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Walter R. Hasibeder - One of the best experts on this subject based on the ideXlab platform.
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Arginine-vasopressin attenuates beneficial norepinephrine effect on jejunal Mucosal Tissue oxygenation during endotoxinaemia
British journal of anaesthesia, 2009Co-Authors: S. Maier, Walter R. Hasibeder, Werner Pajk, Hanno Ulmer, Hans Hausdorfer, C. Hengl, Bettina Wurzinger, Hans KnotzerAbstract:Background The objective of the present study was to investigate the effects of increasing doses of norepinephrine (NE) with or without arginine-vasopressin (AVP) on intestinal oxygen supply and jejunal Mucosal Tissue oxygen tension in an acute endotoxic pig model. Methods In this prospective, randomized, experimental study on 24 domestic pigs, jejunal Mucosal Tissue P o 2 (P o 2muc) was measured using two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular haemoglobin (HbO2j) was determined by Tissue reflectance spectrophotometry. Systemic haemodynamic variables, mesenteric-venous and systemic acid–base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli lipopolysaccharide (LPS) administration, and at 20 min intervals during incremental NE infusion (0.05, 0.1, 0.5, 1.0, and 2 µg kg−1 min−1, respectively) with 57 mU kg−1 h−1 AVP (n=8; NE+AVP group) or without (n=8; NE group); or infusion of an equal amount of normal saline (n=8; CON group). Results LPS infusion led to a significant (P o 2muc and HbO2j. Both NE and NE+AVP increased arterial pressure, cardiac output, and mesenteric artery blood flow. Concomitant to an increase in systemic oxygen delivery, NE improved P o 2muc and HbO2j. NE alone was superior in restoration of P o 2muc when compared with NE+AVP. Conclusions Both NE and NE+AVP improved global haemodynamics and systemic oxygen transport variables when compared with control animals in an acute endotoxic pig model. NE improved jejunal P o 2muc at all dosages. NE effects were significantly blunted by simultaneous administration of AVP.
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Epoprostenol improves Mucosal Tissue oxygen tension in an acute endotoxemic pig model.
Shock (Augusta Ga.), 2009Co-Authors: S. Maier, Walter R. Hasibeder, Werner Pajk, Hanno Ulmer, Hans Hausdorfer, Christian Torgersen, Josef Klocker, Hans KnotzerAbstract:ABSTRACT The objective of the present study was to determine the effects of increasing dosages of continuously infused epoprostenol (PGI), a prostacyclin analog, on intestinal oxygen supply and jejunal Mucosal Tissue oxygen tension in an acute endotoxic pig model. Jejunal Mucosal Tissue PO2, oxygen saturation of jejunal microvascular hemoglobin, and gut microvascular blood flow were investigated. Systemic hemodynamic variables, mesenteric-venous and systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli LPS administration, and at 20-min intervals during incremental PGI infusion (n = 8; 25, 50, 100, and 200μg·kg−1·h−1, respectively); or infusion of an equal amount of isotonic sodium chloride solution (n = 7). LPS infusion led to a significant decrease in Mucosal Tissue oxygen tension and microvascular hemoglobin oxygen saturation. Epoprostenol infusion led to a significant, dose-dependent increase in cardiac index and systemic oxygen delivery. Mucosal Tissue oxygen tension and microvascular hemoglobin oxygen saturation increased after PGI administration and even returned to more-than-baseline values. Continuously infused PGI increased intestinal hemoglobin oxygen saturation and Mucosal Tissue oxygen tension in a dose-dependent manner mainly due to an increase in villus blood flow in this acute endotoxic pig model.
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Arginine vasopressin does not alter Mucosal Tissue oxygen tension and oxygen supply in an acute endotoxemic pig model
Intensive care medicine, 2005Co-Authors: Hans Knotzer, Walter R. Hasibeder, Barbara Friesenecker, S. Maier, Hanno Ulmer, Hans Hausdorfer, Christian Torgersen, Martin W. Dünser, Julia Brandner, Claudia IannettiAbstract:Objective To determine the effects of increasing dosages of continuously infused arginine-vasopressin (AVP) on Mucosal Tissue oxygen tension and oxygen supply in an auto-perfused, innervated jejunal segment in an acute endotoxic porcine model.
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Arginine vasopressin reduces intestinal oxygen supply and Mucosal Tissue oxygen tension.
American journal of physiology. Heart and circulatory physiology, 2005Co-Authors: Hans Knotzer, Werner Pajk, Hanno Ulmer, Stephan E. Maier, Ruth Ladurner, Axel Kleinsasser, Volker Wenzel, Martin W. Dünser, Walter R. HasibederAbstract:We investigated intestinal oxygen supply and Mucosal Tissue Po2 during administration of increasing dosages of continuously infused arginine vasopressin (AVP) in an autoperfused, innervated jejunal...
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Dopamine and intestinal Mucosal Tissue oxygenation in a porcine model of haemorrhage.
British journal of anaesthesia, 1997Co-Authors: R. Germann, M. Haisjackl, Birgit Schwarz, Werner Pajk, Engelbert Deusch, Natalie Salak, H. J. Wolf, B. Riedmann, Walter R. HasibederAbstract:Haemorrhage is associated with intestinal Mucosal hypoxia and impaired gut barrier function. Dopamine increases oxygen delivery to the intestinal mucosa and may thus counteract haemorrhage-induced Mucosal hypoxia. Jejunal Mucosal Tissue oxygen tension (Mucosal PO2) and jejunal oxygen saturation of Mucosal microvascular haemoglobin (Mucosal HbO2) were measured in 14 anaesthetized pigs. Seven animals served as controls (group C) and seven received continuous infusion of dopamine 16 micrograms kg-1 min-1 (group D) while 45% of blood volume was removed in three equal increments. Resuscitation was performed using shed blood and fluid. Mean arterial pressure and systemic oxygen delivery decreasing significantly during haemorrhage and returned to baseline after resuscitation in both groups. Mucosal PO2 decreased from 4.4 to 1.7 kPa after haemorrhage (P
Charlene S. Dezzutti - One of the best experts on this subject based on the ideXlab platform.
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Broadly neutralizing anti-HIV antibodies prevent HIV infection of Mucosal Tissue ex vivo
Antimicrobial agents and chemotherapy, 2015Co-Authors: Yanille Scott, Seo Young Park, Charlene S. DezzuttiAbstract:Broadly neutralizing monoclonal antibodies (nAbs) specific for HIV are being investigated for use in HIV prevention. Due to their ability to inhibit HIV attachment to and entry into target cells, nAbs may be suitable for use as topical HIV microbicides. As such, they would present an alternative intervention for individuals who may not benefit from using antiretroviral-based products for HIV prevention. We theorize that nAbs can inhibit viral transmission through Mucosal Tissue, thus reducing the incidence of HIV infection. The efficacy of the PG9, PG16, VRC01, and 4E10 antibodies was evaluated in an ex vivo human model of Mucosal HIV transmission. nAbs reduced HIV transmission, causing 1.5- to 2-log10 reductions in HIV replication in ectocervical Tissues and ≈3-log10 reductions in HIV replication in colonic Tissues over 21 days. These antibodies demonstrated greater potency in colonic Tissues, with a 50-fold higher dose being required to reduce transmission in ectocervical Tissues. Importantly, nAbs retained their potency and reduced viral transmission in the presence of whole semen. No changes in Tissue viability or immune activation were observed in colonic or ectocervical Tissue after nAb exposure. Our data suggest that topically applied nAbs are safe and effective against HIV infection of Mucosal Tissue and support further development of nAbs as a topical microbicide that could be used for anal as well as vaginal protection.
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Animal and human Mucosal Tissue models to study HIV biomedical interventions: can we predict success?
Journal of the International AIDS Society, 2015Co-Authors: Charlene S. DezzuttiAbstract:Introduction: Preclinical testing plays an integral role in the development of HIV prevention modalities. Several models are used including humanized mice, non-human primates and human Mucosal Tissue cultures. Discussion : Pharmaceutical development traditionally uses preclinical models to evaluate product safety. The HIV prevention field has extended this paradigm to include models of efficacy, encompassing humanized mice, non-human primates (typically Asian macaques) and human Mucosal Tissue (such as cervical and colorectal). As our understanding of the biology of HIV transmission improves and includes the influence of human behaviour/biology and co-pathogens, these models have evolved as well to address more complex questions. These three models have demonstrated the effectiveness of systemic (oral) and topical use of antiretroviral drugs. Importantly, pharmacokinetic/pharmacodynamic relationships are being developed and linked to information gathered from human clinical trials. The models are incorporating co-pathogens (bacterial and viral) and the effects of coitus (Mucosal fluids) on drug distribution and efficacy. Humanized mice are being tailored in their immune reconstitution to better represent humans. Importantly, human Mucosal Tissue cultures are now being used in early clinical trials to provide information on product efficacy to more accurately characterize efficacious products to advance to larger clinical trials. While all of these models have made advancements in product development, each has limitations and the data need to be interpreted by keeping these limitations in mind. Conclusions : Development and refinement of each of these models has been an iterative process and linkages to data generated among each of them and from human clinical trials are needed to determine their reliability. Preclinical testing has evolved from simply identifying products that demonstrate efficacy prior to clinical trials to defining essential pharmacokinetic/pharmacodynamic relationships under a variety of conditions and has the potential to improve product selection prior to the initiation of large-scale human clinical trials. The goal is to provide researchers with ample information to make conversant decisions that guide optimized and efficient product development. Keywords: HIV prevention; pre-exposure prophylaxis; microbicide; humanized mouse; non-human primate; macaque; Mucosal Tissue; ex vivo challenge. (Published: 2 November 2015) Citation: Dezzutti CS. Journal of the International AIDS Society 2015, 18 :20301 http://www.jiasociety.org/index.php/jias/article/view/20301 | http://dx.doi.org/10.7448/IAS.18.1.20301
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Use of Human Mucosal Tissue to Study HIV-1 Pathogenesis and Evaluate HIV-1 Prevention Modalities
Current HIV AIDS Reports, 2013Co-Authors: Charlene S. Dezzutti, Florian HladikAbstract:The use of human Mucosal Tissue models is an important tool advancing our understanding of the specific mechanisms of sexual HIV transmission. Despite 30 years of study, major gaps remain, including how HIV-1 transverses the epithelium and the identity of the early immune targets (gate keepers). Because defining HIV-1 transmission in vivo is difficult, Mucosal Tissue is being used ex vivo to identify key steps in HIV-1 entry and early dissemination. Elucidating early events of HIV-1 infection will help us develop more potent and specific HIV-1 preventatives such as microbicides and vaccines. Mucosal Tissue has been incorporated into testing regimens for antiretroviral drugs and monoclonal antibodies. The use of Mucosal Tissue recapitulates the epithelium and immune cells that would be exposed in vivo to virus and drug. This review will discuss the use of Mucosal Tissue to better understand HIV-1 pathogenesis and prevention modalities.
Hans Knotzer - One of the best experts on this subject based on the ideXlab platform.
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Arginine-vasopressin attenuates beneficial norepinephrine effect on jejunal Mucosal Tissue oxygenation during endotoxinaemia
British journal of anaesthesia, 2009Co-Authors: S. Maier, Walter R. Hasibeder, Werner Pajk, Hanno Ulmer, Hans Hausdorfer, C. Hengl, Bettina Wurzinger, Hans KnotzerAbstract:Background The objective of the present study was to investigate the effects of increasing doses of norepinephrine (NE) with or without arginine-vasopressin (AVP) on intestinal oxygen supply and jejunal Mucosal Tissue oxygen tension in an acute endotoxic pig model. Methods In this prospective, randomized, experimental study on 24 domestic pigs, jejunal Mucosal Tissue P o 2 (P o 2muc) was measured using two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular haemoglobin (HbO2j) was determined by Tissue reflectance spectrophotometry. Systemic haemodynamic variables, mesenteric-venous and systemic acid–base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli lipopolysaccharide (LPS) administration, and at 20 min intervals during incremental NE infusion (0.05, 0.1, 0.5, 1.0, and 2 µg kg−1 min−1, respectively) with 57 mU kg−1 h−1 AVP (n=8; NE+AVP group) or without (n=8; NE group); or infusion of an equal amount of normal saline (n=8; CON group). Results LPS infusion led to a significant (P o 2muc and HbO2j. Both NE and NE+AVP increased arterial pressure, cardiac output, and mesenteric artery blood flow. Concomitant to an increase in systemic oxygen delivery, NE improved P o 2muc and HbO2j. NE alone was superior in restoration of P o 2muc when compared with NE+AVP. Conclusions Both NE and NE+AVP improved global haemodynamics and systemic oxygen transport variables when compared with control animals in an acute endotoxic pig model. NE improved jejunal P o 2muc at all dosages. NE effects were significantly blunted by simultaneous administration of AVP.
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Epoprostenol improves Mucosal Tissue oxygen tension in an acute endotoxemic pig model.
Shock (Augusta Ga.), 2009Co-Authors: S. Maier, Walter R. Hasibeder, Werner Pajk, Hanno Ulmer, Hans Hausdorfer, Christian Torgersen, Josef Klocker, Hans KnotzerAbstract:ABSTRACT The objective of the present study was to determine the effects of increasing dosages of continuously infused epoprostenol (PGI), a prostacyclin analog, on intestinal oxygen supply and jejunal Mucosal Tissue oxygen tension in an acute endotoxic pig model. Jejunal Mucosal Tissue PO2, oxygen saturation of jejunal microvascular hemoglobin, and gut microvascular blood flow were investigated. Systemic hemodynamic variables, mesenteric-venous and systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli LPS administration, and at 20-min intervals during incremental PGI infusion (n = 8; 25, 50, 100, and 200μg·kg−1·h−1, respectively); or infusion of an equal amount of isotonic sodium chloride solution (n = 7). LPS infusion led to a significant decrease in Mucosal Tissue oxygen tension and microvascular hemoglobin oxygen saturation. Epoprostenol infusion led to a significant, dose-dependent increase in cardiac index and systemic oxygen delivery. Mucosal Tissue oxygen tension and microvascular hemoglobin oxygen saturation increased after PGI administration and even returned to more-than-baseline values. Continuously infused PGI increased intestinal hemoglobin oxygen saturation and Mucosal Tissue oxygen tension in a dose-dependent manner mainly due to an increase in villus blood flow in this acute endotoxic pig model.
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Arginine vasopressin does not alter Mucosal Tissue oxygen tension and oxygen supply in an acute endotoxemic pig model
Intensive care medicine, 2005Co-Authors: Hans Knotzer, Walter R. Hasibeder, Barbara Friesenecker, S. Maier, Hanno Ulmer, Hans Hausdorfer, Christian Torgersen, Martin W. Dünser, Julia Brandner, Claudia IannettiAbstract:Objective To determine the effects of increasing dosages of continuously infused arginine-vasopressin (AVP) on Mucosal Tissue oxygen tension and oxygen supply in an auto-perfused, innervated jejunal segment in an acute endotoxic porcine model.
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Arginine vasopressin reduces intestinal oxygen supply and Mucosal Tissue oxygen tension.
American journal of physiology. Heart and circulatory physiology, 2005Co-Authors: Hans Knotzer, Werner Pajk, Hanno Ulmer, Stephan E. Maier, Ruth Ladurner, Axel Kleinsasser, Volker Wenzel, Martin W. Dünser, Walter R. HasibederAbstract:We investigated intestinal oxygen supply and Mucosal Tissue Po2 during administration of increasing dosages of continuously infused arginine vasopressin (AVP) in an autoperfused, innervated jejunal...
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Effects of epinephrine on intestinal oxygen supply and Mucosal Tissue oxygen tension in pigs.
Critical care medicine, 2001Co-Authors: Natalie Salak, Birgit Schwarz, Werner Pajk, Hanno Ulmer, Hans Knotzer, Hubert Hofstötter, Andreas Mayr, Burkhard Labeck, Reinhold Kafka, Norbert MutzAbstract:OBJECTIVE To study the effects of increasing dosages of epinephrine given intravenously on intestinal oxygen supply and, in particular, Mucosal Tissue oxygen tension in an autoperfused, innervated jejunal segment. DESIGN Prospective, randomized experimental study. SETTING Animal research laboratory. SUBJECTS Domestic pigs. INTERVENTIONS Sixteen pigs were anesthetized, paralyzed, and normoventilated. A small segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension was measured by using Clark-type surface oxygen electrodes. Microvascular hemoglobin oxygen saturation and microvascular blood flow (perfusion units) were determined by Tissue reflectance spectrophotometry and laser-Doppler velocimetry. Systemic hemodynamics, mesenteric-venous acid-base and blood gas variables, and systemic acid-base and blood gas variables were recorded. Measurements were performed after a resting period and at 20-min intervals during infusion of increasing dosages of epinephrine (n = 8; 0.01, 0.05, 0.1, 0.5, 1, and 2 microg x kg(-1) x min(-1)) or without treatment (n = 8). In addition, arterial and mesenteric-venous lactate concentrations were measured at baseline and at 60 and 120 mins. MEASUREMENTS AND MAIN RESULTS Epinephrine infusion led to significant tachycardia; an increase in cardiac output, systemic oxygen delivery, and oxygen consumption; and development of lactic acidosis. Epinephrine significantly increased jejunal microvascular blood flow (baseline, 267 +/- 39 perfusion units; maximum value, 443 +/- 35 perfusion units) and Mucosal oxygen tension (baseline, 36 +/- 2.0 torr [4.79 +/- 0.27 kPa]; maximum value, 48 +/- 2.8 torr [6.39 +/- 0.37 kPa]) and increased hemoglobin oxygen saturation above baseline. Epinephrine increased mesenteric venous lactate concentration (baseline, 2.9 +/- 0.6 mmol x L(-1); maximum value, 5.5 +/- 0.2 mmol x L(-1)) without development of an arterial-mesenteric venous lactate concentration gradient. CONCLUSIONS Epinephrine increased jejunal microvascular blood flow and Mucosal Tissue oxygen supply at moderate to high dosages. Lactic acidosis that develops during infusion of increasing dosages of epinephrine is not related to development of gastrointestinal hypoxia.
Jonathan Segal - One of the best experts on this subject based on the ideXlab platform.
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iddf2019 abs 0028 Mucosal Tissue short chain fatty acids contribute to prediction of pouchitis in restorative proctocolectomy
Gut, 2019Co-Authors: Jonathan Segal, M Sarafian, Alexandros Pechlivanis, Ivan Jose Serrano Contreras, Jerusa Brignardello, Yihharn Siaw, Lucia Braz, Clark Susan, Holmes Elaine, Hart AilsaAbstract:Background Restorative proctocolectomy is a surgical option in patients with ulcerative colitis who become refractory to medical therapy. Various studies have implicated SCFA in both the development of IBD and flares of IBD. Furthermore, it has been shown that SCFA concentrations are significantly lower in faecal samples from patients with pouchitis when compared with healthy controls. Our study aimed to assess longitudinal changes in SCFA that occur in a pouch to determine if they can predict or are associated with the development of pouchitis. To date no study has analysed short chain fatty acids in Mucosal biopsy Tissue from these patients. Methods Patients who underwent restorative proctocolectomy at a single centre underwent pouchoscopy at the time of restoration of continuity and then every 6 months for a year. Biopsies were retrieved from the pouch body. Pouchitis was defined using the pouch disease activity index. The development of pouchitis was assessed at 6 and 12 months.SCFA were measured using an Agilent 7000C Triple Quadrupole GC/MS-MS System. Simca was used for multivariate analysis and T-tests were used for univariate analysis. Results There were 56 biopsy samples. There were 22 patients (17 males); 16 UC and 6 FAP patients. Median age of the cohort was 40 years (range 20–60 years). Of the UC patients four developed pouchitis within one year. Comparing UC patients at the time of closure of ileostomy, there were significant decreases in caproic acid (4674uM vs 12217uM p Conclusions A decrease in SCFA found in the Mucosal Tissue at time of closure of ileostomy may predict onset of pouchitis within a year. This study is the first to demonstrate that SCFA can be analysed from biopsies. Future studies need to determine factors that may contribute to Tissue SCFA levels which may help reduce the incidence of pouchitis.
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pth 118 Mucosal Tissue short chain fatty acids contribute to prediction of pouchitis in restorative proctocolectomy
Gut, 2019Co-Authors: Jonathan Segal, M Sarafian, Alexandros Pechlivanis, Ivan Jose Serrano Contreras, Jerusa Brignardello, Yihharn Siaw, Lucia Braz, S K Clark, Elaine Holmes, Ailsa HartAbstract:Background Restorative proctocolectomy is a surgical option in patients with ulcerative colitis who become refractory to medical therapy. Short chain fatty acids (SCFA) are organic fatty acids with 1–6 carbons which arise from bacterial metabolism from carbohydrates entering the colon. Various studies have implicated SCFA in both the development of IBD and flares of IBD. Furthermore, it has been shown that SCFA concentrations are significantly lower in faecal samples from patients with pouchitis when compared with healthy controls. Our study aimed to assess longitudinal changes in SCFA that occur in a pouch to determine if they can predict or are associated with the development of pouchitis. To date no study has analysed short chain fatty acids in Mucosal biopsy Tissue from these patients. Methods Patients who underwent restorative proctocolectomy at a single centre underwent pouchoscopy at the time of restoration of continuity and then every 6 months for a year. Biopsies from the pouch were retrieved from the pouch body. Pouchitis was defined using the pouch disease activity index. The development of pouchitis was assessed at months 6 and 12 months. Biopsies samples were snap frozen at time of biopsy and stored in -80°C. Samples were thawed and weighed. Sterile water and Methyl tertiary-butyl ether with internal standard (IS) were added with a ratio of 20 mg of sample:50µL of H20:250µL of MTBE and IS with a further 4µL of hydrochloric acid added to each sample. 30µL of the polar phase was then placed into silanized Eppendorf tubes. 150µL of derivatiser was added to each sample and the cap of the tube applied immediately. These were then incubated for 45 minutes at 60°C in an oven. 70µL from the silanised vial was placed into vial inserts and analysed in the gas chromatography mass spectrometry machine. (GC-MS). SCFA were measured using an Agilent 7000C Triple Quadrupole GC/MS-MS System according to a previously published method. Simca was used for multivariate analysis and T-tests were used for univariate analysis. Results There were 56 biopsy samples. There were 22 patients (17 males); 16 UC and 6 FAP patients with longitudinal follow up. The median age of the cohort was 40 years (range 20–60 years). Of the UC patients four developed pouchitis within one year. When comparing UC patients at the time of closure of ileostomy, there were there were significant decreases in caproic acid (4674µM vs 12217µM p Conclusion The study has suggested that a decrease in SCFA found in the Mucosal Tissue at time of closure of ileostomy may predict onset of pouchitis within a year. This study is the first to demonstrate that SCFA can be analysed from biopsies. Future studies need to determine factors that may contribute to Tissue SCFA levels which may help develop a potential therapeutic target to optimise and potentially reduce the incidence of pouchitis.
Werner Pajk - One of the best experts on this subject based on the ideXlab platform.
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Arginine-vasopressin attenuates beneficial norepinephrine effect on jejunal Mucosal Tissue oxygenation during endotoxinaemia
British journal of anaesthesia, 2009Co-Authors: S. Maier, Walter R. Hasibeder, Werner Pajk, Hanno Ulmer, Hans Hausdorfer, C. Hengl, Bettina Wurzinger, Hans KnotzerAbstract:Background The objective of the present study was to investigate the effects of increasing doses of norepinephrine (NE) with or without arginine-vasopressin (AVP) on intestinal oxygen supply and jejunal Mucosal Tissue oxygen tension in an acute endotoxic pig model. Methods In this prospective, randomized, experimental study on 24 domestic pigs, jejunal Mucosal Tissue P o 2 (P o 2muc) was measured using two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular haemoglobin (HbO2j) was determined by Tissue reflectance spectrophotometry. Systemic haemodynamic variables, mesenteric-venous and systemic acid–base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli lipopolysaccharide (LPS) administration, and at 20 min intervals during incremental NE infusion (0.05, 0.1, 0.5, 1.0, and 2 µg kg−1 min−1, respectively) with 57 mU kg−1 h−1 AVP (n=8; NE+AVP group) or without (n=8; NE group); or infusion of an equal amount of normal saline (n=8; CON group). Results LPS infusion led to a significant (P o 2muc and HbO2j. Both NE and NE+AVP increased arterial pressure, cardiac output, and mesenteric artery blood flow. Concomitant to an increase in systemic oxygen delivery, NE improved P o 2muc and HbO2j. NE alone was superior in restoration of P o 2muc when compared with NE+AVP. Conclusions Both NE and NE+AVP improved global haemodynamics and systemic oxygen transport variables when compared with control animals in an acute endotoxic pig model. NE improved jejunal P o 2muc at all dosages. NE effects were significantly blunted by simultaneous administration of AVP.
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Epoprostenol improves Mucosal Tissue oxygen tension in an acute endotoxemic pig model.
Shock (Augusta Ga.), 2009Co-Authors: S. Maier, Walter R. Hasibeder, Werner Pajk, Hanno Ulmer, Hans Hausdorfer, Christian Torgersen, Josef Klocker, Hans KnotzerAbstract:ABSTRACT The objective of the present study was to determine the effects of increasing dosages of continuously infused epoprostenol (PGI), a prostacyclin analog, on intestinal oxygen supply and jejunal Mucosal Tissue oxygen tension in an acute endotoxic pig model. Jejunal Mucosal Tissue PO2, oxygen saturation of jejunal microvascular hemoglobin, and gut microvascular blood flow were investigated. Systemic hemodynamic variables, mesenteric-venous and systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli LPS administration, and at 20-min intervals during incremental PGI infusion (n = 8; 25, 50, 100, and 200μg·kg−1·h−1, respectively); or infusion of an equal amount of isotonic sodium chloride solution (n = 7). LPS infusion led to a significant decrease in Mucosal Tissue oxygen tension and microvascular hemoglobin oxygen saturation. Epoprostenol infusion led to a significant, dose-dependent increase in cardiac index and systemic oxygen delivery. Mucosal Tissue oxygen tension and microvascular hemoglobin oxygen saturation increased after PGI administration and even returned to more-than-baseline values. Continuously infused PGI increased intestinal hemoglobin oxygen saturation and Mucosal Tissue oxygen tension in a dose-dependent manner mainly due to an increase in villus blood flow in this acute endotoxic pig model.
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Arginine vasopressin reduces intestinal oxygen supply and Mucosal Tissue oxygen tension.
American journal of physiology. Heart and circulatory physiology, 2005Co-Authors: Hans Knotzer, Werner Pajk, Hanno Ulmer, Stephan E. Maier, Ruth Ladurner, Axel Kleinsasser, Volker Wenzel, Martin W. Dünser, Walter R. HasibederAbstract:We investigated intestinal oxygen supply and Mucosal Tissue Po2 during administration of increasing dosages of continuously infused arginine vasopressin (AVP) in an autoperfused, innervated jejunal...
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Effects of epinephrine on intestinal oxygen supply and Mucosal Tissue oxygen tension in pigs.
Critical care medicine, 2001Co-Authors: Natalie Salak, Birgit Schwarz, Werner Pajk, Hanno Ulmer, Hans Knotzer, Hubert Hofstötter, Andreas Mayr, Burkhard Labeck, Reinhold Kafka, Norbert MutzAbstract:OBJECTIVE To study the effects of increasing dosages of epinephrine given intravenously on intestinal oxygen supply and, in particular, Mucosal Tissue oxygen tension in an autoperfused, innervated jejunal segment. DESIGN Prospective, randomized experimental study. SETTING Animal research laboratory. SUBJECTS Domestic pigs. INTERVENTIONS Sixteen pigs were anesthetized, paralyzed, and normoventilated. A small segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension was measured by using Clark-type surface oxygen electrodes. Microvascular hemoglobin oxygen saturation and microvascular blood flow (perfusion units) were determined by Tissue reflectance spectrophotometry and laser-Doppler velocimetry. Systemic hemodynamics, mesenteric-venous acid-base and blood gas variables, and systemic acid-base and blood gas variables were recorded. Measurements were performed after a resting period and at 20-min intervals during infusion of increasing dosages of epinephrine (n = 8; 0.01, 0.05, 0.1, 0.5, 1, and 2 microg x kg(-1) x min(-1)) or without treatment (n = 8). In addition, arterial and mesenteric-venous lactate concentrations were measured at baseline and at 60 and 120 mins. MEASUREMENTS AND MAIN RESULTS Epinephrine infusion led to significant tachycardia; an increase in cardiac output, systemic oxygen delivery, and oxygen consumption; and development of lactic acidosis. Epinephrine significantly increased jejunal microvascular blood flow (baseline, 267 +/- 39 perfusion units; maximum value, 443 +/- 35 perfusion units) and Mucosal oxygen tension (baseline, 36 +/- 2.0 torr [4.79 +/- 0.27 kPa]; maximum value, 48 +/- 2.8 torr [6.39 +/- 0.37 kPa]) and increased hemoglobin oxygen saturation above baseline. Epinephrine increased mesenteric venous lactate concentration (baseline, 2.9 +/- 0.6 mmol x L(-1); maximum value, 5.5 +/- 0.2 mmol x L(-1)) without development of an arterial-mesenteric venous lactate concentration gradient. CONCLUSIONS Epinephrine increased jejunal microvascular blood flow and Mucosal Tissue oxygen supply at moderate to high dosages. Lactic acidosis that develops during infusion of increasing dosages of epinephrine is not related to development of gastrointestinal hypoxia.
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Inotropic treatment and intestinal Mucosal Tissue oxygenation in a model of porcine endotoxemia.
Critical care medicine, 1997Co-Authors: R. Germann, M. Haisjackl, Johannes Bonatti, Eva M. Gruber, Birgit Schwarz, Werner Pajk, Hans Hausdorfer, Engelbert Deusch, Stefan Meusburger, Bernhard FurtnerAbstract:Objective: To evaluate the dose-related effects of dopamine, dopexamine, and dobutamine on intestinal Mucosal Tissue oxygenation following short-time infusion of Escherichia coli lipopolysaccharide, which has previously been shown to decrease Mucosal Tissue oxygenation by 60% of control values. Design: Prospective, randomized, unblinded study. Setting: Animal research laboratory. Subjects: Anesthetized, mechanically ventilated domestic pigs. Interventions: Pigs were infused with 2 μg/kg of E. coli lipopolysaccharide over 20 mins via the superior mesenteric artery. Pulmonary artery occlusion pressure was maintained near 15 mm Hg, using a mixed infusion regimen of Ringer's lactate solution and hydroxyethyl starch. Following endotoxemia, a small segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. The control group (n = 7) received no further interventions. Pigs in the dopamine (n = 7), dopexamine (n = 7), and dobutamine (n = 7) groups were infused with 2.5, 5, 10, and 20 μg/kg/min of the respective drug via a central venous catheter. Measurements and Main Results: Systemic hemodynamics as well as systemic, mesenteric, and femoral blood gas variables were measured using an arterial, a thermodilution pulmonary artery, a superior mesenteric venous, and a femoral venous catheter. Jejunal Mucosal Tissue Po 2 was measured by means of two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal Mucosal microvascular hemoglobin was determined by Tissue reflectance spectrophotometry. Infusion of endotoxin resulted in pulmonary hypertension. Systemic hemodynamics remained unchanged except for brief decreases in cardiac output and arterial blood pressure. Dopamine, dopexamine, and dobutamine increased systemic oxygen delivery in a dose-related manner by 80% (p