Shanjun Tan

Peritoneal Air Exposure Elicits an Intestinal Inflammation Resulting in Postoperative Ileus

Background. The pathogenesis of postoperative ileus (POI) is complex. The present study was designed to investigate the effects of peritoneal air exposure on the POI intestinal inflammation and the underlying mechanism. Methods. Sprague-Dawley rats were randomized into five groups (6/group): the control group, the sham group, and three exposure groups with peritoneal air exposure for 1, 2, or 3 h. At 24 h after surgery, we analyzed the gastrointestinal transit, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10, the myeloperoxidase activity, and the levels of TNF-α, IL-1β, IL-6, and IL-10 in the ileum and colon. The oxidant and antioxidant levels in the ileum and colon were analyzed by measuring malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). Results. Peritoneal air exposure caused an air-exposure-time-dependent decrease in the gastrointestinal transit. The length of peritoneal air exposure is correlated with the severity of both systemic and intestinal inflammations and the increases in the levels of MDA, SOD, GSH-Px, and T-AOC. Conclusions. The length of peritoneal air exposure is proportional to the degree of intestinal paralysis and the severity of intestinal inflammation, which is linked to the oxidative stress response.

Ginsenoside Rb1 improves energy metabolism in the skeletal muscle of an animal model of postoperative fatigue syndrome

BACKGROUND Postoperative fatigue syndrome (POFS) is a common clinical complication followed by almost every major abdominal surgery. Ginsenoside Rb1 (GRb1), a principle ginsenoside in ginseng, could exert a potent anti-fatigue effect on POFS. However, the mechanism is still unknown. Previous studies revealed that alterations in the energy metabolism in the skeletal muscle may play a vital role in the development and progression of fatigue. In the present study, we investigate the effect of GRb1 on energy metabolism in the skeletal muscle of a rat model of POFS induced by major small intestinal resection. METHODS GRb1 (10 mg/kg) was intraperitoneally administrated once daily for 1, 3, 7, and 10 d from the operation day, respectively. The locomotor activity was recorded every day, and total food intake was calculated starting from 24 h after surgery. After GRb1 treatment was completed, blood and skeletal muscle were sampled. The level of blood glucose was determined by an automatic biochemical analyzer. The content of adenosine triphosphate (ATP) in skeletal muscle was determined by high-performance liquid chromatography. The activity of energy metabolic enzymes Na(+)-K(+)-ATPase, pyruvate kinase, and succinate dehydrogenase (SDH) was assessed by commercially available kits. RESULTS The results revealed that GRb1 could increase locomotor activity of POFS rats and significantly increase their total food intake postoperatively (P < 0.05). Furthermore, GRb1 also significantly increased ATP content in the skeletal muscle of POFS rats (P < 0.05). Meanwhile, the activity of Na(+)-K(+)-ATPase and SDH in the skeletal muscle of POFS rats was enhanced by GRb1 (P < 0.05). However, no significant differences in blood glucose and pyruvate kinase were found between the POFS and GRb1 treatment rats (P > 0.05). CONCLUSIONS These results suggest that GRb1 may improve skeletal muscle energy metabolism in POFS, and the underlying mechanism may be associated with an increase in the content of ATP and an enhancement in the activity of energy metabolic enzymes such as Na(+)-K(+)-ATPase ATPase and SDH in the skeletal muscle.

Chemical sympathectomy attenuates inflammation, glycocalyx shedding and coagulation disorders in rats with acute traumatic coagulopathy.

Acute traumatic coagulopathy (ATC) may trigger sympathoadrenal activation associated with endothelial damage and coagulation disturbances. Overexcitation of sympathetic nerve in this state would disrupt sympathetic–vagal balance, leading to autonomic nervous system dysfunction. The aim of this study was to evaluate the autonomic function in ATC and its influence on inflammation, endothelial and coagulation activation. Male Sprague–Dawley rats were randomly assigned to sham, ATC control (ATCC) and ATC with sympathectomy by 6-hydroxydopamine (ATCS) group. Sham animals underwent the same procedure without trauma and bleeding. Following trauma and hemorrhage, rats underwent heart rate variability (HRV) test, which predicts autonomic dysfunction through the analysis of variation in individual R-R intervals. Then, rats were euthanized at baseline, and at 0, 1 and 2 h after shock and blood gas, conventional coagulation test and markers of inflammation, coagulation, fibrinolysis, endothelial damage and catecholamine were measured. HRV showed an attenuation of total power and high frequency, along with a rise of low frequency and low frequency : high frequency ratio in the ATC rats, which both were reversed by sympathectomy in the ATCS group. Additionally, sympathetic denervation significantly suppressed the increase of proinflammatory cytokines, tumor necrosis factor-&agr; and the fibrinolysis markers including tissue-type plasminogen activator and plasmin–antiplasmin complex. Serum catecholamine, soluble thrombomodulin and syndecan-1 were also effectively inhibited by sympathectomy. These data indicated that autonomic dysfunction in ATC involves both sympathetic activation and parasympathetic inhibition. Moreover, sympathectomy yielded anti-inflammatory, antifibrinolysis and endothelial protective effects in rats with ATC. The role of autonomic neuropathy in ATC should be explored further.

Berberine ameliorates intestinal mucosal barrier damage induced by peritoneal air exposure.

Berberine, an isoquinoline alkaloid derived from many medicinal plants, has been extensively used to treat various gastrointestinal diseases. In the present study, we investigated whether berberine could ameliorate intestinal mucosal barrier damage induced by peritoneal air exposure for 3 h. Peritoneal air-exposure rats received 100, 150, and 200 mg/kg berberine orally via gavage four times before and after surgery. Blood and terminal ileum samples were collected 24 h after surgery. The serum D-lactate levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Intestinal permeability was determined by measuring the intestinal clearance of fluorescein isothiocyanate (FITC)-dextran (FD4). Intestinal inflammation was assessed by measuring myeloperoxidase activity. Intestinal histopathology was also assessed. The results revealed that berberine decreased the serum D-lactate level, intestinal FD4 clearance, and myeloperoxidase activity. Edema and inflammation were reduced by berberine in the intestinal mucosa and submucosa, and the Chius scores, indices of intestinal mucosal injury, also decreased in the berberine-treated group. In addition, berberine exerted these protective effects in a dose-dependent manner, with a significant difference from the control group at doses of 150 and 200 mg/kg. The results suggest that berberine could ameliorate intestinal mucosal barrier damage induced by peritoneal air exposure, which is linked to its anti-inflammatory activity. Berberine may be a promising treatment for intestinal mucosal barrier damage in open abdominal surgery.

Insulin ameliorating endotoxaemia-induced muscle wasting is associated with the alteration of hypothalamic neuropeptides and inflammation in rats

Septic patients always develop muscle wasting, which delays the rehabilitation and contributes to the increased complications and mortality. Previous studies have implied the crucial role of central inflammation and neuropeptides in the energy balance and muscle metabolism. Insulin has been confirmed to attenuate muscle degradation and inhibit inflammation. We tested the hypothesis whether insulin ameliorating muscle wasting was associated with modulating hypothalamic inflammation and neuropeptides.

The Effect of Peritoneal Air Exposure on Intestinal Mucosal Barrier

Background. Damage of the intestinal mucosa barrier may result in intestinal bacterial and endotoxin translocation, leading to local and systemic inflammation. The present study was designed to investigate whether peritoneal air exposure induces damage of intestinal mucosal barrier. Methods. Sprague-Dawley rats (weighing 210 to 230 g) were randomized into five groups (6/group): a control group, a sham group, and three exposure groups with peritoneal air exposure for 1, 2, and 3 h, respectively. At 24 h after surgery, blood and terminal ileum were sampled. The serum D-lactate levels were determined using an ELISA kit. The intestinal permeability was determined by measuring the intestinal clearance of FITC-dextran (FD4). The histopathological changes in terminal ileum were also assessed. Results. Compared with the controls, peritoneal air exposure caused an increase in both serum D-lactate level and intestinal FD4 clearance, which were proportional to the length of peritoneal air exposure and correlated to Chius scores, indices for intestinal mucosal injury. Edema and inflammatory cells were also observed in mucosa and submucosa of ileum in three exposure groups. Conclusions. Peritoneal air exposure could induce damage to the intestinal mucosal barrier, which is proportional to the time length of peritoneal air exposure.

Endotoxemia-induced muscle wasting is associated with the change of hypothalamic neuropeptides in rats

In critical patients, sepsis-induced muscle wasting is considered to be an important contributor to complications and mortality. Previous work mainly focuses on the peripheral molecular mechanism of muscle degradation, however little evidence exists for the role of central nervous system in the process. In the present study, we, for the first time, characterized the relationship between muscle wasting and central neuropeptide changes in a septic model. Thirty-six adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) or saline. Twelve, 24 and 48 hrs after injection, skeletal muscle and hypothalamus tissues were harvested. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle ring finger 1 (MuRF-1) and muscle atrophy F-box (MAFbx), as well as 3-methyl-histidine (3-MH) and tyrosine release. Hypothalamic neuropeptides and inflammatory marker expressions were also measured in three time points. LPS injection caused an increase expression of MuRF-1 and MAFbx, and a significant higher release of 3-MH and tyrosine. Hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), agouti-related protein (AgRP) and neuropeptide Y (NPY) presented a dynamic change after LPS injection. Also, hypothalamic inflammatory markers, interleukin-1 β (IL-1β) and tumor necrosis factor α (TNF-α) increased substantially after LPS administration. Importantly, the expressions of POMC, AgRP and CART were well correlated with muscle atrophy gene, MuRF-1 expression. These findings suggest hypothalamic peptides and inflammation may participate in the sepsis-induced muscle wasting, but the exact mechanism needs further study.

Evaluation of Transversus Abdominis Plane (TAP) Block in Hernia Surgery: A Meta-analysis.

Background: Transversus abdominis plane (TAP) block reduces opiate requirements and pain scores in abdominal surgery, but the effect has not been evaluated in hernia surgery. The aim of this study was to evaluate the efficacy of TAP block in hernia surgery. Methods: A meta-analysis of randomized clinical trials (RCTs) evaluating the effect of TAP block in adults undergoing hernia surgery was performed. The primary outcomes were morphine requirements 24 hours after surgery and the number of rescue analgesia patients. Secondary outcomes were pain scores on rest and on movement at 24 hours after surgery, postoperative nausea and vomiting and general postoperative complications. Results: The search strategy yielded 231 articles after duplicates have been removed, and finally 8 RCTs with a total of 791 patients were included. In patients who received a TAP block, the cumulative morphine utilization was significantly reduced at 24 hours (weighted mean difference [WMD] −11.40 mg, −22.41 to −0.39; P=0.04). The number of patients needing a rescue analgesia (relative risk: 0.35, 0.22 to 0.55; P<0.001), the pain scores on rest 24 hours after surgery (WMD: −0.29, −0.55 to −0.04; P=0.02) and the pain scores on movement or coughing 24 hours after surgery (WMD: −0.70, −1.33 to −0.06; P=0.03) were all lower in patients who received a TAP block. There was also significant reduction in the postoperative nausea and vomiting, and the general postoperative complications in TAP block group. Conclusions: Within a heterogeneous group of RCTs, TAP block reduces postoperative morphine requirements and the severity of pain after hernia surgery.

Impact of β-adrenoceptor blockade on systemic inflammation and coagulation disturbances in rats with acute traumatic coagulopathy.

Background Sympathetic hyperactivity occurs early in acute traumatic coagulopathy (ATC) and is closely related to its development. β-adrenoceptor antagonists are known to alleviate adverse sympathetic effects and improve outcome in various diseases. We investigated whether β-blockers have protective effects against inflammation and endothelial and hemostatic disorders in ATC. Material/Methods ATC was induced in male Sprague-Dawley rats by trauma and hemorrhagic shock. Rats were randomly assigned to the sham, ATCC (ATC control), and ATCB (ATC with beta-adrenoceptor blockade) groups. Rats were injected intraperitoneally with propranolol or vehicle at baseline. Heart rate variability (HRV) and markers of inflammation, coagulation, and endothelial activation were measured, and Western blotting analysis of nuclear factor (NF)-κB was done after shock. Separate ATCC and ATCB groups were observed to compare overall mortality. Results HRV showed enhanced sympathetic tone in the ATCC group, which was reversed by propranolol. Propranolol attenuated the induction of pro-inflammatory cytokines TNF-α and IL-6, as well as fibrinolysis markers plasmin antiplasmin complex and tissue-type plasminogen activator. The increased serum syndecan-1 and soluble thrombomodulin were inhibited by propranolol, and the NF-κB expression was also decreased by propranolol pretreatment. But propranolol did not alter overall mortality in rats with ATC after shock. Conclusions Beta-adrenoceptor blockade can alleviate sympathetic hyperactivity and exert anti-inflammatory, anti-fibrinolysis, and endothelial protective effects, confirming its pivotal role in the pathogenesis of ATC. Its mechanism in ATC should be explored further.

A time course study of acute traumatic coagulopathy prior to resuscitation: From hypercoagulation to hypocoagulation caused by hypoperfusion?

INTRODUCTION Coagulopathy after sever injury predicts the requirements of blood products, organ failure and mortality in traumatic patients. The early onset and complexity of traumatic coagulopathy preclude the understanding the underlying mechanism. The aim of the study is to characterize the early coagulation alteration in a swine model with multi-trauma and shock. METHODS Twelve pigs were subjected to multi-trauma (femur fracture, laparotomy, 10 cm intestine resection and grade III injury of liver) and hemorrhaged to a mean arterial pressure (MAP) of 40 mmHg. Physiologic parameters and coagulation variables (prothrombin time (PT), international normalized ratio (INR), fibrinogen, antithrombin-III (AT-III) activity, D-dimer and thromboelastography (TEG)) were measured after instrumentation (baseline), 5 min after multi-trauma (after trauma), 10 min (early shock) and 40 min (late shock) after hemorrhage. A group of 6 instrumented pigs were used as control. RESULTS Multi-trauma and hemorrhage caused significant increase of base excess (BE) and lactate (p<0.05). PT shortened after multi-trauma but increased significantly at late shock (p<0.05). Fibrinogen reduced greatly after trauma and at early shock (p<0.05), while remained stable afterwards. AT-III activity decreased throughout the experiment. Reaction time (R) shortened after trauma and at early shock (both p<0.05). Maximal amplitude (MA) decreased significantly during the shock period. CONCLUSION After traumatic hemorrhagic shock, hypercoagulation turned into hypocoagulation in a short period, which was probably caused by hypoperfusion.