Splanchnic oxygenation during phototherapy in preterm infants with hyperbilirubinemia.

BACKGROUND: It has been reported that preterm infants can develop feeding intolerance during phototherapy (PT) and that PT can affect mesenteric perfusion in these patients. AIMS: Our aim was to assess if PT can decrease regional splanchnic oxygenation (rSO2S) measured by near infrared spectroscopy (NIRS). STUDY DESIGN: We prospectively studied infants with gestational age of 25-34 weeks with hyperbilirubinemia requiring PT. Splanchnic regional oxygenation (rSO2S), oxygen extraction fraction (FOES), and cerebrosplanchnic oxygenation ratio (CSOR) were recorded before, during, and after PT discontinuation. RESULTS: During PT rSO2S and CSOR significantly decreased and this effect lasted for some hours after its interruption. FOES contemporary increased, although this effect was not statistically significant. CONCLUSIONS: PT treatment decreases splanchnic oxygenation in preterm infants likely due to peripheral vasodilation which triggers a redistribution of blood flow. These results can help explain the association between PT and the development of feeding intolerance in preterm infants.

Yogic agnisara increases blood flow in the superior mesenteric artery.

OBJECTIVES: Medieval yoga texts claim that a special exercise of the muscles of the anterior abdominal wall, called agnisara, improves digestive function. Main objective of the study was to demonstrate change in the blood flow through superior mesenteric artery (if any) after performance of agnisara. METHODS: Ultrasound examination of the linear and volumetric indicators of blood flow in the superior mesenteric artery (SMA) before and after performing the agnisara yoga exercise 100 times was carried out in 12 healthy volunteers of both sexes (8 of them women). RESULTS: A significant increase in the diameter of the SMA, peak systolic and diastolic velocities, and blood flow in the superior mesenteric artery after performing the agnisara exercise 100 times was found, which contrasts with the established data on a decrease in splanchnic blood flow in humans in response to normal physical activity. CONCLUSION: Properly performed agnisara increases blood flow to the splanchnic region, registered by the SMA, which should contribute to adequate blood supply to the gastrointestinal tract for successful performance of digestive function.

Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study.

Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non-SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36.

Potential for Gut Peptide-Based Therapy in Postprandial Hypotension.

Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.

Moringa oleifera leaf extract enhances endothelial nitric oxide production leading to relaxation of resistance artery and lowering of arterial blood pressure.

A mass of evidence has identified a promoting of nitric oxide (NO) production in endothelial cells using natural products as a potential strategy to prevent and treat hypertension. This study investigated whether the aqueous extract of Moringa oleifera leaves (MOE) could lower mean arterial pressure (MAP) and relax mesenteric arterial beds in rats via stimulating endothelium-derived NO production. Intravenous administration of MOE (1-30 mg/kg) caused a dose-dependent reduction in MAP in anesthetized rats. In rats pretreated with the NO-synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg, i.v.), the effect of MOE on MAP was significantly reduced. MOE (0.001-3 mg) induced relaxation in methoxamine (10 µM) pre-contracted mesenteric arterial beds, which was abolished by endothelium denudation. This endothelium-dependent vasorelaxation was reduced by L-NAME (100 µM) or the NO-sensitive guanylyl cyclase inhibitor, 1H- [1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (10 µM). In primary human pulmonary artery endothelial cells, MOE (3-30 µg/mL) induced NO production, which was inhibited by L-NAME (100 µM) pretreatment. These findings show that MOE stimulates the endothelium-derived NO release for driving its vasorelaxation to lower arterial blood pressure. These suggest the development of MOE as a natural antihypertensive supplement.

Increasing Blood Pressure by Greater Splanchnic Nerve Stimulation: a Feasibility Study.

The splanchnic vascular compartment is the major reservoir for intravascular blood volume, and dysregulation of the compartment was implicated in a series of cardiovascular conditions. We explored feasibility and effectiveness of an implantable cuff system on the greater splanchnic nerve (GSN) in healthy canines for short- and long-term neuromodulation to affect the circulation. Five mongrel hounds underwent minimally invasive right-sided unilateral GSN cuff placement. All animals underwent same day GSN stimulation and repeat stimulation at 9-30 days. Stimulation parameter optimization was conducted both acutely and chronically. Parameters ranged from 1-250 Hz, 0.25 mA-35 mA, 0.1-0.5 ms, and 30-s pulse duration. Two animals were survived for 9 days and 3 animals for 30 days. Stimulation of the right GSN increased mean arterial blood pressure by 36.9 mmHg ± 13.4 (p < 0.0001), central venous pressure by 6.9 mmHg ± 1.7 (p < 0.0001), and mean pulmonary arterial pressure by 6.3 mmHg ± 2.0 (p < 0.0001). Peak effects were observed within 30 s, and magnitude of effects was comparable between stimulation cycles (p = 0.4). Stimulation-induced changes in hemodynamics were independent of afferent nerve fibers (pain response) or the adrenal gland. Necropsy showed no evidence of nerve damage on histologic studies up to 30 days after implantation. GSN stimulation via an implanted nerve cuff provided a reproducible and rapid method to increase arterial, central venous, and pulmonary arterial pressures. The neuromodulation cuff was well tolerated and elicited a response up to 30 days after implantation. The clinical application of GSN stimulation as a tool to change central and peripheral cardiovascular hemodynamics needs to be explored.

Osteopathic Manipulation Treatment Improves Cerebro-splanchnic Oximetry in Late Preterm Infants.

Background: To evaluate the effectiveness/side-effects of osteopathic manipulation treatment (OMT) performed on the 7th post-natal day, on cerebro-splanchnic oximetry, tissue activation and hemodynamic redistribution in late preterm (LP) infants by using near infrared spectroscopy (NIRS). Methods: Observational pretest-test study consisting in a cohort of 18 LPs who received OMT on the 7th post-natal day. NIRS monitoring was performed at three different time-points: 30 min before (T0), (30 min during (T1) and 30 min after OMT (T2). We evaluated the effects of OMT on the following NIRS parameters: cerebral (c), splanchnic (s) regional oximetry (rSO2), cerebro-splanchnic fractional tissue oxygen extraction (FTOE) and hemodynamic redistribution (CSOR). Results: crSO2 and cFTOE significantly (P < 0.001) improved at T0-T2; srSO2 significantly (P < 0.001) decreased and sFTOE increased at T0-T1. Furthermore, srSO2 and sFTOE significantly improved at T1-T2. Finally, CSOR significantly (P < 0.05) increased at T0-T2. Conclusions: The present data show that OMT enhances cerebro-splanchnic oximetry, tissue activation and hemodynamic redistribution in the absence of any adverse clinical or laboratory pattern. The results indicate the usefulness of further randomized studies in wider populations comparing the effectiveness of OMT with standard rehabilitation programs.

Folic acid ameliorates homocysteine-induced angiogenesis and portosystemic collaterals in cirrhotic rats.

INTRODUCTION AND OBJECTIVES: Liver cirrhosis is characterized by increased intrahepatic resistance, splanchnic vasodilation/angiogenesis, and formation of portosystemic collateral vessels. Collaterals can cause lethal complications such as gastroesophageal variceal hemorrhage. Homocysteine is linked to vascular dysfunction and angiogenesis and higher levels have been reported in cirrhotic patients. It is also known that folic acid supplementation reverses the effects of homocysteine. However, the treatment effect in cirrhosis has yet to be investigated. MATERIAL AND METHODS: Liver cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (CBDL). The CBDL rats randomly received (1) vehicle; (2) dl-homocysteine thiolactone (1g/kg/day); (3) dl-homocysteine thiolactone plus folic acid (100mg/kg/day); or (4) folic acid. On the 29th day, hemodynamic parameters, liver and renal biochemistry, protein expressions of proangiogenic factors, mesenteric vascular density and portosystemic shunting were evaluated. RESULTS: In the cirrhotic rats, homocysteine increased mesenteric vascular density and the severity of shunting. It also up-regulated the protein expressions of mesenteric vascular endothelial growth factor (VEGF) and phosphorylated-endothelial nitric oxide synthase (p-eNOS). These effects were reversed by folic acid treatment (P<0.05). CONCLUSION: Folic acid ameliorated the adverse effects of homocysteine in the cirrhotic rats, which may be related to down-regulation of the VEGF-NO signaling pathway.

Sucrose but Not Nitrate Ingestion Reduces Strenuous Cycling-induced Intestinal Injury.

PURPOSE: Strenuous exercise induces intestinal injury, which is likely related to splanchnic hypoperfusion and may be associated with gastrointestinal complaints commonly reported during certain exercise modalities. Increasing circulating nitric oxide (NO) levels or inducing postprandial hyperemia may improve splanchnic perfusion, thereby attenuating intestinal injury during exercise. Therefore, we investigated the effects of both dietary nitrate ingestion and sucrose ingestion on splanchnic perfusion and intestinal injury induced by prolonged strenuous cycling. METHODS: In a randomized crossover manner, 16 well-trained male athletes (age, 28 ± 7 yr; Wmax, 5.0 ± 0.3 W·kg) cycled 60 min at 70% Wmax after acute ingestion of sodium nitrate (NIT; 800 mg NO3), sucrose (SUC; 40 g), or a water placebo (PLA). Splanchnic perfusion was assessed by determining the gap between gastric and arterial pCO2 (gapg-apCO2) using gastric air tonometry. Plasma intestinal fatty acid-binding protein (I-FABP) concentrations, reflecting enterocyte damage, were assessed every 20 min during and up to 60 min of postexercise recovery. RESULTS: The exercise protocol resulted in splanchnic hypoperfusion, as gapg-apCO2 levels increased during exercise (P < 0.001), with no differences between treatments (P = 0.47). Although plasma I-FABP concentrations increased during exercise and postexercise recovery for all treatments (P < 0.0001), the increase was different between treatments (P < 0.0001). Post hoc comparisons showed an attenuated increase in I-FABP in SUC versus PLA (P = 0.020). In accordance, I-FABP area under the curve (AUC0-120) was significantly lower in SUC versus PLA (57,270 ± 77,425 vs 114,907 ± 91,527 pg·mL per 120 min, P = 0.002). No differences were observed between NIT and PLA (P = 0.99). CONCLUSION: Sucrose but not nitrate ingestion lowers intestinal injury evoked during prolonged strenuous cycling. These results suggest that sucrose ingestion, but not nitrate, prevents hypoperfusion-induced gastrointestinal damage during exercise and, as such, may help to lower exercise-related gastrointestinal complaints.

Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success.

BACKGROUND: Renal denervation has no validated marker of procedural success. We hypothesized that successful renal denervation would reduce renal sympathetic nerve signaling demonstrated by attenuation of α-1-adrenoceptor-mediated autotransfusion during the Valsalva maneuver. METHODS AND RESULTS: In this substudy of the Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension, we enrolled 23 subjects with resistant hypertension. They were randomized either to bilateral renal denervation using therapeutic levels of ultrasound energy (n=12) or sham application of diagnostic ultrasound (n=11). Within-group changes in autonomic parameters, office and ambulatory blood pressure were compared between baseline and 6 months in a double-blind manner. There was significant office blood pressure reduction in both treatment (16.1±27.3 mm Hg, P<0.05) and sham groups (27.9±15.0 mm Hg, P<0.01) because of which the study was discontinued prematurely. However, during the late phase II (Iii) of Valsalva maneuver, renal denervation resulted in substantial and significant reduction in mean arterial pressure (21.8±25.2 mm Hg, P<0.05) with no significant changes in the sham group. Moreover, there were significant reductions in heart rate in the actively treated group at rest (6.0±11.5 beats per minute, P<0.05) and during postural changes (supine 7.2±8.4 beats per minute, P<0.05, sit up 12.7±16.7 beats per minute, P<0.05), which were not observed in the sham group. CONCLUSIONS: Blood pressure reduction per se is not necessarily a marker of successful renal nerve ablation. Reduction in splanchnic autotransfusion following renal denervation has not been previously demonstrated and denotes attenuation of (renal) sympathetic efferent activity and could serve as a marker of procedural success. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02029885.

Autodigestion by migrated trypsin is a major factor in small intestinal ischemia-reperfusion injury.

BACKGROUND: The pathophysiological role of pancreatic digestive hydrolases in intestinal ischemia-reperfusion (I/R) injury is still not clear. Here, we studied whether ischemia-induced injury to the small intestine can be explained by the autodigestion hypothesis. MATERIALS AND METHODS: Mesenteric I/R was induced in rats by superior mesenteric artery occlusion (90 min) and reopening (120 min). Thirty minutes before superior mesenteric artery occlusion, aprotinin (14.7 mg/kg), orlistat (5 mg/kg), and their combination or α1-proteinase inhibitor (60 mg/kg) were injected into the lumen of the small intestine. Systemic and vital parameters, intestinal microcirculation, and mucosal barrier function were monitored during the observation phase; markers of small intestinal injury, as well as trypsin-, chymotrypsin-, elastase-, and lipase-like activities in intestinal effluates were assessed at the end. RESULTS: The pattern of small intestinal injury correlated inversely with the local alterations in microvascular tissue perfusion and corresponded with the intestinal distribution of trypsin-like activity. Aprotinin almost completely inhibited trypsin-like activity (P < 0.05) and significantly reduced intestinal tissue injury. Combined with orlistat, it also increased the postischemic blood pressure (P < 0.05) but not the intestinal barrier function. Macroscopic as well as the histologic alterations were decreased by α1-proteinase inhibitor, which significantly improved postischemic blood pressure (P < 0.05). CONCLUSIONS: The I/R-induced pattern of small intestinal injury is likely to result from both local differences in tissue ischemia and the digestive activity of migrated pancreatic trypsin. Therefore, administration of aprotinin and orlistat into ischemic small intestines may be a therapeutic option in patients with a poor diagnosis.

Inhibition of epoxyeicosatrienoic acid production in rats with cirrhosis has beneficial effects on portal hypertension by reducing splanchnic vasodilation.

UNLABELLED: In cirrhosis, 11,12-epoxyeicosatrienoic acid (EET) induces mesenteric arterial vasodilation, which contributes to the onset of portal hypertension. We evaluated the hemodynamic effects of in vivo inhibition of EET production in experimental cirrhosis. Sixteen control rats and 16 rats with carbon tetrachloride-induced cirrhosis were studied. Eight controls and eight rats with cirrhosis were treated with the specific epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH; 20 mg/kg/day) for 3 consecutive days. Portal blood flow and renal and splenic resistive indexes were calculated through echographic measurements, while portal and systemic pressures were measured through polyethylene-50 catheters. Small resistance mesenteric arteries were connected to a pressure servo controller in a video-monitored perfusion system, and concentration-response curves to phenylephrine and acetylcholine were evaluated. EET levels were measured in tissue homogenates of rat liver, kidney, and aorta, using an enzyme-linked immunosorbent assay. Urinary Na(+) excretion function was also evaluated. In rats with cirrhosis, treatment with MS-PPOH significantly reduced portal blood flow and portal pressure compared to vehicle (13.6 ± 5.7 versus 25.3 ± 7.1 mL/min/100 g body weight, P < 0.05; 9.6 ± 1.1 versus 12.2 ± 2.3 mm Hg, P < 0.05; respectively) without effects on systemic pressure. An increased response to acetylcholine of mesenteric arteries from rats with cirrhosis (50% effect concentration -7.083 ± 0.197 versus -6.517 ± 0.73 in control rats, P < 0.05) was reversed after inhibition of EET production (-6.388 ± 0.263, P < 0.05). In liver, kidney, and aorta from animals with cirrhosis, treatment with MS-PPOH reversed the increase in EET levels. In both controls and rats with cirrhosis, MS-PPOH increased urinary Na(+) excretion. CONCLUSION: In rats with cirrhosis, in vivo inhibition of EET production normalizes the response of mesenteric arteries to vasodilators, with beneficial effects on portal hypertension. (Hepatology 2016;64:923-930).

Contribution of Cyclooxygenase End Products and Oxidative Stress to Intrahepatic Endothelial Dysfunction in Early Non-Alcoholic Fatty Liver Disease.

INTRODUCTION: Metabolic syndrome induces endothelial dysfunction, a surrogate marker of cardiovascular disease. In parallel, metabolic syndrome is frequently associated with non-alcoholic fatty liver disease (NAFLD), which may progress to cirrhosis. The aim of the present study was to evaluate intrahepatic endothelial dysfunction related to cyclooxygenase end products and oxidative stress as possible mechanisms involved in the pathophysiology of NAFLD. MATERIALS AND METHODS: Sprague-Dawley rats were fed standard diet (control-diet, CD) or high-fat-diet (HFD) for 6 weeks. Metabolic syndrome was assessed by recording arterial pressure, lipids, glycemia and rat body weight. Splanchnic hemodynamics were measured, and endothelial dysfunction was evaluated using concentration-effect curves to acetylcholine. Response was assessed with either vehicle, L-NG-Nitroarginine (L-NNA), indomethacin, tempol, or a thromboxane receptor antagonist, SQ 29548. We quantified inflammation, fibrosis, oxidative stress, nitric oxide (NO) bioavailability and thromboxane B2 levels. RESULTS: HFD rats exhibited metabolic syndrome together with the presence of NAFLD. Compared to control-diet livers, HFD livers showed increased hepatic vascular resistance unrelated to inflammation or fibrosis, but with decreased NO activity and increased oxidative stress. Endothelial dysfunction was observed in HFD livers compared with CD rats and improved after cyclooxygenase inhibition or tempol pre-incubation. However, pre-incubation with SQ 29548 did not modify acetylcholine response. CONCLUSIONS: Our study provides evidence that endothelial dysfunction at an early stage of NAFLD is associated with reduced NO bioavailability together with increased cyclooxygenase end products and oxidative stress, which suggests that both pathways are involved in the pathophysiology and may be worth exploring as therapeutic targets to prevent progression of the disease.

Whole-body and splanchnic amino acid metabolism in sheep during an acute endotoxin challenge.

Supplemented protein or specific amino acids (AA) are proposed to help animals combat infection and inflammation. The current study investigates whole-body and splanchnic tissue metabolism in response to a lipopolysaccharide (LPS) challenge with or without a supplement of six AA (cysteine, glutamine, methionine, proline, serine and threonine). Eight sheep were surgically prepared with vascular catheters across the gut and liver. On two occasions, four sheep were infused through the jugular vein for 20 h with either saline or LPS from Escherichia coli (2 ng/kg body weight per min) in a random order, plus saline infused into the mesenteric vein; the other four sheep were treated with saline or LPS plus saline or six AA infused via the jugular vein into the mesenteric vein. Whole-body AA irreversible loss rate (ILR) and tissue protein metabolism were monitored by infusion of [ring-2H2]phenylalanine. LPS increased (P<0·001) ILR (+17 %), total plasma protein synthesis (+14 %) and lymphocyte protein synthesis (+386 %) but decreased albumin synthesis (-53 %, P=0·001), with no effect of AA infusion. Absorption of dietary AA was not reduced by LPS, except for glutamine. LPS increased the hepatic removal of leucine, lysine, glutamine and proline. Absolute hepatic extraction of supplemented AA increased, but, except for glutamine, this was less than the amount infused. This increased net appearance across the splanchnic bed restored arterial concentrations of five AA to, or above, values for the saline-infused period. Infusion of key AA does not appear to alter the acute period of endotoxaemic response, but it may have benefits for the chronic or recovery phases.

Management of Acute Mesenteric Ischemia: A Critical Review and Treatment Algorithm.

BACKGROUND: Acute mesenteric ischemia (AMI) due to a sudden loss or decrease in blood perfusion to the mesentery represents a highly lethal condition. However, the optimal surgical management remains debatable and merits a more clear recommendation based on a higher level of evidence. METHODS: A systematic review of articles published between 2000 and 2013 was performed. Patients were divided into endovascular treatment (ET), open surgery (OS), and hybrid technique (HT) groups. Data of patients' demographics, procedural information, clinical outcomes including mortality, morbidity, primary patency rate, technique success, primary intestinal resection rate, and second-look laparotomy rate, and follow-up were all retrieved. Comparison between the ET and the OS groups was made using 2-sided Student t test and 2-sided χ(2) test or Fisher exact test where appropriate. RESULTS: Twenty-eight articles with a total of 1110 patients were included for the review. The ET group had lower in-hospital mortality and morbidity but similar survival rate during follow-up compared to the OS group. The primary patency rate was higher in the ET group. The overall bowel resection rate was lower in the ET group, and nearly every patient in the cohort who required second-look laparotomy required bowel resection. The HT group seemed to have the lowest mortality and acceptable second-look laparotomy rate and morbidity. Comparison between the HT group and other groups was not possible due to the limited number of cases available for review. CONCLUSION: Endovascular treatment may serve as a first-line therapy for select patients when there is a low suspicion for intestinal necrosis. Open surgery should be reserved for emergency conditions requiring exploratory laparotomy. Hybrid technique may be an especially effective approach for treating AMI, with low morbidity and mortality, although further studies are required comparing it to OS and ET.

Effects of Proanthocyanidins on Intestinal Motility Disturbance Following Intestinal Ischemia/Reperfusion.

PURPOSE: To investigate the potential protective effects of Proanthocyanidins(PAs) on intestinal motility disturbance following intestinal ischemia/reperfusion (I/R). MATERIALS AND METHODS: Male rats were divided into four groups: Sham, I/R, I/R+PA100 and I/R+PA200. Sham group underwent laparotomy without ligation, the others were subjected to intestinal ischemia for 1 h and reperfusion 4 h. Rats in the I/R+PA100 group received PAs (100 mg/kg/d) for 5 days prior to I/R, while rats in the I/R+PA200 group received PAs (200 mg/kg/d). After reperfusion, using an electrophysiology instrument measured ileal slow wave. Ileal specimens were obtained to determine contractility, tissue levels of Bax, Bcl-2, and Caspase-3 and evaluate histopathological changes. In addition, blood sample was obtained to determine serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels. RESULTS: Intestinal I/R caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, and hemorrhage. Both PAs treatment decreased mucosal pathological impairment in comparison with the I/R group (p < .05) in light microscopic evaluations. In both PAs-treated groups, Bax and Caspase-3 expression were decreased compared to I/R group, while the Bcl-2 expression increased (p < .05), which was similarly the case for serum SOD activity demonstrated significant enhance (p < .05) and decline in MDA levels in comparison with I/R group (both p < .05). Moreover, PAs treatment was more efficient in attenuating serum MDA levels of intestinal I/R (both p < .05). And the contractile amplitude and frequency of slow wave in I/R+PA100 and I/R+PA200 groups were higher than I/R group (both p < .05). CONCLUSIONS: PAs improve intestinal motility disturbance following intestinal I/R by alleviating oxidative stress and apoptosis.

Does hyperbaric oxygen therapy reduce the effects of ischemia on colonic anastomosis in laparoscopic colon resection?

BACKGROUND: An increase in intra-abdominal pressure causes a decrease in the splanchnic blood flow and the intramucosal pH of the bowel, as well as increasing the risk of ischemia in the colon. The aim of the present study is to evaluate the effect of hyperbaric oxygen therapy (HBOT) on the ischemia caused by laparoscopy in colonic anastomosis in an experimental model of laparoscopic colonic surgery. MATERIALS AND METHODS: We divided 30 male Wistar albino rats into three groups: Group A was the control (open colon anastomosis); Group B received LCA (laparoscopic colon anastomosis); while Group C received both LCA and HBOT. Each group contained ten animals. We placed Group C (LCA and HBOT) in an experimental hyperbaric chamber into which we administered pure oxygen at 2.1 atmospheres absolute 100% oxygen for 60 min for ten consecutive days. RESULTS: The anastomotic bursting pressure value was found to be higher in the open surgery group (226 ± 8.8) (Group A). The result for Group C (213 ± 27), which received HBOT, was better than that for Group B (197 ± 27). However, there was no statistically significant difference between Group B and Group C. Group A showed better healing than the other groups, while significant differences in the fibroblast proliferation scores were found between Groups A and B. In terms of tissue hydroxyproline levels, a significant difference was found between Groups A and B and between Groups A and C, but not between Groups B and C. CONCLUSIONS: HBOT increases the oxygen level in the injured tissue. Although HBOT might offer several advantages, it had only a limited effect on the healing of colonic anastomosis in rats with increased intra-abdominal pressure in our study. KEY WORDS: Anastomosis, Colon, Hyperbaric Oxygen Treatment, Oxidative Stress.

Glytan decreases portal pressure via mesentery vasoconstriction in portal hypertensive rats.

AIM: To investigate the effects of Glytan on splanchnic hemodynamics and its reduction of portal pressure in portal hypertensive rats. METHODS: Glytan (Ganluotong in Chinese), is composed of salvianolic acid B and diammonium glycyrrhizinate. Portal hypertension (PHT) was induced in the rats by common bile duct ligation (BDL). Hemodynamic studies were performed using the colored microsphere method. Radioimmunoassay (RIA) was used to determine endothelin (ET)-1 levels in the mesenteric circulation. Western blotting methods were used to investigate the effect of Glytan on ET A receptor (ETAR), ET B receptor (ETBR), endothelial NO synthase (eNOS), G-protein-coupled receptor kinase (GRK)2, and ß-arrestin 2 expression in the mesentery. The mRNA of ETAR and ETBR was determined using real-time polymerase chain reaction. RESULTS: Treatment with Glytan reduced portal pressure (PP) and portal territory blood flow (PTBF) and increased both mean arterial pressure (MAP) and splanchnic vascular resistance (SVR). Especially at 4 wk, PP decreased by about 40%, while MAP increased by 13%, SVR increased by 12%, and PTBF decreased by about 21%. The effect of blood flow reduction was greatest in the mesentery (about 33%) at 4 wk. The mesenteric circulation ET-1 levels of BDL rats were lower and negatively correlated with PP at 4 wk. Glytan can increase mesenteric ET-1 content and inhibit ETBR, eNOS, GRK2, and ß-arrestin 2 expression in the mesentery. Moreover, Glytan showed no effect on the expression of ETAR protein and mRNA. CONCLUSION: The decreased PP and PTBF observed after Glytan treatment were related to increased mesenteric vasoconstriction and increased receptor sensitivity to vasoconstrictor.

Isolating and using sections of bovine mesenteric artery and vein as a bioassay to test for vasoactivity in the small intestine.

Mammalian gastrointestinal systems are constantly exposed to compounds (desirable and undesirable) that can have an effect on blood flow to and from that system. Changes in blood flow to the small intestine can result in effects on the absorptive functions of the organ. Particular interest in toxins liberated from feedstuffs through fermentative and digestive processes has developed in ruminants as an area where productive efficiencies could be improved. The video associated with this article describes an in vitro bioassay developed to screen compounds for vasoactivity in isolated cross-sections of bovine mesenteric artery and vein using a multimyograph. Once the blood vessels are mounted and equilibrated in the myograph, the bioassay itself can be used: as a screening tool to evaluate the contractile response or vasoactivity of compounds of interest; determine the presence of receptor types by pharmacologically targeting receptors with specific agonists; determine the role of a receptor with the presence of one or more antagonists; or determine potential interactions of compounds of interest with antagonists. Through all of this, data are collected real-time, tissue collected from a single animal can be exposed to a large number of different experimental treatments (an in vitro advantage), and represents vasculature on either side of the capillary bed to provide an accurate picture of what could be happening in the afferent and efferent blood supply supporting the small intestine.

L-citrulline improves splanchnic perfusion and reduces gut injury during exercise.

PURPOSE: Splanchnic hypoperfusion is a physiological phenomenon during strenuous exercise. It has been associated with gastrointestinal symptoms and intestinal injury and may hamper athletic performance. We hypothesized that L-citrulline supplementation improves splanchnic perfusion and decreases intestinal injury by enhancing arginine availability. The aim of this study was to determine the effect of L-citrulline intake on splanchnic perfusion, intestinal injury, and barrier function during exercise. METHODS: In this randomized, double-blind crossover study, 10 men cycled for 60 min at 70% of their maximum workload after L-citrulline (10 g) or placebo (L-alanine) intake. Splanchnic perfusion was assessed using gastric air tonometry. Sublingual microcirculation was evaluated by sidestream dark field imaging. Plasma amino acid levels and intestinal fatty acid binding protein concentrations, reflecting enterocyte damage, were assessed every 10 min. Urinary excretion of sugar probes was measured to evaluate intestinal permeability changes. RESULTS: Oral L-citrulline supplementation enhanced plasma citrulline (1840.3 ± 142.3 µM) and arginine levels (238.5 ± 9.1 µM) compared with that in placebo (45.7 ± 4.8 µM and 101.5 ± 6.1 µM, respectively, P < 0.0001), resulting in increased arginine availability. Splanchnic hypoperfusion was prevented during exercise after L-citrulline ingestion (reflected by unaltered gapg-apCO2 levels), whereas gapg-apCO2 increased with placebo treatment (P < 0.01). Accordingly, L-citrulline intake resulted in an increased number of perfused small sublingual vessels compared with that in placebo (7.8 ± 6.0 vs -2.0 ± 2.4, P = 0.06). Furthermore, plasma intestinal fatty acid binding protein levels were attenuated during exercise after L-citrulline supplementation compared with that in placebo (AUC0-60 min, -185% ± 506% vs 1318% ± 553%, P < 0.01). No significant differences were observed for intestinal permeability. CONCLUSIONS: Pre-exercise L-citrulline intake preserves splanchnic perfusion and attenuates intestinal injury during exercise in athletes compared with placebo, probably by enhancing arginine availability. These results suggest that oral L-citrulline supplementation is a promising intervention to combat splanchnic hypoperfusion-induced intestinal compromise.