclear, we hypothesized that COX-2 expression would mediate mesenteric ischemia/reperfusion-induced gut injury, inflammation, and impaired transit and that these deleterious effects could be reversed by the selective COX-2 inhibitor, N-[2-(cyclohexyloxy)-4-nitrophenyl] methanesulphanamide (NS-398). Additionally, we sought to determine the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in mediating protection by NS-398 in this model. Rats underwent sham surgery or were pretreated with NS-398 (3, 10, or 30 mg/kg) intraperitoneally 1 h before 60 min of superior mesenteric artery occlusion and 30 min to 6 h of reperfusion. In some experiments, NS-398 (30 mg/kg) was administered postischemia. Ileum was harvested for COX-2 mRNA and protein, PGE2, myeloperoxidase (inflammation), histology (injury), intestinal transit and PPARgamma protein expression, and DNA-binding activity. COX-2 expression and PGE2 production increased after mesenteric ischemia/reperfusion and were associated with gut inflammation, injury, and impaired transit. Inhibition of COX-2 by NS-398 (30 mg/kg, but not 3 or 10 mg/kg) not only reversed the deleterious effects of COX-2, but additionally induced expression and nuclear translocation of PPARgamma. NS-398 given postischemia was equally protective. In conclusion, COX-2 may function as a proinflammatory mediator in a rodent model of mesenteric ischemia/reperfusion. Reversal of gut inflammation, injury, and impaired transit by high-dose NS-398 is associated with PPAR activation, suggesting a potential role for PPAR-gamma in shock-induced gut protection.

Ischemic preconditioning protects against gut dysfunction and mucosal injury after ischemia/reperfusion injury.

Mesenteric ischemia/reperfusion (IR) damages the gastrointestinal epithelia and impairs gut function. Ischemic preconditioning (IPC) has been shown to protect organs against IR injury. We hypothesized that IPC protects the gut from IR injury. Rats were randomized to a sham group, a sham early IPC + IR group (sham IPC + SMA occlusion for 30 min and 6 h of reperfusion), an early IPC + IR group (IPC, three cycles of SMA occlusion for 4 min and reperfusion for 10 min) followed immediately by SMA occlusion for 30 min and 6 h of reperfusion), a sham 24-h group, a sham late IPC + IR group (sham IPC followed by additional reperfusion for 24 h + SMA occlusion for 30 min and 6 h of reperfusion), and a late IPC + IR group (IPC protocol followed by additional reperfusion for 24 h, and then SMA occlusion for 30 min followed by 6 h of reperfusion). At 6 h, transit was determined and expressed as the mean geometric center. Ileum was harvested for assessment of mucosal injury and myeloperoxidase (MPO) activity. Tissue water was determined using the wet-to-dry weight ratio to assess gut edema. Early IPC + IR significantly improved transit (3.9 +/- 0.2), decreased MPO levels (3 +/- 2), and lessened mucosal injury (1.2 +/- 0.3) compared with animals subjected to sham early IPC + IR (transit, 2.9 +/- 0.2; MPO levels, 9 +/- 1; mucosal injury, 3.0 +/- 0.6). Late IPC + IR also improved transit (6.0 +/- 0.4) and decreased MPO levels (1 +/- 1) compared with sham late IPC + IR (transit, 4.4 +/- 0.2; MPO levels, 8 +/- 1), however, there was no difference in the mucosal protection between late IPC + IR (1 +/- 0.3) and sham late IPC + IR (1 +/- 1). Our results suggest that early and late IPC improves intestinal dysfunction, decreases inflammation, and provides mucosal protection in the intestine after IR. Our results show that IR-induced gut dysfunction can be improved by IPC. Both phases of IPC can potentially be useful in the clinical setting of surgical patient care.

Effects of primary and secondary intra-abdominal hypertension on mesenteric lymph flow: implications for the abdominal compartment syndrome.

Intra-abdominal hypertension leading to abdominal compartment syndrome complicates trauma resuscitation. The purpose of this study was to determine the effect of primary (1 degrees) and secondary (2 degrees) intra-abdominal hypertension (IAH) on hemodynamics, intestinal fluid balance, and mesenteric lymph flow. Anesthetized dogs were instrumented with vascular catheters, intra-abdominal manometer, and mesenteric lymphatic fistulae. 1 degrees IAH was created by infusing 0.9% saline into the peritoneal cavity to increase abdominal pressure. 2 degrees IAH was created by elevating the inferior vena cava (IVC) pressure between 20 and 25 mmHg and crystalloid resuscitation to create intestinal edema to induce IAH. At baseline and at 30-min intervals, hemodynamics, lymph flow (QL), IVC, and intra-abdominal pressures were measured. Tissue water was determined using microgravimetry to assess gut edema. Results are reported as mean +/- SEM, with n = 7-8 dogs per group. 1 degrees IAH significantly increased CVP and decreased QL. 1 degrees IAH stopped mesenteric QL, thus transvascular fluid flux necessarily exceeded QL, contributing to gut edema formation. 2 degrees IAH significantly increased CVP and QL. 2 degrees IAH increased QL despite elevated IAP. Interstitial protein washdown maintained the plasma-to-interstitial oncotic gradient, thus increased transvascular fluid flux was due principally to increased capillary pressure. Transvascular fluid flux exceeded QL as manifested by increasing gut tissue water as QL plateaued. Modest elevations in IAP significantly affect mesenteric QL and the development of gut edema. The principle of early abdominal decompression to reduce mesenteric/IVC venous hypertension and capillary pressure is supported by these data.

Improving gastroschisis outcomes: does birth place matter?

PURPOSE: Babies born in the hospital where they obtain definitive surgical care do not require transportation between institutions and may have shorter time to surgical intervention. Whether these differences result in meaningful improvement in outcomes has been debated. A multi-institutional retrospective study was performed comparing outcomes based on birthplace. METHODS: Six institutions within the PedSRC reviewed infants born with gastroschisis from 2008 to 2013. Birthplace, perinatal, and postoperative data were collected. Based on the P-NSQIP definition, inborn was defined as birth at the pediatric hospital where repair occurred. The primary outcome was days to full enteral nutrition (FEN; 120kcal/kg/day). RESULTS: 528 patients with gastroschisis were identified: 286 inborn, 242 outborn. Days to FEN, time to bowel coverage and abdominal wall closure, primary closure rate, and length of stay significantly favored inborn patients. In multivariable analysis, birthplace was not a significant predictor of time to FEN. Gestational age, presence of atresia or necrosis, primary closure rate, and time to abdominal wall closure were significant predictors. CONCLUSIONS: Inborn patients had bowel coverage and definitive closure sooner with fewer days to full feeds and shorter length of stay. Birthplace appears to be important and should be considered in efforts to improve outcomes in patients with gastroschisis.

Strategies for modulating the inflammatory response after decompression from abdominal compartment syndrome.

BACKGROUND: Management of the open abdomen is an increasingly common part of surgical practice. The purpose of this review is to examine the scientific background for the use of temporary abdominal closure (TAC) in the open abdomen as a way to modulate the local and systemic inflammatory response, with an emphasis on decompression after abdominal compartment syndrome (ACS). METHODS: A review of the relevant English language literature was conducted. Priority was placed on articles published within the last 5 years. RESULTS/CONCLUSION: Recent data from our group and others have begun to lay the foundation for the concept of TAC as a method to modulate the local and/or systemic inflammatory response in patients with an open abdomen resulting from ACS.

An evidence-based review of a Lentinula edodes mushroom extract as complementary therapy in the surgical oncology patient.

The purpose of this review is to present the currently published evidence regarding the use, efficacy, potential mechanisms of action, and results of published clinical trials regarding the use of a Lentinula edodes mushroom-derived extract (active hexose correlated compound) as complementary therapy in patients with cancer. The authors explore the current preclinical and clinical evidence as it relates to this topic and its potential use in the surgical oncology patient. There has been a growing interest in stimulation of the immune system in trauma, cancer, and surgical patients in general. Little, however, has been written about some-of the supplements in widely used in Japan and China, but relatively unheard of in the United States.

Hydrostatic intestinal edema induced signaling pathways: potential role of mechanical forces.

BACKGROUND: Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema. METHODS: The distal intestine from adult male Sprague Dawley rats was stretched longitudinally for 2 h to 123% its original length, which correlates with the interstitial stress found with edema. We compared wet-to-dry ratios, myeloperoxidase activity, nuclear signal transduction and activator of transcription (STAT)-3 and nuclear factor (NF)-kappa B DNA binding, STAT-3 phosphorylation, myosin light chain phosphorylation, baseline and maximally stimulated intestinal contractile strength, and inducible nitric oxide synthase (iNOS) and sodium hydrogen exchanger 1-3 messenger RNA (mRNA) in stretched and adjacent control segments of intestine. RESULTS: Mechanical stretch did not induce intestinal edema or an increase in myeloperoxidase activity. Nuclear STAT-3 DNA binding, STAT-3 phosphorylation, and nuclear NF-kappa B DNA binding were significantly increased in stretched seromuscular samples. Increased expression of sodium hydrogen exchanger 1 was found but not an increase in iNOS expression. Myosin light chain phosphorylation was significantly decreased in stretched intestine as was baseline and maximally stimulated intestinal contractile strength. CONCLUSION: Intestinal stretch, in the absence of edema/inflammatory/ischemic changes, leads to the activation of signaling pathways known to be altered in intestinal edema. Edema may initiate a mechanotransductive cascade that is responsible for the subsequent activation of various signaling cascades known to induce contractile dysfunction.

Pretreatment with bone morphogenetic protein-7 (BMP-7) mimics ischemia preconditioning following intestinal ischemia/reperfusion injury in the intestine and liver.

Intestinal ischemia/reperfusion (I/R) injury has been shown to cause intestinal mucosal injury and adversely affect function. Ischemic preconditioning (IPC) has been shown to protect against intestinal I/R injury by reducing polymorphonuclear leukocyte infiltration, intestinal mucosal injury, and liver injury, and preserve intestinal transit. Bone morphogenetic protein 7 (BMP-7) has been shown to protect against I/R injury in the kidney and brain. Recently, microarray analysis has been used to examine the possible IPC candidate pathways. This work revealed that IPC may work through upregulation of BMP-7. The purpose of this study was to examine if pretreatment with BMP-7 would replicate the effects seen with IPC in the intestine and liver after intestinal I/R. Rats were randomized to six groups: sham, I/R (30 min of superior mesenteric artery occlusion and 6 h of R), IPC+R (three cycles of superior mesenteric artery occlusion for 4 min and R for 10 min), IPC+I/R, BMP-7+R (100 microm/kg recombinant human BMP-7), or BMP-7+I/R. A duodenal catheter was placed, and 30 min before sacrifice, fluorescein isothiocyanate-Dextran was injected. At sacrifice, dye concentrations were measured to determine intestinal transit. Ileal mucosal injury was determined by histology and myeloperoxidase activity was used as a marker of polymorphonuclear leukocyte infiltration. Serum levels of aspartate aminotransferase were measured at sacrifice to determine liver injury. Pretreatment with BMP-7 significantly improved intestinal transit and significantly decreased intestinal mucosal injury and serum aspartate aminotransferase levels, comparable to animals undergoing IPC. In conclusion, BMP-7 protected against intestinal I/R-induced intestinal and liver injury. Bone morphogenetic protein 7 may be a more logical surrogate to IPC in the prevention of injury in the setting of intestinal I/R.

Hypertonic saline reverses stiffness in a Sprague-Dawley rat model of acute intestinal edema, leading to improved intestinal function.

INTRODUCTION: Acute edema induced by resuscitation and mesenteric venous hypertension impairs intestinal transit and contractility and reduces intestinal stiffness. Pretreatment with hypertonic saline (HS) can prevent these changes. Changes in tissue stiffness have been shown to trigger signaling cascades via stress fiber formation. We proposed that acute intestinal edema leads to a decrease in intestinal transit that may be mediated by changes in stiffness, leading to stress fiber formation and decreased intestinal transit. Furthermore, HS administration will abolish these detrimental effects of edema. RESULTS: Intestinal edema causes a significant increase in tissue water and a significant decrease in intestinal transit and stiffness compared with sham. HS reversed these changes to sham levels. In addition, tissue edema led to significant stress fiber formation and decreased numbers of focal contacts. HS preserved tissue stiffness, prevented stress fiber formation, and was associated with improved intestinal function. CONCLUSION: HS eliminates intestinal tissue edema formation and improves intestinal transit. In addition, the action of HS may be mediated through its preservation of tissue stiffness, which leads to prevention of signaling via stress fiber formation, leading to preserved intestinal function. Finally, intestinal edema may provide a novel physiologic model for examining stiffness and stress fiber signaling.

Measurement of intestinal edema using an impedance analyzer circuit.

BACKGROUND: Acute intestinal edema adversely affects intestinal transit, permeability, and contractility. Current resuscitation modalities, while effective, are associated with development of acute intestinal edema. Knowledge of levels of tissue edema would allow clinicians to monitor intestinal tissue water and may help prevent the detrimental effects of edema. However, there is no simple method to measure intestinal tissue water without biopsy. We sought to develop a tissue impedance analyzer to measure tissue edema, without the need for invasive biopsy. METHODS: Oscillating voltage input was applied to the analyzer circuit and an oscilloscope measured the voltage output across any load. Rats were randomized to three groups: sham, mild edema (80 mL/kg of NS resuscitation), and severe edema (80 mL/kg of NS resuscitation with intestinal venous hypertension). Intestinal edema was measured by wet-to-dry tissue weight ratio. Bowel impedance was measured and converted to capacitance using a standard curve. RESULTS: Acute intestinal edema causes a significant increase in bowel capacitance. This capacitance can be used to predict tissue water concentration. CONCLUSION: Using an impedance analyzer circuit, it is possible to measure intestinal edema reliably and quickly. This may prove to be a useful tool in the resuscitation of critically ill patients.

Hypertonic saline resuscitation prevents hydrostatically induced intestinal edema and ileus.

OBJECTIVE: We have shown that acute edema induced by mesenteric venous hypertension (MV-HTN) impairs intestinal transit and reduces the standardized engineering measures of intestinal stiffness (elastic modulus) and residual stress (opening angle). We hypothesized that hypertonic saline (7.5%) would reverse these detrimental effects of acute edema. DESIGN: Laboratory study. SETTING: University laboratory. SUBJECTS: Male Sprague Dawley rats (270-330 g). INTERVENTIONS: Rats were randomized to five groups: sham, MV-HTN alone, MV-HTN with 4 mL/kg normal saline resuscitation (equal volume), MV-HTN with 33 mL/kg normal saline resuscitation (equal salt), and MV-HTN with 4 mL/kg hypertonic saline. Intestinal edema was measured by wet to dry tissue weight ratio. A duodenal catheter was placed and, 30 mins before death, fluorescein isothiocyanate Dextran was injected. At death, dye concentrations were measured to determine intestinal transit. Segments of distal ileum were hung to a fixed point in a tissue bath and to a force displacement transducer and stretched in increments of 1 mm; we recorded the new length and the corresponding force from the force displacement transducer to determine elastic modulus. Next, two transverse cuts were made yielding a 1- to 2-mm thick ring-shaped segment of tissue which was then cut radially to open the ring. Then the opening angle was measured. MEASUREMENTS AND MAIN RESULTS: MV-HTN, MV-HTN with 4 mL/kg normal saline, and MV-HTN with 33 mL/kg normal saline caused a significant increase in tissue edema and a significant decrease in intestinal transit, stiffness, and residual stress compared with sham. Hypertonic saline significantly lessened the effect of edema on intestinal transit and prevented the changes in stiffness and residual stress. CONCLUSIONS: Hypertonic saline prevented intestinal tissue edema. In addition, hypertonic saline improved intestinal transit, possibly through more efficient transmission of muscle force through stiffer intestinal tissue.

Ketamine inhibits lipopolysacharide (LPS) induced gastric luminal fluid accumulation.

INTRODUCTION: Lipopolysacharide (LPS) causes gastrointestinal ileus and gastric luminal fluid accumulation. Ketamine, an anti-inflammatory anesthetic agent attenuates accumulation of luminal fluid. However, its effects on gastrointestinal transit induced by endotoxemia are unknown. The purpose of this study was to determine if the anti-inflammatory properties of ketamine improve impaired gastric emptying and gastrointestinal transit because of LPS. MATERIALS AND METHODS: Rats were given ketamine (70 mg/kg i.p.) or saline 1 h before LPS (20 mg/kg, i.p.) or saline injection. Five hours after LPS injection, rats were gavaged with 1 cc consisting of 0.1 ml of 5 mm FITC Dextran added to 0.9 ml of saline. After 30 min, rats were sacrificed, and gastric emptying, gastrointestinal transit, and gastric fluid accumulation determined. Gastric and ileal mucosa were harvested for analysis of inducible nitric oxide synthase (iNOS) (Western immunoblot). Results are reported as mean +/- SE (n > or = 5 per group; ANOVA). RESULTS: Ketamine did not prevent LPS induced gastrointestinal ileus, nor did it improve gastric emptying. More importantly, it did not worsen gastrointestinal function or gastric emptying when compared to saline controls. However, it did decrease LPS induced gastric luminal fluid accumulation and blunted iNOS expression in both the stomach and ileum. CONCLUSION: These data indicate that the ability of ketamine to attenuate gastric fluid accumulation is not because of improved gastric emptying or improved gastrointestinal transit. Moreover, while iNOS may play a role in LPS induced gastric luminal fluid accumulation, it does not appear to be a major mediator of the gastrointestinal ileus caused by LPS.

Resuscitation-induced gut edema and intestinal dysfunction.

BACKGROUND: Mesenteric venous hypertension and subsequent gut edema play a pivotal role in the development of intra-abdominal hypertension. Although gut edema is one cause of intra-abdominal hypertension, its impact on gut function is unknown. The purpose of this study was to create a model of acute hydrostatic gut edema and to evaluate its effect on gut motility and barrier function. METHODS: The first study, group A, evaluated the effect of gut edema on transit over time using 20 mL/kg 0.9% saline. The second study, group B, focused on the 12-hour time period using 80 mL/kg 0.9% saline. Rats were randomized to superior mesenteric vein partial occlusion (venous hypertension) or sham surgery. At 6, 12, and 24 hours, group A underwent intestinal transit and tissue water weight measurements. At 12 hours, group B underwent tissue water, transit, ileal permeability and resistance, lactate and myeloperoxidase activity, and mucosal injury measurements. RESULTS: Venous hypertension with fluid resuscitation caused acute hydrostatic gut edema, delayed intestinal transit, increased mucosal permeability to macromolecules, and decreased tissue resistance over time. Mucosal injury was minimal in mesenteric venous hypertension. CONCLUSION: Acute mesenteric venous hypertension and resuscitation-induced gut edema, in the absence of ischemia/reperfusion injury, is associated with delayed intestinal transit and altered gut barrier function.