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  • 1.
    Castegren, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i D län (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Söderberg, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Eriksson, Mats
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Differences in Organ Dysfunction in Endotoxin Tolerant Pigs Under Intensive Care Exposed to a Second Hit of Endotoxin2012Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 37, nr 5, s. 501-510Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endotoxin tolerance is a well-studied phenomenon associated with a reduced inflammatory response. In the switch from an inflammatory to an anti-inflammatory response in clinical sepsis the concept of endotoxin tolerance is of obvious interest. However, only limited data exist regarding the effect of endotoxin tolerance on organ dysfunction and, therefore, this was investigated in a porcine intensive care sepsis model. Twenty-seven healthy pigs, including nine control animals, were included in the study. Twelve pigs pre-exposed to 24 h of intravenous endotoxin infusion and intensive care and six unexposed pigs were given either a high- or low-dose endotoxin challenge for 6 h. Inflammatory, circulatory, hypoperfusion and organ dysfunction parameters were followed. The inflammatory responses as well as parameters representing circulation, hypoperfusion, cardiac and renal function were all markedly attenuated in animals pre-exposed to endotoxin and intensive care as compared with animals not pre-exposed. In animals pre-exposed to endotoxin and given the high-dose of endotoxin challenge, deterioration in pulmonary function was equal to or even worse than in animals not pre-exposed.In contrast to the overall protective effect of endotoxin tolerance observed in other organ systems, the lungs of endotoxin tolerant animals demonstrated an increased responsiveness to high-dose endotoxin challenge.

  • 2.
    Lipcsey, Miklos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Pischke, Soeren E
    Department of Immunology, University of Oslo, 0450 Oslo, Norway..
    Kuitunen, Anne
    Department of Intensive Care, University of Tampere and Tampere University Hospital, Tampere, Finland..
    Flaatten, Hans
    Department of Clinical Medicine, Haukeland University Hospital, UiB Bergen, Norway..
    De Geer, Lina
    Department of Anaesthesiology and Intensive Care, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Chew, Michelle S
    Department of Anaesthesiology and Intensive Care, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Bendel, Stepani
    Department of intensive care, Kuopio University Hospital, Kuopio, Finland..
    Kawati, Rafael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Mollnes, Tom Eirik
    Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway..
    Tønnessen, Tor Inge
    Division of Emergencies and Critical Care, Oslo University Hospital 0450 Oslo, and Institute of Clinical Medicine University of Oslo, 0316 Oslo, Norway..
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Endotoxin Removal in Septic Shock with the Alteco® LPS Adsorber was Safe But Showed No Benefit Compared to Placebo in the Double-Blind Randomized Controlled Trial - the Asset Study.2019Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco® LPS Adsorber for LPS removal in early Gram-negative septic shock was feasible and safe. Also, effect on endotoxin level, inflammatory response and organ function were assessed.

    METHODS: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate thirty-two septic shock patients with abdominal or urogenital focus to LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS-binding. The study treatment was initiated within 12 hours of inclusion and given for six hours daily on first two days. LPS was measured in all patients.

    RESULTS: The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups.

    CONCLUSIONS: In a small cohort of patients with presumed Gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared to a sham device was seen when using a LPS adsorber in addition to standard care.

    TRIAL REGISTRATION: Clinicaltrials.gov NCT02335723. Registered: November 28, 2014.

  • 3.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Effect of the Administration Rate on the Biological Responses To A Fixed Dose of Endotoxin in the Anesthetized Pig2008Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 29, nr 2, s. 173-180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There have been difficulties to demonstrate a relationship between endotoxin concentration and clinical response. One hypothesis for this difficulty might be that a fast increase in endotoxin concentration elicits a stronger biological response than a more gradual one of the same dose. The aim of the present study was to investigate the existence of such a response. Eighteen randomized pigs were given the same amount of endotoxin either with an initial infusion rate of 4 μg kg-1 h-1, which after 1 h was tapered to 0.5 μg kg-1 h-1, and after 2 h to 0.063 μg kg-1 h-1 (group I), or with a reverse escalating order with the lowest infusion rate given first (group II). After 3 h, the endotoxin infusion was stopped, and the pigs were observed for another 3 h. The responses in TNF-α, core temperature, leukocytes, platelets, MAP, left ventricular stroke work index, mixed venous saturation, base excess, pH, and pulmonary compliance were greater in group I than in group II, whereas the IL-6 response did not differ between groups. The biological responses of inflammation, hypotension, hypoperfusion, and organ dysfunction are increased if the organism is exposed to a fixed amount of endotoxin more quickly.

    Abbreviations - BE-Base excess; CI-Cardiac index; DO2-Oxygen delivery; Fio2-fraction of oxygen; Hb-Hemoglobin; LVSWI-Left ventricular stroke work index; MPAP-Mean pulmonary arterial pressure; Paco2-Arterial partial pressure of carbon dioxide; Pao2-Arterial partial pressure of oxygen; pH-Potentia Hydrogenii; SEM-Standard error of the mean; Svo2-Venous oxygen saturation

  • 4. Ljungdahl, M
    et al.
    Rasmussen, I
    Haglund, U
    Intestinal blood flow and intramucosal pH in experimental peritonitis.1999Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 11, nr 1, s. 44-50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS: Experimental peritonitis causes gut intramucosal acidosis indicating intramucosal ischemia. However, tissue acidosis may reflect other conditions than ischemia. An increased mucosal-arterial Pco2 difference ( Pco2-gap) is suggested to be a more adequate measure of tissue ischemia than intramucosal pH (pHi). This study was performed to elucidate whether keeping cardiac index (CI) and splanchnic blood flow normal or supranormal by administration of colloids and an inotropic drug could prevent the acidosis as well as reduce the Pco2-gap. A secondary aim was to study to what degree the low pHi in peritonitis really reflects ischemia.

    SUBJECTS: 24 anesthetized pigs (18-27 kg) divided into four groups.

    MODELS: A Swan-Ganz catheter, transonic flow meters and catheters for blood sampling were applied. pHi was calculated using tonometry. Standardized fecal peritonitis was induced, except in controls. One peritonitis group was given dextran (Group P(DEX)) and another in addition dobutamine (Group PDOB) to keep CI normal or supranormal, respectively.

    RESULTS: After 4 h, a significant drop in pHi was found in all peritonitis groups, most pronounced in untreated peritonitis (to 7.09+/-.02). Corresponding values in Group P(DEX) and Group P(DOB) were 7.22+/-.03 and 7.22+/-.01, respectively, and in controls 7.30+/-.02. The Pco2-gap and the mucosal-arterial [H+] difference ([H+]-gap) increased significantly in untreated peritonitis but did not increase in groups given dextran and dextran + dobutamine.

    CONCLUSION: Maintaining CI in peritonitis attenuated the reduction in pHi and prevented the increased Pco2- and [H+]-gap. It seems justified from these data to conclude that the somewhat reduced pHi in treated peritonitis groups did not reflect tissue ischemia.

  • 5. Ljungdahl, M
    et al.
    Rasmussen, I
    Raab, Y
    Hillered, L
    Haglund, U
    Small intestinal mucosal pH and lactate production during experimental ischemia-reperfusion and fecal peritonitis in pigs.1997Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 7, nr 2, s. 131-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate mucosal pH and lactate production in a porcine model of ischemia/reperfusion and sepsis using both tonometry and a technique for segmental intestinal perfusion. Eighteen pigs (17-23 kg) were anesthetized and mechanically ventilated. They were divided into three groups and followed for 4 h. Group C (n = 6) served as controls. In the ischemia/reperfusion group (I/R; n = 6), the superior mesenteric artery was totally occluded for 60 min. In group P (n = 6), sepsis was induced by fecal peritonitis. Cardiac index (CI) was determined by thermodilution and blood flow in the superior mesenteric artery (QSMA), using a Transonic flow probe. Intramucosal pH (pHi) was calculated using tonometry. A special balloon tube for segmental perfusion was introduced in the midileum for lactate measurement. Lactate and oxygen saturation were measured in arterial blood and in the superior mesenteric vein. CI, QSMA, pHi, and lactate in blood and perfusate remained unchanged in controls. Occlusion of intestinal blood flow induced a fall in pHi from 7.28 +/- .02 to 6.76 +/- .04, a marked rise in lactate in the perfusate, and an increased arteriovenous lactate difference. During reperfusion, pHi tended to return to baseline values. Lactate in the perfusate and the arteriovenous lactate difference decreased. In sepsis there was a continuous reduction in CI and QSMA to 45 +/- 13% and 40 +/- 20% of baseline, respectively. pHi decreased moderately from 7.22 +/- .09 to 6.98 +/- .25. Lactate remained unchanged in blood and perfusate. Microscopic mucosal injury was observed in all animals subjected to ischemia/reperfusion and in three of six pigs in group P. A good association between pHi and lactate production was seen in ischemia/reperfusion. However, in sepsis, lactate in superior mesenteric venous blood or in intestinal perfusate did not increase, despite the fall in pHi. The mechanism causing ischemic mucosal injury has different characteristics in sepsis and in ischemia caused by arterial occlusion.

  • 6. Rasmussen, I
    et al.
    Hillered, L
    Ungerstedt, U
    Haglund, U
    Detection of liver ischemia using microdialysis during experimental peritonitis in pigs.1994Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 1, nr 1, s. 60-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The liver oxygen delivery (DO2) and consumption (VO2) were measured in a porcine model of septic shock induced by fecal peritonitis. Lactate and hypoxanthine were simultaneously monitored in hepatic extracellular fluid and in central venous blood using a microdialysis technique. Animals were divided into a control group (n = 6) and a peritonitis group (n = 6). Peritonitis was induced by installation of a standardized amount of autologous feces into the abdominal cavity. The animals were followed for 5 h. The changes in the liver during peritonitis were, a decreased DO2, a increased, maintained, or decreased VO2, an increased oxygen extraction, and a loss of net hepatic lactate uptake. Parallel to these changes, systemic lactic acidosis developed. Intrahepatic lactate and hypoxanthine increased during peritonitis reflecting liver ischemia. The increase of these metabolites was seen concomitantly in the liver and in central venous blood. There was a wide variability of the individual response to the septic challenge among the animals. The limited hepatic oxygen delivery, and the increased needs for oxygen led to flow-dependent oxygen consumption, and signs of liver ischemia in severe sepsis. Intrahepatic and intravenous microdialysis may be useful for monitoring of the individual time course of hepatic and systemic ischemia in sepsis.

  • 7.
    Semenas, Egidijus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sharma, Hari Shanker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Nozari, Ala
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Neuroprotective effects of 17-beta-estradiol after hypovolemic cardiac arrest in immature piglets: the role of nitric oxide and peroxidation2011Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 36, nr 1, s. 30-37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We recently reported that cerebral and cardiac injuries are mitigated in immature female piglets after severe hemorrhage with subsequent cardiac arrest (CA) Female sex was also associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (nNOS). In the current study, we tested the hypothesis that exogenously administered 17β-estradiol (E2) can improve neurological outcome by NOS modulation. Thirty nine sexually immature piglets were bled to a mean arterial pressure of 35 mmHg over 15 min. Fifty μg/kg of E2 was then administered to 10 male and 10 female animals (estradiol group), while control animals (n=10 males and 9 females) received equal volume of normal saline. The animals were then subjected to ventricular fibrillation (4 min) followed by up to 15 min of open chest CPR. Vasopressin 0.4 U/kg and amiodarone 0.5 mg/kg were given and 3 ml/kg of 7.5% saline with 6% dextran was administered over 20 min. All surviving animals were euthanized after 3hr and their brains examined for histological injury and NOS expression. No significant differences were observed in survival or hemodynamics between the groups. Compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption and a mitigated neuronal injury. There was a significant correlation between nNOS and iNOS levels and neuronal injury. Interestingly estradiol attenuated cerebral damage (including lower activation of nNOS and iNOS) both in male and female piglets. In conclusion, in our immature piglets model of hypovolemic cardiac arrest, E2 down-regulates iNOS and nNOS expression and results in decreased BBB permeability disruption and smaller neuronal injury.

  • 8.
    van Griensven, Martijn
    et al.
    Tech Univ Munich, Klinikum Rechts Isar, Dept Trauma Surg, Expt Trauma Surg, Munich, Germany.
    Ricklin, Daniel
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA;Univ Basel, Dept Pharmaceut Sci, Basel, Switzerland.
    Denk, Stephanie
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany.
    Halbgebauer, Rebecca
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany.
    Braun, Christian K.
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany.
    Schultze, Anke
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany.
    Hoenes, Felix
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany.
    Koutsogiannaki, Sofia
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.
    Primikyri, Alexandra
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.
    Reis, Edimara
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.
    Messerer, David
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany.
    Hafner, Sebastian
    Univ Ulm, Inst Anaesthesiol Pathophysiol & Proc Dev, Ulm, Germany.
    Radermacher, Peter
    Univ Ulm, Inst Anaesthesiol Pathophysiol & Proc Dev, Ulm, Germany.
    Biglarnia, Ali-Reza
    Lund Univ, Malmo Univ Hosp, Dept Transplantat, Lund, Sweden.
    Resuello, Ranillo R. G.
    Simian Conservat Breeding & Res Ctr SICONBREC, Makati, Philippines.
    Tuplano, Joel V.
    Simian Conservat Breeding & Res Ctr SICONBREC, Makati, Philippines.
    Mayer, Benjamin
    Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany.
    Nilsson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lambris, John D.
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.
    Huber-Lang, Markus
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany.
    PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK2019Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 51, nr 1, s. 78-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of immune, coagulation, and organ dysfunction often resulting in a poor clinical outcome. Imbalanced complement activation is intricately associated with the molecular danger response and organ damage after HS. Thus, inhibition of the central complement component C3 as turnstile of both inflammation and coagulation is hypothesized as a rational strategy to improve the clinical course afterHS. Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated nonhuman primates (NHP; cynomolgusmonkeys) received a pressure-controlled severe HS (60min at mean arterial pressure 30 mmHg) with subsequent volume resuscitation. Thirty minutes after HS, animals were randomly treated with either an analog of the C3 inhibitor compstatin (i.e., Cp40) in saline (n =4) or with saline alone (n =4). The observation period lasted 300 min after induction of HS. We observed improved kidney function in compstatin Cp40-treated animals after HS as determined by improved urine output, reduced damage markers and a tendency of less histopathological signs of acute kidney injury. Sham-treated animals revealed classical signs ofmucosal edema, especially in the ileum and colon reflected by worsened microscopic intestinal injury scores. In contrast, Cp40-treated HS animals exhibited only minor signs of organ edema and significantly less intestinal damage. Furthermore, early systemic inflammation and coagulation dysfunction were both ameliorated by Cp40. The data suggest that therapeutic inhibition of C3 is capable to significantly improve immune, coagulation, and organ function and to preserve organ-barrier integrity early after traumatic HS. C3-targeted complement inhibition may therefore reflect a promising therapeutic strategy in fighting fatal consequences of HS.

  • 9.
    van Griensven, Martijn
    et al.
    Tech Univ Munich, Expt Trauma Surg, Munich, Germany..
    Ricklin, Daniel
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.;Univ Basel, Dept Pharmaceut Sci, Basel, Switzerland..
    Denk, Stephanie
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany..
    Halbgebauer, Rebecca
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany..
    Braun, Christian K.
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany..
    Schultze, Anke
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany..
    Hönes, Felix
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany..
    Koutsogiannaki, Sofia
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA..
    Primikyri, Alexandra
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA..
    Reis, Edimara
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA..
    Messerer, David
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany..
    Hafner, Sebastian
    Univ Ulm, Inst Anaesthesiol Pathophysiol & Proc Dev, Ulm, Germany..
    Radermacher, Peter R.
    Univ Ulm, Inst Anaesthesiol Pathophysiol & Proc Dev, Ulm, Germany..
    Resuello, Ranillo R. G.
    Simian Conservat Breeding & Res Ctr SICONBREC, Makati, Philippines..
    Tuplano, Joel V.
    Simian Conservat Breeding & Res Ctr SICONBREC, Makati, Philippines..
    Nilsson Ekdahl, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lambris, John D.
    Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA..
    Huber-Lang, Markus S.
    Univ Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany..
    PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK2018Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 49, nr 6, Suppl. 1, s. 117-118, artikel-id P183Artikel i tidskrift (Övrigt vetenskapligt)
  • 10.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Engström, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Maripuu, Enn
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Widström, Charles
    Department of Medical Physics, University Hospital, Uppsala, Sweden.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin: A Randomized Controlled Trial in the Endotoxemic Pig2017Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 47, nr 4, s. 514-519Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL x kg 5% albumin labeled with Technetium-99m, either as a rapid 15-minute bolus (Bolus group, n = 16) or as a 2-hour (h) infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney and lung was analyzed post-mortem.The plasma area under the curve (AUC) activity0-6h was 4.4 ± 0.9 x 10 in the Bolus group and 4.4 ± 1.1 x 10 counts x min x mL x h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.

  • 11.
    von Seth, Magnus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial2015Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 43, nr 6, s. 604-611Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from Gram-negative multi-resistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have previously not been explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison to doxycycline and placebo.

    METHODS: Eighteen pigs were randomized to receive tigecycline 100 mg, doxycycline 200 mg or placebo and subjected to 6 h endotoxin infusion at 0.5 μg x kg x h. Markers of inflammation, nitric oxide (NO) production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism and acid-base parameters were monitored.

    RESULTS: Peak plasma tumor necrosis alpha (TNF-α) was lower in the doxycycline group (P=0.031) but not in the tigecycline group (P=0.86) compared to placebo with geometric mean plasma concentrations of 16, 79 and 63 ng x ml, respectively. Mean arterial pressure was higher 4-6 h in the tigecycline group with values at 6 h of 107± 9 mmHg compared to the placebo and doxycycline groups (85 ± 27 mmHg and 90 ± 32 mmHg, respectively) (P=0.025). The white blood cell and the neutrophil granulocyte counts were less reduced in the doxycycline group, but not in the tigecycline group at 4-6 h (P=0.009 and p=0.019, respectively). Other markers of inflammation, organ dysfunction, tissue metabolism and acid-base parameters were unaffected by tigecycline.

    CONCLUSIONS: Consistent with known anti-inflammatory properties, doxycycline yielded decreased TNF-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion.

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