| 1. |
- Holm, Anders, et al.
(författare)
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The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner.
- 2012
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Ingår i: Molecular and Cellular Biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 366:1-2, s. 239-249
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Tidskriftsartikel (refereegranskat)abstract
- The G protein-coupled oestrogen receptor GPER1, also known as GPR30, has been implicated in oestrogen signalling, but the physiological importance of GPER1 is not fully understood. The GPER1 agonist G-1 has become an important tool to assess GPER1-mediated cellular effects. Here, we report that this substance, besides acting via GPER1, affects the microtubule network in endothelial cells. Treatment with G-1 (3 μM) for 24 h reduced DNA synthesis by about 60 % in mouse microvascular endothelial bEnd.3 cells. Treatment with 3 μM G-1 prevented outgrowth of primary endothelial cells from mouse aortic explants embedded in Matrigel. Treatment with G-1 (0.3-3 μM) for 24 h disrupted bEnd.3 cell and HUVEC microtubule structure in a concentration-dependent manner as assessed by laser-scanning confocal immunofluorescence microscopy. G-1-induced (3 μM) disruption of microtubule was observed also after acute (3 and 6 h) treatment and in the presence of the protein synthesis inhibitor cycloheximide. Disruption of microtubules by 3 μM G-1 was observed in aortic smooth muscle cells obtained from both GPER1 knockout and wild-type mice, suggesting that G-1 influences microtubules through a mechanism independent of GPER1. G-1 dose dependently (10-50 μM) stimulated microtubule assembly in vitro. On the other hand, microtubules appeared normal in the presence of 10-50 μM G-1 as determined by electron microscopy. We suggest that G-1-promoted endothelial cell anti-proliferation is due in part to alteration of microtubule organization through a mechanism independent of GPER1. This G-1-promoted mechanism may be used to block unwanted endothelial cell proliferation and angiogenesis such as that observed in, e.g. cancer.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- Bark, Björn, et al.
(författare)
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Importance of the Infusion Rate for the Plasma Expanding Effect of 5% Albumin, 6% HES 130/0.4, 4% Gelatin, and 0.9% NaCl in the Septic Rat.
- 2013
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Ingår i: Critical Care Medicine. - 1530-0293. ; 41:3, s. 857-866
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:: To compare the plasma volume (PV) expanding effect of a fast infusion rate with that of a slow infusion rate of a fixed volume of 5% albumin, of the synthetic colloids, 6% hydroxyethyl starch 130/0.4 and 4% gelatin, and of 0.9% NaCl in a rat sepsis model and to compare the plasma-expanding effect among these fluids. DESIGN:: Prospective, randomized animal study. SETTING:: University hospital laboratory. SUBJECTS:: One hundred and twelve adult male rats. INTERVENTIONS:: Sepsis was induced by cecal ligation and incision followed by closure of the abdomen. After 3 hrs, an infusion of the PV expander under study was started at a volume of 12 mL/kg for the colloids and of 48 mL/kg for 0.9% NaCl, either for 15 mins or for 3 hrs. A control group underwent the same experimental procedure but no fluid was given. MEASUREMENTS AND MAIN RESULTS:: Three hours after start of the infusion (end of experiment), the plasma-expanding effect was better with a slow than a fast infusion rate for the colloids, especially albumin, but the NaCl groups did not differ significantly from the control group. The PV for the control group was 28.7 ± 3 mL/kg. In the slow and the fast infusion groups, it was 38.9 ± 4.3 and 32.6 ± 4.2 mL/kg for albumin (p < 0.001), 32.9 ± 4.3 and 29.5 ± 4.4 mL/kg for hydroxyethyl starch 130/0.4 (p < 0.05), 31.8 ± 3.9 and 28.2 ± 4.1 mL/kg for gelatin (p < 0.05), and 31.8 ± 5.3 and 30.7 ± 6.6 mL/kg for NaCl (n.s), respectively. CONCLUSIONS:: The study showed that the PV expansion by a colloid was greater when given at a slow than at a fast infusion rate, an effect more pronounced for albumin. This difference was not seen for NaCl. The PV-expanding effect was poor for NaCl and better for albumin than for the other colloids.
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| 5. |
- Bark, Björn, et al.
(författare)
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Infusion rate and plasma volume expansion of dextran and albumin in the septic guinea pig.
- 2014
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 58:1, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- Intravenous fluid treatment of hypovolaemia in states of increased capillary permeability, e.g. sepsis, is often accompanied by adverse oedema formation. A challenge is therefore to achieve and maintain normovolaemia using as little plasma volume substitution as possible to minimise interstitial oedema. In the present study, we evaluated the importance of infusion rate for the plasma volume expanding effects of 6% dextran 70 and 5% human albumin in a guinea pig sepsis model.
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| 6. |
- Bark, Björn, et al.
(författare)
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Plasma Volume Expansion by 0.9% NaCl During sepsis/SIRS, After Hemorrhage, and During a Normal State.
- 2013
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Ingår i: Shock. - 1540-0514. ; 40:1, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the degree of plasma volume expansion by 0.9% NaCl in relation to the infused volume, in sepsis/SIRS (systemic inflammatory response syndrome), after a standardized hemorrhage, and in a normal condition. DESIGN: Prospective, randomized animal study. SETTING: University hospital laboratory. SUBJECTS: Thirty anesthetized adult male rats. INTERVENTIONS: The study was performed in 3 groups: a sepsis/SIRS group (the S group), in which sepsis/SIRS was induced by cecal ligation and incision, a hemorrhage group (the H group), in which the rats were left without intervention for 4 hrs, and bled 8 mL/kg thereafter. The study also included a group that was left without intervention (the N group). Then, 4 hrs after baseline, all 3 groups were given an infusion of 0.9% NaCl (32 mL/kg) for 15 mins. Baseline was defined as the time point when the surgical preparation was finished. MEASUREMENTS AND MAIN RESULTS: Plasma volumes were measured using I-albumin dilution technique at baseline, after 4 hrs, and 20 mins after the end of infusion. The plasma volume-expanding effect 20 mins after end of infusion was 0.6 ± 2.9% in the S group, 20 ± 6.4% in the H group and 12 ± 11% in the N group, compared to just before start of infusion. CONCLUSIONS: The present study in rats showed that the plasma volume-expanding effect after an infusion of 0.9% NaCl was smaller in a septic/SIRS state than after hemorrhage and in a normal state. This indicates that the plasma volume expanding effect of a crystalloid in sepsis/SIRS is dependent on pathophysiological changes.
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| 7. |
- Bark, Björn, et al.
(författare)
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The effect of vitamin C on plasma volume in the early stage of sepsis in the rat.
- 2014
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Ingår i: Intensive Care Medicine Experimental. - 2197-425X. ; 2:11
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Tidskriftsartikel (refereegranskat)abstract
- Previous experimental studies have shown that vitamin C has several beneficial effects in sepsis and burns, such as decreased tissue oedema, improved endothelial barrier function and decreased transcapillary leakage of plasma markers. It has still not been investigated, though, if vitamin C has any impact specifically on plasma volume. The present study aims at testing the hypothesis that vitamin C decreases plasma volume loss in sepsis.
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| 8. |
- Grände, Per-Olof, et al.
(författare)
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Aktivt induceret hypotermi efter svaer traumatisk hjerneskade.
- 2010
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Ingår i: Ugeskrift for Læger. - 0041-5782. ; 172:19, s. 1437-1440
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Tidskriftsartikel (refereegranskat)abstract
- A Cochrane metaanalysis and a study performed on children have recently confirmed that therapeutic hypothermia does not improve outcome after severe traumatic brain injury (TBI). TBI is not comparable to a short episode of global ischemia, where therapeutic hypothermia has been shown to improve outcome. The difference may be explained by the fact that hypothermia-induced stress after a traumatic brain injury reduces cerebral perfusion in the penumbra zone, where local circulation is already reduced. Thus, to date there is no indication for therapeutic hypothermia in TBI patients.
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| 9. |
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| 10. |
- Grände, Per-Olof, et al.
(författare)
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Osmotherapy in brain edema: a questionable therapy.
- 2012
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Ingår i: Journal of Neurosurgical Anesthesiology. - : Ovid Technologies (Wolters Kluwer Health). - 1537-1921 .- 0898-4921. ; 24:4, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- Despite the fact that it has been used since the 1960s in diseases associated with brain edema and has been investigated in >150 publications on head injury, very little has been published on the outcome of osmotherapy. We can only speculate whether osmotherapy improves outcome, has no effect on outcome, or leads to worse outcome. Here we describe the action and potentially beneficial and adverse effects of the 2 most commonly used osmotic solutions, mannitol and hypertonic saline, and present some critical aspects of their use. There is a well-documented transient intracranial pressure (ICP)-reducing effect of osmotherapy, but an adverse rebound increase in ICP after its withdrawal has been discussed extensively in the literature and is an expected pathophysiological phenomenon. From side effects related to renal and pulmonary failure, electrolyte disturbances, and a rebound increase in ICP, osmotherapy can be negative for outcome, which may explain why we lack scientific support for its use. These drawbacks, and the fact that the most recent Cochrane meta-analyses of osmotherapy in brain edema and stroke could not find any beneficial effects on outcome, make routine use of osmotherapy in brain edema doubtful. Nevertheless, the use of osmotherapy as a temporary measure may be justified to acutely prevent brain stem compression until other measures, such as evacuation of space-occupying lesions or decompressive craniotomy, can be performed. This article is the Con part in a Pro-Con debate in the present journal on the general routine use of osmotherapy in brain edema.
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| 11. |
- Grände, Per-Olof
(författare)
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PRO: The "Lund Concept" for Treatment of Patients With Severe Traumatic Brain Injury.
- 2011
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Ingår i: Journal of Neurosurgical Anesthesiology. - 1537-1921. ; 23, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- Two different main concepts for the treatment of severe traumatic brain injury have been established during the last 15 years, namely the more conventional concept recommended in well-established guidelines (eg, the US Guideline, European Guideline, Addelbrook's Guideline from Cambridge) on the one hand, and the Lund concept from the University Hospital of Lund, Sweden on the other. Owing to the lack of well-controlled randomized outcome studies comparing these 2 main therapeutic approaches, we cannot conclude that one is better than the other. This study is the PRO part in a PRO-CON debate on the Lund concept in the present journal. Although the Lund concept is based on a physiology-oriented approach dealing with hemodynamic principles of brain volume and brain perfusion regulation, traditional treatments are primarily based on a meta-analytic approach from clinical studies. High cerebral perfusion pressure has been an essential goal in the conventional treatments (the cerebral perfusion pressure-guided approach), even though it has been modified in a recent update of US guidelines. The Lund concept has instead concentrated on management of brain edema and intracranial pressure, simultaneously with improvement of cerebral perfusion and oxygenation (the intracranial pressure and perfusion-guided approach). Although conventional guidelines are restricted to clinical data from meta-analytic surveys, the physiological approach of the Lund therapy finds support in both experimental and clinical studies. It offers a wider base and can also give recommendations regarding fluid therapy, lung protection, optimal hemoglobin concentration, temperature control, the use of decompressive craniotomy, and ventricular drainage. This study puts forward arguments in support of the Lund therapy.
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| 12. |
- Grände, Per-Olof, et al.
(författare)
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Segmental cerebral vasoconstriction: successful treatment of secondary cerebral ischaemia with intravenous prostacyclin.
- 2010
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 30:7, s. 890-895
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Tidskriftsartikel (refereegranskat)abstract
- We describe a 23-year-old male patient who presented with spontaneous intermittent and increasing attacks of severe, left-sided thunderclap headache combined with rapidly progressive muscle weakness and dysphasia, including gradual loss of consciousness. Subsequent CT, MRI and DSA showed progressive brain ischaemia and oedema within the left cerebral hemisphere with strict ipsilateral segmental arterial vasoconstriction. Despite extensive medical care, including steroids, the patient deteriorated rapidly. However, the clinical course changed dramatically within 15 h after the start of an intravenous infusion of prostacyclin at a dose of 0.9 ng/kg/min, with an almost complete recovery of consciousness and speech. In addition the pathophysiological alterations seen on magnetic resonance (imaging and digital) subtraction angiography including diffusion-weighted imaging and apparent diffusion coefficient maps shortly before prostacyclin treatment were clearly reduced when the patient was examined 3-4 days later and he continued to recover thereafter. Although not fully compatible, our case had several clinical characteristics and radiological findings reminiscent of those of the 'segmental reversible vasoconstriction syndrome', sometimes called the Call-Fleming syndrome.
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| 13. |
- Grände, Per-Olof
(författare)
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The lund concept for the treatment of patients with severe traumatic brain injury.
- 2011
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Ingår i: Journal of Neurosurgical Anesthesiology. - : Ovid Technologies (Wolters Kluwer Health). - 1537-1921 .- 0898-4921. ; 23:4, s. 358-362
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Tidskriftsartikel (refereegranskat)abstract
- Two different main concepts for the treatment of a severe traumatic brain injury have been established during the last 15 years, namely the more conventional concept recommended in well-established guidelines (eg, U.S. Guideline, European Guideline, Addelbrook's Guideline from Cambridge), on the one hand, and the Lund concept from the University Hospital of Lund, Sweden, on the other. Owing to the lack of well-controlled randomized outcome studies comparing these 2 main therapeutic approaches, we cannot conclude that one is better than the other. This paper is the PRO part in a PRO-CON debate in this journal on the Lund concept. Although the Lund concept is based on a physiology-oriented approach dealing with the hemodynamic principles of brain volume and brain perfusion regulation, traditional treatments are primarily based on a meta-analytic approach from clinical studies. High cerebral perfusion pressure has been an essential goal in the conventional treatments (the cerebral perfusion pressure-guided approach), even though it has been modified in a recent up date of U.S. guidelines. The Lund concept has instead concentrated on management of brain edema and intracranial pressure, along with improvement of cerebral perfusion and oxygenation (the intracranial pressure and perfusion-guided approach). Although conventional guidelines are restricted to clinical data from meta-analytic surveys, the physiological approach of Lund therapy finds support in both experimental and clinical studies. It offers a wider base and can also provide recommendations regarding fluid therapy, lung protection, optimal hemoglobin concentration, temperature control, the use of decompressive craniotomy, and ventricular drainage. This paper puts forward arguments in support of Lund therapy.
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| 14. |
- Jungner, Mårten, et al.
(författare)
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Effects on brain edema of crystalloid and albumin fluid resuscitation after brain trauma and hemorrhage in the rat.
- 2010
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Ingår i: Anesthesiology. - 1528-1175. ; 112:5, s. 1194-1203
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has been hypothesized that resuscitation with crystalloids after brain trauma increases brain edema compared with colloids, but previous studies on the subject have been inconclusive. To test this hypothesis, the authors compared groups resuscitated with either colloid or crystalloid. METHODS: After fluid percussion injury, rats were subjected to a controlled hemorrhage of 20 ml/kg and were randomized to 5% albumin at 20 ml/kg (A20), isotonic Ringer's acetate at 50 ml/kg (C50), or 90 ml/kg (C90). After 3 or 24 h, water content in the injured cortex was determined using a wet/dry weight method. Blood volume was calculated from plasma volume, measured by 125I-albumin dilution, and hematocrit. Oncotic pressure and osmolality were measured with osmometers. RESULTS: At 3 h, blood volume was equal in the A20 and C90 groups and lower in the C50 group. Oncotic pressure was reduced by 35-40% in the crystalloid groups and unchanged in the albumin group. Cortical water content in the A20 group was lower than in the C90 group (81.3 +/- 0.5% vs. 82.1 +/- 1.1%, P < 0.05), but it was not different from the C50 group (81.8 +/- 1.1%). At 24 h, oncotic pressure and blood volume were normalized in all groups, and cortical water content was significantly lower in the albumin group than in the crystalloid groups. Osmolality and arterial pressure were equal in all groups throughout the experiment. CONCLUSIONS: When given to the same intravascular volume expansion, isotonic crystalloids caused greater posttraumatic brain edema than 5% albumin at 3 and 24 h after trauma.
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| 15. |
- Jungner, Mårten, et al.
(författare)
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Intracranial pressure following resuscitation with albumin or saline in a cat model of meningitis.
- 2011
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Ingår i: Critical Care Medicine. - 1530-0293. ; Dec, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: To compare the intracranial pressure after resuscitation to normovolemia by using 20% albumin or normal saline in a cat model of meningitis. DESIGN:: Prospective, randomized animal study. SETTING:: University hospital laboratory. SUBJECTS:: Twenty adult, male cats. INTERVENTIONS:: Meningitis was induced by intrathecal injection of Escherichia coli-derived lipopolysaccharide (0.8 × 10 units/kg). Four hours after the lipopolysaccharide injection, the animals were randomized to intravenous treatment with 0.4 mL/kg/hr of 20% albumin or 7.5 mL/kg/hr of 0.9% sodium chloride for 6 hrs (n = 7 per group). A control group receiving lipopolysaccharide but no fluid was also studied (n = 6). MEASUREMENTS AND MAIN RESULTS:: Effects on intracranial pressure, mean arterial pressure, plasma volume (I-albumin technique), plasma oncotic pressure, and brain metabolism via cerebral interstitial lactate/pyruvate ratio and glycerol and glucose levels (microdialysis technique) were evaluated. Plasma volume decreased by approximately 20% and intracranial pressure increased from 10 to approximately 20 mm Hg at 4 hrs after the lipopolysaccharide injection. Six hours later, plasma volume had returned to baseline in both fluid groups while there was a further reduction in the control group. Intracranial pressure was higher in the saline group than in the albumin and control groups and was 25.8 ± 2.8 mm Hg, 18.3 ± 0.6 mm Hg, and 20.4 ± 1.7 mm Hg, respectively. Plasma oncotic pressure was higher in the albumin group than in the saline and control groups. Mean arterial pressure and microdialysis data were within normal range and did not differ among the groups. CONCLUSIONS:: The results showed that the choice of resuscitation fluid may influence intracranial pressure in meningitis. The lower intracranial pressure in the colloid group may be explained by a higher plasma oncotic pressure and less fluid distribution to the brain interstitium.
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| 16. |
- Koskinen, Lars-Owe, et al.
(författare)
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Severe traumatic brain injury management and clinical outcome using the Lund concept
- 2014
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 283, s. 245-255
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Forskningsöversikt (refereegranskat)abstract
- This review covers the main principles of the Lund concept for treatment of severe traumatic brain injury. This is followed by a description of results of clinical studies in which this therapy or a modified version of the therapy has been used. Unlike other guidelines, which are based on meta-analytical approaches, important components of the Lund concept are based on physiological mechanisms for regulation of brain volume and brain perfusion and to reduce transcapillary plasma leakage and the need for plasma volume expanders. There have been nine non-randomized and two randomized outcome studies with the Lund concept or modified versions of the concept. The non-randomized studies indicated that the Lund concept is beneficial for outcome. The two randomized studies were small but showed better outcome in the groups of patients treated according to the modified principles of the Lund concept than in the groups given a more conventional treatment. This article is part of a Special Issue entitled: Brain compensation. For good?. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
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| 17. |
- Lundblad, Cornelia, et al.
(författare)
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Treatment with the sphingosine-1-phosphate analogue FTY 720 reduces loss of plasma volume during experimental sepsis in the rat.
- 2013
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 57:6, s. 713-718
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased vascular leakage leading to hypovolaemia and tissue oedema is common in severe sepsis. Hypovolaemia together with oedema formation may contribute to hypoxia and result in multiorgan failure and death. To improve treatment during sepsis, a potential therapeutic target may be to reduce the vascular leakage. Substances affecting the endothelial barrier are interesting in this respect, as it is suggested that increase in vascular leakage depends on reorganisation of the endothelial cells and breakdown of the endothelial barrier. The agonist of the bioactive lipid sphingosine-1-phosphate, FTY720, has been shown to modulate the integrity of the endothelium and reduce permeability both in vitro and in vivo. The aim of the present study was to determine if FTY720 could reduce the loss of plasma volume during experimental sepsis in rats. METHODS: Sepsis was induced by ligation and incision of the caecum in the rat. Plasma volume was determined before and 4.5 h after induction of sepsis by a dilution technique using (125) I-labelled albumin. RESULTS: FTY720 in a dose of 0.2 mg/kg reduced the loss of plasma during sepsis by approximately 30% compared with vehicle, without any adverse effects on haemodynamic and physiological parameters. The increase in hematocrit and haemoglobin concentration was also found to be higher in the vehicle group. CONCLUSION: FTY720 in a dose without haemodynamic side effects reduces loss of plasma volume during experimental sepsis most likely because of reduction in permeability and may therefore be beneficial in sepsis.
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| 18. |
- Rasmussen, Rune, et al.
(författare)
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The effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage: study protocol for a randomised controlled trial
- 2012
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the main causes of mortality and morbidity following subarachnoid haemorrhage (SAH) is the development of cerebral vasospasm, a frequent complication arising in the weeks after the initial bleeding. Despite extensive research, to date no effective treatment of vasospasm exists. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. In vitro models have shown a relaxing effect of prostacyclin after induced contraction in cerebral arteries, and a recent pilot trial showed a positive effect on cerebral vasospasm in a clinical setting. No randomised, clinical trials have been conducted, investigating the possible pharmacodynamic effects of prostacyclin on the human brain following SAH. Methods: This trial is a single-centre, randomised, placebo-controlled, parallel group, blinded, clinical, pilot trial. A total of 90 patients with SAH will be randomised to one of three intervention arms: epoprostenol 1 ng/kg/min, epoprostenol 2 ng/kg/min or placebo in addition to standard treatment. Trial medication will start day 5 after SAH and continue to day 10. The primary outcome measure is changes in regional cerebral blood flow from baseline in the arterial territories of the anterior cerebral artery, medial cerebral artery and the posterior cerebral artery, measured by CT perfusion scan. The secondary outcomes will be vasospasm measured by CT angiography, ischaemic parameters measured by brain microdialysis, flow velocities in the medial cerebral artery, clinical parameters and outcome (Glasgow Outcome Scale) at 3 months.
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| 19. |
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| 20. |
- Sandestig, Anna, et al.
(författare)
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Therapeutic Hypothermia in Children and Adults with Severe Traumatic Brain Injury.
- 2014
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Ingår i: Therapeutic hypothermia and temperature management. - : Mary Ann Liebert Inc. - 2153-7933 .- 2153-7658. ; 4:1, s. 10-20
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Forskningsöversikt (refereegranskat)abstract
- Great expectations have been raised about neuroprotection of therapeutic hypothermia in patients with traumatic brain injury (TBI) by analogy with its effects after heart arrest, neonatal asphyxia, and drowning in cold water. The aim of this study is to review our present knowledge of the effect of therapeutic hypothermia on outcome in children and adults with severe TBI. A literature search for relevant articles in English published from year 2000 up to December 2013 found 19 studies. No signs of improvement in outcome from hypothermia were seen in the five pediatric studies. Varied results were reported in 14 studies on adult patients, 2 of which reported a tendency of higher mortality and worse neurological outcome, 4 reported lower mortality, and 9 reported favorable neurological outcome with hypothermia. The quality of several trials was low. The best-performed randomized studies showed no improvement in outcome by hypothermia-some even indicated worse outcome. TBI patients may suffer from hypothermia-induced pulmonary and coagulation side effects, from side effects of vasopressors when re-establishing the hypothermia-induced lowered blood pressure, and from a rebound increase in intracranial pressure (ICP) during and after rewarming. The difference between body temperature and temperature set by the biological thermostat may cause stress-induced worsening of the circulation and oxygenation in injured areas of the brain. These mechanisms may counteract neuroprotective effects of therapeutic hypothermia. We conclude that we still lack scientific support as a first-tier therapy for the use of therapeutic hypothermia in TBI patients for both adults and children, but it may still be an option as a second-tier therapy for refractory intracranial hypertension.
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