| 1. |
- Bansch, Peter, et al.
(författare)
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A Model for Evaluating the Effects of Blunt Skeletal Muscle Trauma on Microvascular Permeability and Plasma Volume in the Rat
- 2010
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Ingår i: Shock. - 1540-0514. ; 33:4, s. 399-404
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the present study was to develop an experimental model suitable for studying the effects of a nonhemorrhagic soft tissue trauma on plasma volume (PV) and microvascular permeability. Anesthetized Sprague-Dawley rats were exposed to a sham procedure or a laparotomy followed by a standardized trauma to the abdominal rectus muscle. We evaluated the effects of trauma on transcapillary escape rate and on PV (3 h after trauma) using I-125-albumin as tracer and on edema formation in the traumatized muscle with a wet- versus dry- weight method. The effects of the trauma on the cytokines IFN-gamma, IL-4, IL-6, IL-10, and TNF-alpha were investigated 1 and 3 h after trauma in a separate group. Transcapillary escape rate was 13.9% per hour in the sham animals compared with 18.5% per hour in the traumatized animals (P < 0.05). Because arterial and venous blood pressures were not altered by the trauma, the change in transcapillary escape rate most likely reflects a change in microvascular permeability. Plasma volume decreased from 42 mL/kg at baseline to 31 mL/kg at the end of the experiments (P < 0.05) in the trauma group, whereas PV remained unchanged in the sham group. Only 15% of the PV loss could be referred to edema in the traumatized muscle. Trauma induced a significant increase in IL-6 and IL-10 after 1 h. We conclude that the present nonhemorrhagic trauma induces an increase in microvascular permeability in the traumatized tissue and in other parts of the body, resulting in hypovolemia. The model may be used for the evaluation of different therapeutic interventions aimed at the correction of hypovolemia.
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| 2. |
- Bansch, Peter, et al.
(författare)
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Changes in the sublingual microcirculation during major abdominal surgery and post-operative morbidity.
- 2014
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 58:1, s. 89-97
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about perioperative microcirculatory changes during major abdominal surgery, and the main objectives of this study were to evaluate perioperative microcirculatory alterations in this setting, and if changes in microcirculatory parameters are associated with post-operative morbidity and/or with changes in parameters reflecting oxygen delivery.
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| 3. |
- Bansch, Peter, et al.
(författare)
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Effect of charge on microvascular permeability in early experimental sepsis in the rat.
- 2011
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 82, s. 339-345
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Tidskriftsartikel (refereegranskat)abstract
- A key feature of sepsis is hypovolemia due to increased microvascular permeability. It has been suggested that the negative charge of albumin and of the endothelial glycocalyx is important for maintenance of the normally low permeability for albumin. Here we tested the hypothesis that charge effects contribute to the increased permeability in sepsis. Transcapillary escape rate (TER) and initial distribution volume for (125)I-labeled bovine serum albumin (BSA, isoelectric point pH 4.6) and for (131)I-labeled charge modified BSA (cBSA, average isoelectric point, pH 7.1) was measured 3h after sepsis was induced by cecal ligation and incision (CLI) (n=11) and in control animals (n=12). The importance of charge for permeability in sepsis was estimated by comparing the ratio between TER for cBSA and TER for BSA during control conditions to that after CLI. Plasma concentration of the glycocalyx component glycosaminoglycans (GAGs) was measured in separate control and CLI animals. The initial distribution volume for BSA and cBSA in control animals was 38±3ml/kg and 47±4mL/kg and decreased by 17% and 19%, respectively, following CLI. TER for BSA increased from 16.7±4.1% in the controls to 20.1±1.9% following CLI. Corresponding values for cBSA were 26.7±5.6% and 29.8±3.5%, respectively. The ratio between TER for cBSA and TER for BSA was 1.62±0.1 in the control group and 1.49±0.1 following CLI (p<0.05). Plasma GAG concentrations were higher in CLI animals than in the control group. We conclude that CLI induce hypovolemia secondary to increased microvascular permeability. Negative charge contributes to the normally low permeability of albumin and the importance of charge is decreased in early experimental sepsis. The observed charge effects are associated with CLI-induced breakdown of the glycocalyx.
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| 4. |
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| 5. |
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| 6. |
- Bansch, Peter, et al.
(författare)
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Prostacyclin reduces plasma volume loss after skeletal muscle trauma in the rat.
- 2012
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Ingår i: Journal of Trauma and Acute Care Surgery. - 2163-0755.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Trauma induces transcapillary leakage of fluid and proteins because of increased microvascular permeability. Based on studies showing that prostacyclin (PGI2) has permeability-reducing properties, in the present study, we investigated whether PGI2 reduces plasma volume (PV) loss after a nonhemorrhagic trauma. METHODS: The study was performed on anesthetized Sprague-Dawley rats exposed to a controlled standardized blunt trauma to the abdominal rectus muscle. Thereafter, the animals were randomized to treatment with either PGI2 (2 ng/kg per minute) or 0.9% NaCl. PV was estimated before and 3 hours after the trauma using I-albumin as tracer. In separate experiments, the transcapillary escape rate of I-albumin was calculated and plasma concentrations of cytokines were measured after both treatments. RESULTS: Average PV at baseline was 41.6 mL/kg ± 2.5 mL/kg and 42.3 mL/kg ± 1.7 mL/kg in the PGI2 and NaCl animals, respectively. PV was decreased by 22% ± 8% in the NaCl animals and by 11% ± 9% in the PGI2 animals 3 hours after the trauma (p < 0.05). Trauma induced a decrease in mean arterial blood pressure and an increase in hematocrit in both groups. There were no differences in urine production and mean arterial blood pressure between the PGI2 and NaCl animals. The transcapillary escape rate for albumin was calculated for one hour starting 30 minutes after the trauma and was 15.1% ± 2.4% per hour in the PGI2 animals and 17.4% ± 3.3% per hour in the NaCl animals (p = 0.09). Interleukin 6 concentration 3 hours after the trauma was lower in the PGI2 animals than in the NaCl animals (p < 0.05). CONCLUSION: We conclude that PGI2 attenuates PV loss after blunt muscle trauma. The vascular effects of PGI2 are associated with a modulation of the trauma-induced inflammatory response.
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| 7. |
- Jungner, Mårten, et al.
(författare)
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Blood-brain barrier permeability following traumatic brain injury.
- 2016
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Ingår i: Minerva Anestesiologica. - 1827-1596. ; 82:5, s. 525-533
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Brain edema and intracranial hypertension is deleterious after traumatic brain injury (TBI), but the underlying pathophysiology is complex and poorly understood. One major subject of controversy is the time course and extent of blood-brain barrier (BBB) dysfunction following trauma, and previous studies in humans have only provided semi-quantitative data. The objective of the present study was therefore to quantify changes in BBB-permeability in the early course of TBI, when brain edema is still evolving. METHODS: Sixteen non-consecutive brain trauma patients and two controls were included. Following i.v. injection of iohexol and CT perfusion scans, patients were scanned eight times from 4 to 25 minutes. Blood to brain transfer constant (Ki) for iohexol (molecular weight 821 D), reflecting permeability and available area for diffusion, was calculated offline by Patlak plot analysis of the enhancement curves of intracerebral large venous vessels and pericontusional brain parenchyma. RESULTS : In non-ischemic tissue surrounding contusions and hematomas Ki was increased 2-to 10-fold compared to normal tissue, reaching maximal values of 0.5 mL/min/100 g. In non-injured areas and in controls Ki was about 0.06 mL/min/100 g. The increase was more pronounced in the most severely injured patients, and was detectable within 24 hours after trauma and up to five days after. CONCLUSIONS: Our results suggest that traumatic brain injury is associated with early focal increases in small molecular BBB-permeability. The results indicate that in the injured brain, capillary hydrostatic and oncotic pressures may influence edema formation.
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| 8. |
- Kamal, Nadia, et al.
(författare)
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The mosaic oat genome gives insights into a uniquely healthy cereal crop
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 606:7912, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- Cultivated oat (Avena sativa L.) is an allohexaploid (AACCDD, 2n = 6x = 42) thought to have been domesticated more than 3,000 years ago while growing as a weed in wheat, emmer and barley fields in Anatolia1,2. Oat has a low carbon footprint, substantial health benefits and the potential to replace animal-based food products. However, the lack of a fully annotated reference genome has hampered efforts to deconvolute its complex evolutionary history and functional gene dynamics. Here we present a high-quality reference genome of A. sativa and close relatives of its diploid (Avena longiglumis, AA, 2n = 14) and tetraploid (Avena insularis, CCDD, 2n = 4x = 28) progenitors. We reveal the mosaic structure of the oat genome, trace large-scale genomic reorganizations in the polyploidization history of oat and illustrate a breeding barrier associated with the genome architecture of oat. We showcase detailed analyses of gene families implicated in human health and nutrition, which adds to the evidence supporting oat safety in gluten-free diets, and we perform mapping-by-sequencing of an agronomic trait related to water-use efficiency. This resource for the Avena genus will help to leverage knowledge from other cereal genomes, improve understanding of basic oat biology and accelerate genomics-assisted breeding and reanalysis of quantitative trait studies.
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| 9. |
- Mohanty, Tirthankar, et al.
(författare)
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Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1667-1667
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications.
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| 10. |
- Adrian, Maria, et al.
(författare)
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Mechanical complications after central venous catheterisation in the ultrasound-guided era : a prospective multicentre cohort study
- 2022
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 129:6, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Limited data are available on the incidence of mechanical complications after ultrasound-guided central venous catheterisation. We aimed to determine the incidence of mechanical complications in hospitals where real-time ultrasound guidance is clinical practice for central venous access and to identify variables associated with mechanical complications.METHODS: All central venous catheter insertions in patients ≥16 yr at four emergency care hospitals in Sweden from March 2, 2019 to December 31, 2020 were eligible for inclusion. Every insertion was monitored for complete documentation and occurrence of mechanical complications within 24 h after catheterisation. Multivariable logistic regression analyses were used to determine associations between predefined variables and mechanical complications.RESULTS: In total, 12 667 catheter insertions in 8586 patients were included. The incidence (95% confidence interval [CI]) of mechanical complications was 7.7% (7.3-8.2%), of which 0.4% (0.3-0.5%) were major complications. The multivariable analyses showed that patient BMI <20 kg m -2 (odds ratio 2.69 [95% CI: 1.17-5.62]), male operator gender (3.33 [1.60-7.38]), limited operator experience (3.11 [1.64-5.77]), and increasing number of skin punctures (2.18 [1.59-2.88]) were associated with major mechanical complication. Subclavian vein catheterisation was associated with pneumothorax (5.91 [2.13-17.26]). CONCLUSIONS: The incidence of major mechanical complications is low in hospitals where real-time ultrasound guidance is the standard of care for central venous access. Several variables independently associated with mechanical complications can be used for risk stratification before catheterisation procedures, which might further reduce complication rates.CLINICAL TRIAL REGISTRATION: NCT03782324.
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| 11. |
- Adrian, Maria, et al.
(författare)
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Research protocol for mechanical complications after central venous catheterisation : a prospective controlled multicentre observational study to determine incidence and risk factors of mechanical complications within 24 hours after cannulation
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:10, s. 029301-029301
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Central venous catheterisation is a common procedure in intensive care therapy and the use of central venous catheters is essential for treatment of many medical disorders. Although rare, central venous catheterisation is associated with mechanical complications that can be life-threatening if untreated. Real-time ultrasound guidance reduces the incidence of mechanical complications when compared with the anatomic landmark method. The purpose of this study is to determine the incidence of and potential risk factors associated with early mechanical complications of central venous catheterisation in an era where real-time ultrasound guidance has become clinical practice. METHODS AND ANALYSIS: This is a prospective, controlled, multicentre, observational study. All participating hospitals follow the same clinical guidelines for central venous catheterisation. Each central venous catheter insertion will be recorded in the common electronic chart system according to a recently revised template. An automated script-based search will identify all recorded central venous catheter insertion templates during the study period and relevant variables will be extracted. Outcome measures and independent variables are pre-defined in this study protocol. Multivariable and univariable logistic regression analysis will be used to determine associations and risk factors of mechanical complications. ETHICS AND DISSEMINATION: The Regional Ethical Review Board in Lund, Sweden has approved this study. The results will be submitted for publication in peer-reviewed medical journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBER: NCT03782324.
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| 12. |
- Bentzer, Peter, et al.
(författare)
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Advances in Sepsis Research.
- 2015
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Ingår i: Clinics in Chest Medicine. - : Elsevier BV. - 1557-8216 .- 0272-5231. ; 36:3, s. 521-530
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Forskningsöversikt (refereegranskat)abstract
- Recent research has identified promising targets for therapeutic interventions aimed at modulating the inflammatory response in sepsis. Herein, the authors describe mechanisms involved in the clearance of pathogen toxin from the circulation and potential interventions aimed at enhancing clearance mechanisms. The authors also describe advances in the understanding of the innate immune response as potential therapeutic targets. Finally, novel potential treatment strategies aimed at decreasing vascular leak are discussed.
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| 13. |
- Bentzer, Peter, et al.
(författare)
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Capillary filtration coefficient is independent of number of perfused capillaries in cat skeletal muscle
- 2001
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Ingår i: American Journal of Physiology: Heart and Circulatory Physiology. - 1522-1539. ; 280:6, s. 2697-2706
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Tidskriftsartikel (refereegranskat)abstract
- The capillary filtration coefficient (CFC) is assumed to reflect both microvascular hydraulic conductivity and the number of perfused capillaries at a given moment (precapillary sphincter activity). Estimation of hydraulic conductivity in vivo with the CFC method has therefore been performed under conditions of unchanged vascular tone and metabolic influence. There are studies, however, that did not show any change in CFC after changes in vascular tone and metabolic influence, and these studies indicate that CFC may not be influenced by alteration in the number of perfused capillaries. The present study reexamined to what extent CFC in a pressure-controlled preparation depends on the vascular tone and number of perfused capillaries by analyzing how CFC is influenced by 1) vasoconstriction, 2) increase in metabolic influence by decrease in arterial blood pressure, and 3) occlusion of precapillary microvessels by arterial infusion of microspheres. CFC was calculated from the filtration rate induced by a fixed decrease in tissue pressure. Vascular tone was increased in two steps by norepinephrine (n = 7) or angiotensin II (n = 6), causing a blood flow reduction from 7.2 +/- 0.8 to at most 2.7 +/- 0.2 ml . min(-1) . 100 g(-1) (P< 0.05). The decrease in arterial pressure reduced blood flow from 4.8 +/- 0.4 to 1.40 +/- 0.1 ml . min(-1) . 100 g(-1) (n = 6). Vascular resistance increased to 990 +/- 260% of control after the infusion of microspheres (n = 6). CFC was not significantly altered from control after any of the experimental interventions. We conclude that CFC under these conditions is independent of the vascular tone and number of perfused capillaries and that variation in CFC reflects variation in microvascular hydraulic conductivity.
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| 14. |
- Bentzer, Peter, et al.
(författare)
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Effect of dextran-70 on outcome in severe sepsis; A propensity-score matching study
- 2017
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Albumin may be beneficial in patients with septic shock but availability is limited and cost is high. The objective of the present study was to investigate if the use of dextran-70 in addition to albumin and crystalloids influences organ failure or mortality in patients with severe sepsis or septic shock. Methods: Patients with severe sepsis or septic shock (n = 778) admitted to a university hospital intensive care unit (ICU) between 2007 and 2015 that received dextran-70 during resuscitation were propensity score matched to controls at a 1 to 1 ratio. Outcomes were highest acute kidney injury network (AKIN) score the first 10 days in the ICU, use of renal replacement therapy, days alive and free of organ support the first 28 days after admission to ICU, mortality and events of severe bleeding. Outcomes were assessed using paired hypothesis testing. Results: Propensity score matching resulted in two groups of patients with 245 patients in each group. The dextran group received a median volume of 1483 ml (interquartile range, 1000-2000 ml) of dextran-70 during the ICU stay. Highest AKIN score did not differ between the control- and dextran groups (1 (0-3) versus 2 (0-3), p = 0.06). Incidence of renal replacement therapy in the control- and dextran groups was similar (19% versus 22%, p = 0.42, absolute risk reduction -2.9% [95% CI: -9.9 to 4.2]). Days alive and free of renal replacement, vasopressors and mechanical ventilation did not differ between the control- and dextran groups. The 180-day mortality was 50.2% in the control group and 41.6% in the dextran group (p = 0.046, absolute risk reduction 8.6% [-0.2 to 17.4]). Fraction of patients experiencing a severe bleeding in the first 10 days in the ICU did not differ between the control and dextran groups (14% versus 18%, p = 0.21). Discussion: There is a paucity of high quality data regarding effects of dextran solutions on outcome in sepsis. In the present study, propensity score matching was used in attempt to reduce bias. Conclusion: No evidence to support a detrimental effect of dextran-70 on mortality or on organ failures in patients with severe sepsis or septic shock could be detected.
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| 15. |
- Bentzer, Peter, et al.
(författare)
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Endothelin-1 Reduces Microvascular Fluid Permeability through Secondary Release of Prostacyclin in Cat Skeletal Muscle.
- 2002
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 63:1, s. 50-60
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to analyze effects of various plasma concentrations of the vasoconstrictor endothelin-1 on microvascular fluid permeability and on transcapillary fluid exchange. We also analyzed whether the permeability-reducing substance prostacyclin is involved in the permeability effects of endothelin-1, as prostacylin is suggested to be released via ET(B) receptor stimulation. The study was performed on an autoperfused cat calf muscle preparation, and a capillary filtration coefficient (CFC) technique was used to estimate variations in microvascular fluid permeability (conductivity). Intraarterial infusion of endothelin-1 in low doses (5 and 10 ng/min/100 g muscle) caused transcapillary absorption, whereas higher doses (20-40 ng/min/100 g) induced filtration despite further vasoconstriction. Low-dose endothelin-1 had no significant effect on CFC, while CFC was reduced to at most 55% of baseline at higher doses (P < 0.01). Simultaneous local intraarterial infusion of the prostacyclin synthesis inhibitor tranylcypromine restored CFC to 114% of baseline (P < 0.01) and further increased vascular resistance. A low, nonvasodilator dose of prostacyclin given intravenously counteracted the tranylcypromine effect on CFC. The decreased CFC induced by a high dose of endothelin-1 was counteracted by the ET(B) receptor antagonist BQ-788 with no change in vascular resistance (P < 0.05). We conclude that the decreased CFC following high doses of endothelin-1 can be attributed to a decrease in microvascular hydraulic conductivity, mediated by secondary release of prostacylin via stimulation of the ET(B) receptor. Endothelin-1 may induce edema through postcapillary vasoconstriction. (c)2001 Elsevier Science.
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| 16. |
- Bentzer, Peter, et al.
(författare)
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Evaluation of capillary perfusion - Reply
- 2002
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Ingår i: American Journal of Physiology: Heart and Circulatory Physiology. - 1522-1539. ; 282:3, s. 1172-1173
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 17. |
- Bentzer, Peter, et al.
(författare)
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Heparin-binding protein is important for vascular leak in sepsis
- 2016
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Elevated plasma levels of heparin-binding protein (HBP) are associated with risk of organ dysfunction and mortality in sepsis, but little is known about causality and mechanisms of action of HBP. The objective of the present study was to test the hypothesis that HBP is a key mediator of the increased endothelial permeability observed in sepsis and to test potential treatments that inhibit HBP-induced increases in permeability.METHODS: Association between HBP at admission with clinical signs of increased permeability was investigated in 341 patients with septic shock. Mechanisms of action and potential treatment strategies were investigated in cultured human endothelial cells and in mice.RESULTS: Following adjustment for comorbidities and Acute Physiology and Chronic Health Evaluation (APACHE) II, plasma HBP concentrations were weakly associated with fluid overload during the first 4 days of septic shock and the degree of hypoxemia (PaO2/FiO2) as measures of increased systemic and lung permeability, respectively. In mice, intravenous injection of recombinant human HBP induced a lung injury similar to that observed after lipopolysaccharide injection. HBP increased permeability of vascular endothelial cell monolayers in vitro, and enzymatic removal of luminal cell surface glycosaminoglycans (GAGs) using heparinase III and chondroitinase ABC abolished this effect. Similarly, unfractionated heparins and low molecular weight heparins counteracted permeability increased by HBP in vitro. Intracellular, selective inhibition of protein kinase C (PKC) and Rho-kinase pathways reversed HBP-mediated permeability effects.CONCLUSIONS: HBP is a potential mediator of sepsis-induced acute lung injury through enhanced endothelial permeability. HBP increases permeability through an interaction with luminal GAGs and activation of the PKC and Rho-kinase pathways. Heparins are potential inhibitors of HBP-induced increases in permeability.
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| 18. |
- Bentzer, Peter, et al.
(författare)
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Infusion of prostacyclin following experimental brain injury in the rat reduces cortical lesion volume
- 2001
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 18:3, s. 275-285
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial-derived prostacyclin is an important regulator of microvascular function, and its main actions are inhibition of platelet/leukocyte aggregation and adhesion, and vasodilation. Disturbances in endothelial integrity following traumatic brain injury (TBI) may result in insufficient prostacyclin production and participate in the pathophysiological sequelae of brain injury. The objective of this study was to evaluate the potential therapeutic effects of a low-dose prostacyclin infusion on cortical lesion volume, CA3 neuron survival and functional outcome following TBI in the rat. Anesthetized animals (sodium pentobarbital, 60 mg/kg, i.p.) were subjected to a lateral fluid percussion brain injury (2.5 atm) or sham injury. Following TBI, animals were randomized to receive a constant infusion of either prostacyclin (1 ng/kg x min(-1) i.v.) or vehicle over 48 h. All sham animals received vehicle (n = 6). Evaluation of neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly. By 7 days postinjury, cortical lesion volume was significantly reduced by 43% in the prostacyclin-treated group as compared to the vehicle treated group (p < 0.01; n = 12 prostacyclin, n = 12 vehicle). No differences were observed in neuromotor function (48 h and 7 days following TBI), or in hippocampal cell loss (7 days following TBI) between the prostacyclin- and vehicle-treated groups. We conclude that prostacyclin in a low dose reduces loss of neocortical neurons following TBI and may be a potential clinical therapeutic agent to reduce neuronal cell death associated with brain trauma.
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| 19. |
- Bentzer, Peter, et al.
(författare)
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Isolated Brain Trauma in Cats Triggers Rapid Onset of Hypovolemia
- 2017
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Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 26:3, s. 450-456
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hemodynamic instability responsive to fluid resuscitation is common after a traumatic brain injury (TBI), also in the absence of systemic hemorrhage. The present study tests if an isolated severe TBI induces a decrease in plasma volume (PV). Methods: The study was performed in three groups of anesthetized and tracheostomized male cats (n = 21). In one group (n = 8), the cats were prepared with a cranial borehole (10 mm i.d) used to expose the brain to a fluid percussion brain injury (FPI) (1.90–2.20 bar), and two smaller cranial boreholes (4 mm i.d) for insertion of an intracranial pressure (ICP) and a microdialysis catheter. To differentiate the effect of FPI from that of the surgical preparation, a sham group was exposed to the same surgical preparation but no FPI trauma (n = 8). A control group had no brain trauma and no surgical preparation (n = 5). PV was determined by a 125I-albumin dilution technique. PV, electrolytes, pH, BE (base excess), hematocrit (Hct), PaO2, and PaCO2 were measured at baseline and after 3 h. Mean arterial pressure (MAP) was measured continuously. ICP was measured in the FPI and the sham group. Results: In the FPI group, PV decreased by 11.2 mL/kg from 31.7 mL/kg (p < 0.01) with a simultaneous increase in Hct and decrease in pH. In the sham group, PV decreased by 5.7 mL/kg from 32.7 mL/kg (p < 0.01). The control group showed no PV reduction. Conclusions: The results support that an isolated severe head trauma triggers a significant and rapid reduction in PV, most likely due to vascular leak.
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| 20. |
- Bentzer, Peter, et al.
(författare)
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Low-Dose Prostacyclin Improves Cortical Perfusion following Experimental Brain Injury in the Rat.
- 2003
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 20:5, s. 447-461
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Tidskriftsartikel (refereegranskat)abstract
- It was recently shown that prostacyclin at a low dose reduces cortical cell death following brain trauma in the rat. Conceivably, prostacyclin with its vasodilatory, anti-aggregatory, anti-adhesive and permeability-reducing properties improved a compromised perfusion caused by post-traumatic vasoconstriction, microthrombosis and increased microvascular permeability. The objective of the present study was therefore to investigate the hemodynamic effects of low-dose prostacyclin in the traumatized rat cortex. Following a fluid percussion brain injury or a sham procedure, animals were treated with a continuous intravenous infusion of prostacyclin of 1 or 2 ng x kg(-1) x min(-1), or vehicle. Blood flow ([(14)C]-iodoantipyrine), the permeability-surface area product (PS) for [(51)Cr]-EDTA, and brain water content were measured after 3 or 48 h of treatment. Blood flow values in the injured cortex were transiently reduced to 0.42 +/- 0.2 mL x min(-1) in the vehicle group 3 h following trauma from a corresponding value of about 1.6 mL x min(-1) in the sham group, with recovery of blood flow after 48 h. Prostacyclin treatment caused a dose-dependent increase in blood flow which reached statistical significance 48 h following trauma. Brain water content and PS increased in the injured cortex post trauma and the higher dose of prostacyclin increased these parameters further at 48 h compared to the vehicle group (p < 0.05). The latter effects of prostacyclin cannot be attributed to an increase in permeability, as prostacyclin did not influence PS or brain water content following sham trauma. In fact prostacyclin has been shown to have permeability-decreasing properties. We conclude that prostacyclin improves cortical perfusion following brain trauma. The simultaneous aggravation of brain edema can be explained by an increased surface area, perhaps in combination with increased capillary hydrostatic pressure.
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| 21. |
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| 22. |
- Bentzer, Peter, et al.
(författare)
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Microdialysis-based long-term measurements of energy-related metabolites in the rat brain following a fluid percussion trauma
- 2000
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Ingår i: Journal of Neurotrauma. - 1557-9042. ; 17:5, s. 441-447
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate an experimental approach based on a fluid percussion rat trauma model in combination with the microdialysis technique for the analysis of cerebral interstitial biochemical alterations following head trauma, and to test the hypothesis that the previously observed acute accumulation of lactate and increase in the lactate pyruvate ratio may persist for several days following trauma. We analyzed how lactate, pyruvate, and glucose were altered in the cortex adjacent to the contusion and in the contralateral side of the brain following a traumatic brain injury. The results were compared with those from sham-operated animals. The lactate concentration in the cortex adjacent to the contusion was 0.73 +/- 0.13 mmol/L and 0.71 +/- 0.08 mmol/L 24 and 48 h posttrauma, respectively, and 0.42 +/- 0.07 mmol/L in the sham group (p < 0.05). The lactate/pyruvate ratio of 18.3 +/- 2.3 in the cortex adjacent to the contusion 24 h posttrauma was higher than corresponding value of 10.3 +/- 1.5 in the sham group (p < 0.05). The lactate/pyruvate ratio 48 h posttrauma did not differ from that in the sham group. Interstitial glucose in the cortex adjacent to the contusion and the sham group were similar. Microdialysis measurements from the contralateral side did not differ from those in the sham group. We conclude that the previously observed acute alterations in brain metabolism persist for at least 48 h posttrauma. Further, the measured parameters from the contralateral side can be used as controls since they did not differ from the sham group. Combining microdialysis with a fluid percussion trauma model may be a tool to explore secondary brain injury mechanisms and evaluate new therapies for the treatment of traumatic brain injury.
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| 23. |
- Bentzer, Peter, et al.
(författare)
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Plasma cytokine levels predict response to corticosteroids in septic shock
- 2016
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 42:12, s. 1970-1979
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate if plasma cytokine concentrations predict a beneficial response to corticosteroid treatment in septic shock patients. Methods: A cohort of septic shock patients in whom a panel of 39 cytokines had been measured at baseline (n = 363) was included. Patients who received corticosteroids were propensity score matched to non-corticosteroid-treated patients. An optimal threshold to identify responders to corticosteroid treatment for each cytokine was defined as the concentration above which the odds ratio for 28-day survival between corticosteroid- and non-corticosteroid-treated patients was highest. Results: Propensity score matching partitioned 165 patients into 61 sets; each set contained matched corticosteroid- and non-corticosteroid-treated patients. For 13 plasma cytokines threshold concentrations were found where the odds ratio for survival between corticosteroid- and non-corticosteroid-treated patients was significant (P <0.05). CD40 ligand was associated with the highest odds ratio and identified 21 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. Combinations of triplets of cytokines with a significant odds ratio, using the thresholds identified above, were tested to find a higher proportion of responders. IL3, IL6, and CCL4 identified 50 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. The odds ratio for 28-day survival was 19 (95 % CI 3.5–140, P = 0.02) with a concentration above threshold for a least one of these cytokines. Conclusion: Plasma concentration of selected cytokines is a potential predictive biomarker to identify septic shock patients that may benefit from treatment with corticosteroids.
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| 24. |
- Bentzer, Peter, et al.
(författare)
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Prostacyclin reduces microvascular fluid conductivity in cat skeletal muscle through opening of ATP-dependent potassium channels
- 1999
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Ingår i: Journal of Vascular Research. - 1423-0135. ; 36:6, s. 516-523
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Tidskriftsartikel (refereegranskat)abstract
- Prostacyclin is suggested to reduce microvascular permeability, but the cellular mechanisms mediating this response in the microvascular endothelial cells are still unknown. Considering that prostacyclin relaxes vascular smooth muscle cells via opening of ATP-dependent potassium channels, and opening of ATP-dependent potassium channels in the endothelial cells is suggested to influence microvascular permeability, this study was designed to test (1) if ATP-dependent potassium channels are involved in the regulation of microvascular hydraulic permeability, (2) if the permeability-reducing effect of prostacyclin is mediated through opening of ATP-dependent potassium channels, and (3) if cAMP is involved in this process. An autoperfused cat calf hindlimb was used as experimental model, and microvascular hydraulic permeability (conductivity) was estimated by a capillary filtration coefficient (CFC) technique. The potassium channel opener PCO-400 (0.5 microg x min(-1) per 100 g muscle, intra-arterially), prostacyclin (1 ng x min(-1) per kg body weight, intravenously) and the cAMP analogue dibutyryl-cAMP (24 microg x min(-1) per 100 g muscle, intra-arterially), decreased CFC to 77, 72 and 69% compared to control, respectively (p < 0.01). The decrease in CFC obtained by these substances was completely restituted after the start of a simultaneous infusion of the ATP-dependent potassium channel blocker glibenclamide (6 microg x min(-1) per 100 g muscle, intra-arterially; p < 0.01). Infusion of glibenclamide alone increased CFC to 107% of control (p < 0.05). In conclusion, the ATP-dependent potassium channels contribute to the regulation of microvascular hydraulic conductivity, and the prostacyclin permeability-reducing effect may act through this mechanism via increase in intracellular cAMP.
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| 25. |
- Bentzer, Peter, et al.
(författare)
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Supersensitivity in rat micro-arteries after short-term denervation
- 1997
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 161:2, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- Contractile responses to phenylephrine and high-K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short-term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 microns) were obtained 10 days after surgery. Vessels from the non-operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high-K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short-term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic alpha-receptors but also associated with changes in the cellular excitation-contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.
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