| 1. |
- Mårtensson, Ulrika, et al.
(författare)
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Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
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Tidskriftsartikel (refereegranskat)abstract
- In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
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| 2. |
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| 3. |
- Dubniks, Maris, et al.
(författare)
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Change in plasma volume from a state of hyper-, normo- or hypovolemia with or without noradrenalin infusion in the rat.
- 2008
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 76, s. 75-79
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Tidskriftsartikel (refereegranskat)abstract
- Fluid substitution is important in critically ill patients to maintain normovolemia, but there is always a risk that the treatment is too aggressive resulting in fluid overload, or is insufficient with maintenance of hypovolemia. The present study on the rat aims at evaluating the change in plasma volume after 2.5 h from a state of hyper- and hypovolemia. The analysis was made without and with noradrenalin infusion, based on the fact that noradrenalin infusion is a common drug to maintain an adequate arterial pressure, and noradrenalin may induce transcapillary filtration. Plasma volume was determined at baseline and at the end of the experiments with a (125)I-albumin tracer technique. Arterial and central venous pressure, and urine output were recorded. We showed that induction of hypervolemia with a 5% albumin solution (15 ml/kg) resulted in successive loss of plasma volume, which was aggravated with noradrenalin infusion. Hypovolemia induced by hemorrhage (15 ml/kg) resulted in transcapillary absorption, an absorption almost abolished during noradrenalin infusion. There was no plasma volume loss in the sham group. Urine output was higher under hypervolemia than under normovolemia, which in turn was higher than under hypovolemia. We conclude that hypervolemia induces plasma volume loss, which is aggravated by noradrenalin infusion. The compensatory absorption effect after hemorrhage is counteracted by noradrenalin. The results can be explained by differences in hydrostatic capillary pressure via alterations in arterial and venous pressure, according to the 2-pore theory of transcapillary fluid exchange.
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| 4. |
- Dubniks, Maris, et al.
(författare)
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Comparison of the plasma volume-expanding effects of 6% dextran 70, 5% albumin, and 6% HES 130/0.4 after hemorrhage in the guinea pig.
- 2009
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Ingår i: The Journal of trauma. - 1529-8809. ; 67:6, s. 1200-1204
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We still lack comparing data of the plasma volume (PV)-expanding effect of the most commonly used colloids including dextran 70. This study compares the PV-expanding effects of 6% dextran 70, 5% albumin, and 6% hydroxyethylstarch (HES) 130/0.4 after a standardized hemorrhage. METHODS: The prospective and randomized study on 33 anesthetized adult male guinea pigs involved three groups (n = 11 each); the dextran group, the albumin group, and the HES group. The left carotis artery was cannulated for blood pressure measurements and blood samples, and the right jugular vein was cannulated for infusions. After hemorrhage of 20 mL/kg for 8 minutes, the animals were transfused with 20 mL/kg of the colloid for 10 minutes. PV was determined with a I-albumin tracer dilution technique at baseline and 3 hours after the colloid infusion. The PV just after hemorrhage was calculated as the baseline value minus bled PV. Blood gases were measured at baseline, after hemorrhage, just after the colloid infusion and at the end of the experiment. RESULTS: The increase in PV 3 hours after the colloid infusion, including the 20 mL infused, was 36.3 mL/kg +/- 2.3 mL/kg in the dextran group, 26.4 mL/kg +/- 4.7 mL/kg in the albumin group, and 17.6 mL/kg +/- 3.5 mL/kg in the HES group. At the end of the experiment, hematocrit was lower in the dextran group than in the albumin and the HES groups. Urine production was higher in the HES group than in the dextran and the albumin groups. CONCLUSION: After hemorrhage, the PV-expanding capacity of 6% dextran 70 was better than that of 5% albumin, which was in turn better than that of HES 130/0.4 given in equal volumes.
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| 5. |
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| 6. |
- Dubniks, Maris, et al.
(författare)
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Plasma volume expansion of 5% albumin, 4% gelatin, 6% HES 130/0.4, and normal saline under increased microvascular permeability in the rat.
- 2007
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 33:2, s. 293-299
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the colloids 5% albumin, 4% gelatin, and 6% HES 130/0.4 with one another and with normal saline regarding their plasma expanding effects at increased permeability and to compare the results with those from a previous study at normal permeability. Design and setting: Prospective controlled randomized laboratory study in a university research laboratory. Subjects: 48 adult male Sprague-Dawley rats. Interventions: Permeability was increased by an injection of 0.5 ml dextran 70 using the fact that dextran causes anaphylactic reaction in the rat. Plasma volume was determined (I-125 albumin tracer technique) after anesthesia, 1 h after dextran injection (before infusion for 10-15 min of 20 ml/kg bw of each of the colloids or 80 ml/kg saline), and 3 h later. Blood pressure, hematocrit, blood gases, and electrolytes were measured. CVP was measured in four rats. Measurements and results: Plasma volume was 41.1 +/- 1.9 ml/kg at baseline (n = 9), and 29.1 +/- 4.1 ml/kg (n = 35) 1 h after the dextran injection. Three hours after infusion of the plasma expander plasma volume had increased by 17.1 +/- 3.4 ml/kg in the albumin group, 7.9 +/- 3.6 ml/kg in the gelatin group, 7.4 +/- 4.4 ml/kg in the HES group, and 12.2 +/- 3.1 ml/kg in the saline group. It was unchanged in a control group given no solution (n = 7 for all groups). Conclusion: Albumin was a more effective plasma volume expander than gelatin or HES or saline (saline in 4 times larger volume). Gelatin and HES were equally effective. All solutions showed a smaller plasma expanding effect than observed in a previous study with normal permeability.
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| 7. |
- Dubniks, Maris, et al.
(författare)
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The effects of activated protein C and prostacyclin on arterial oxygenation and protein leakage in the lung and the gut under endotoxaemia in the rat.
- 2008
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 52, s. 381-387
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Tidskriftsartikel (refereegranskat)abstract
- Background: Based on the anti-adhesive/anti-aggregatory and permeability-reducing properties of activated protein C (APC) and prostacyclin (PGI(2)), we analysed and compared these substances regarding their efficacy in counteracting transcapillary leakage of albumin in the lung and the gut, and in improving arterial oxygenation under a condition of inflammation. Methods: The randomized and blinded study was performed on 31 adult male Sprague-Dawley rats. Inflammation was induced by continuous infusion of Escherichia coli endotoxin (lipopolysaccharide, LPS). Six hours after the start of the LPS infusion (240,000 U/kg/h), a simultaneous infusion of saline (control group) or 8 mug/kg/min of human recombinant APC or 2 ng/kg/min of PGI(2) was started and continued for 24 h (n=8 per group). The study also included a sham group. Transcapillary leakage of albumin was measured from the ratio between tissue radioactivity [counts per minute (cpm)/g tissue] and actual amount of radioactivity given (cpm/g body weight of (125)I-albumin). Oxygenation was assessed from arterial and central venous blood samples. Results: LPS induced albumin leakage in the gut and the lung, and impaired blood oxygenation. In the lung, the leakage was lower in the PGI(2) group than in the APC and the control groups (P<0.05). In the gut, it was lower in the APC and the PGI(2) groups than in the control group (P<0.05). Oxygenation was better in the APC and PGI(2) groups than in the control group. Conclusion: Our data suggest that both APC and low-dose PGI(2) are beneficial in LPS-induced inflammation in the rat, by reducing albumin leakage and improving blood oxygenation.
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| 8. |
- Grände, Per-Olof, et al.
(författare)
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Active cooling in traumatic brain-injured patients: a questionable therapy?
- 2009
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 53, s. 1233-1238
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia is shown to be beneficial for the outcome after a transient global brain ischaemia through its neuroprotective effect. Whether this is also the case after focal ischaemia, such as following a severe traumatic brain injury (TBI), has been investigated in numerous studies, some of which have shown a tendency towards an improved outcome, whereas others have not been able to demonstrate any beneficial effect. A Cochrane report concluded that the majority of the trials that have already been published have been of low quality, with unclear allocation concealment. If only high-quality trials are considered, TBI patients treated with active cooling were more likely to die, a conclusion supported by a recent high-quality Canadian trial on children. Still, there is a belief that a modified protocol with a shorter time from the accident to the start of active cooling, longer cooling and rewarming time and better control of blood pressure and intracranial pressure would be beneficial for TBI patients. This belief has led to the instigation of new trials in adults and in children, including these types of protocol adjustments. The present review provides a short summary of our present knowledge of the use of active cooling in TBI patients, and presents some tentative explanations as to why active cooling has not been shown to be effective for outcome after TBI. We focus particularly on the compromised circulation of the penumbra zone, which may be further reduced by the stress caused by the difference in thermostat and body temperature and by the hypothermia-induced more frequent use of vasoconstrictors, and by the increased risk of contusional bleedings under hypothermia. We suggest that high fever should be reduced pharmacologically.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Grände, Per-Olof
(författare)
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Mechanisms behind postspinal headache and brain stem compression following lumbar dural puncture - a physiological approach.
- 2005
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 49:5, s. 619-626
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Tidskriftsartikel (refereegranskat)abstract
- Background: The cause of postspinal headache and its specific characteristics are unknown, and whether lumbar dural puncture (LP) triggers brain-stem compression in patients with brain oedema is still controversial. Methods: Hydrostatic effects of distal opening of the dural sac towards the atmosphere are described and applied to the normal brain and the brain with disrupted BBB. Analogue analyses from previous results using an isolated skeletal muscle enclosed in a rigid shell were applied to the brain in an attempt to simulate and verify the haemodynamic effects of distal opening of the spinal canal. Results: The theoretical considerations and the experimental results are compatible with the hypothesis that hydrostatic effects of distal opening of the fluid-filled spinal canal may obliterate the normal subdural venous collapse after a change from the horizontal to vertical position, which may be compatible with postural postspinal headache as occurring close to pain-sensitive meningeal regions. The hydrostatic forces may also initiate transcapillary filtration and aggravate oedema when permeability is increased, which may cause a narrower situation in the brain stem region, perhaps aggravated by venous stasis and a Cushing reflex-induced increase in blood pressure. An magnetic resonance imaging (MRI) picture illustrates how this scenario may separate the subdural space into an upper high- and a lower low-pressure cavity, pressing the brain downwards with sagging of the brain. A life-threatening positive feedback situation for brain-stem compression may develop. Conclusion: The present study strongly suggests that postspinal headache and brain-stem compression and other LP-related effects are predictable following LP, without involving CSF leakage, and can be explained by hydrostatic effects triggered by distal opening of the normally closed dural space to the atmosphere.
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| 13. |
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| 14. |
- Grände, Per-Olof
(författare)
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The "Lund Concept" for the treatment of severe head trauma - physiological principles and clinical application.
- 2006
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 32:10, s. 1475-1484
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Forskningsöversikt (refereegranskat)abstract
- The Lund Concept is an approach to the treatment of severe brain trauma that is mainly based on hypotheses originating from basic physiological principles regarding brain volume and cerebral perfusion regulation. Its main attributes have found support in experimental and clinical studies. This review explains the principles of the Lund Concept and is intended to serve as the current guide for its clinical application. The therapy has two main goals: (1) to reduce or prevent an increase in ICP (ICP-targeted goal) and (2) to improve perfusion and oxygenation around contusions (perfusion-targeted goal). The Lund therapy considers the consequences of a disrupted blood-brain barrier for development of brain oedema and the specific consequences of a rigid dura/cranium for general cerebral haemodynamics. It calls attention to the importance of improving perfusion and oxygenation of the injured areas of the brain. This is achieved by normal blood oxygenation, by maintaining normovolaemia with normal haematocrit and plasma protein concentrations, and by antagonizing vasoconstriction through reduction of catecholamine concentration in plasma and sympathetic discharge (minimizing stress and by refraining from vasoconstrictors and active cooling). The therapeutic measures mean normalization of all essential haemodynamic parameters (blood pressure, plasma oncotic pressure, plasma and erythrocyte volumes, PaO2, PaCO2) the use of enteral nutrition, and avoidance of overnutrition. To date, clinical outcome studies using the Lund Concept have shown favourable results.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Jungner, Mårten, et al.
(författare)
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Prostacyclin reduces elevation of intracranial pressure and plasma volume loss in lipopolysaccharide-induced meningitis in the cat.
- 2009
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Ingår i: The Journal of trauma. - 1529-8809. ; 67:6, s. 1345-1351
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Severe meningitis may compromise cerebral perfusion through increases in intracranial pressure (ICP) and through hypovolemia caused by a general inflammation with systemic plasma leakage. From its antiaggregative/antiadhesive and permeability-reducing properties, prostacyclin (PGI2) is a potential adjuvant treatment in meningitis, but previously published data have been ambiguous. The objective of this study was to evaluate the effects of PGI2 on meningitis on ICP, plasma volume, blood pressure, and cerebral oxidative metabolism. METHODS: Meningitis was induced by intrathecal injection of lipopolysaccharide (LPS, 0.8 x 10 units/kg) in cats. Four hours after the injection, the animals were randomized to intravenous treatment with either low-dose PGI2 (1 ng/kg/min) or the vehicle for 6 hours (n = 7 in each group). No LPS and no PGI2 or vehicle was given to three cats (sham group). Effects of treatment on ICP, mean arterial pressure, plasma volume (I-albumin technique), and brain tissue lactate/pyruvate ratio (microdialysis technique) were evaluated. RESULTS: ICP increased from 10.0 mm Hg +/- 1.3 mm Hg and 10.8 mm Hg +/- 1.7 mm Hg to 19.9 mm Hg +/- 1.7 mm Hg and 19.6 mm Hg +/- 3.3 mm Hg in the PGI2 and the vehicle group, respectively, 4 hours after the LPS injection (not significant). ICP increased further to 21.8 mm Hg +/- 4.5 mm Hg and to 25.8 mm Hg +/- 6.0 mm Hg after treatment for 6 hours with PGI2 or vehicle, respectively (p < 0.05). There was no significant difference in arterial pressure between groups. Plasma volume loss was less in the PGI2 group than in the vehicle group at the end of the experiment and urine production and arterial oxygenation was higher in the PGI2 group. Lactate/pyruvate ratio was within the normal range in all groups. CONCLUSION: Low-dose PGI2 may be a beneficial adjuvant therapy for meningitis by reducing elevation of ICP and plasma volume loss.
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| 19. |
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| 20. |
- Lundblad, Cornelia, et al.
(författare)
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Hemodynamic and histological effects of traumatic brain injury in eNOS-deficient mice.
- 2009
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 26:11, s. 1953-1962
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Tidskriftsartikel (refereegranskat)abstract
- Microvascular dysfunction in the brain, characterized by vasoconstriction, vascular occlusion, and disruption of the blood brain barrier, may adversely affect outcome following traumatic brain injury (TBI). Because of its vasodilating and antiaggregative properties, nitric oxide (NO) produced by nitric oxide synthase in the endothelium (eNOS) is a key regulator of vascular homeostasis. The objective of the present study was to evaluate the role of eNOS in vascular disturbances and histological outcome in the brain following TBI. Cortical blood flow ([(14)C]-iodoantipyrine technique), number of perfused capillaries (FITC-dextran technique), brain water content (wet vs. dry weight), and the transfer constant (K(i)) for [(51)Cr]-EDTA, reflecting permeability, were analyzed 3 h and 24 h after a controlled cortical impact injury (CCI) in eNOS-deficient (eNOS-KO) and wild-type (WT) mice. Cortical contusion volume and cell count in the hippocampus were evaluated 3 weeks after injury. Blood flow in the injured cortex decreased in both groups following trauma. There were no significant differences between the groups at 3 h, but blood flow was lower in eNOS-KO mice than in WT mice 24 h after trauma. Brain water content was higher in the WT mice than in eNOS-KO mice at 24 h. Number of perfused capillaries, K(i), and histological outcome were similar in both groups. We conclude that eNOS is important for maintenance of cerebral blood flow after trauma and that eNOS promotes edema formation by mechanisms other than increased permeability. The vascular effects of eNOS do not, however, influence histological outcome.
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| 21. |
- Lundblad, Cornelia, et al.
(författare)
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Increased cortical cell loss and prolonged hemodynamic depression after traumatic brain injury in mice lacking the IP receptor for prostacyclin.
- 2008
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 28:2, s. 367-376
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Tidskriftsartikel (refereegranskat)abstract
- Prostacyclin is the major arachidonic acid metabolite of the vascular endothelium and is produced mainly via the cyclooxygenase-2 pathway. By acting on the prostacyclin (IP) receptor on platelets and vascular smooth muscle cells, prostacyclin exerts vasodilatory and antiaggregative/antiadhesive effects. Previous studies have shown that prostacyclin production increases after brain trauma, but the importance of prostacyclin for posttraumatic hemodynamic alterations and neuron survival has not been investigated. This study evaluated if endogenous prostacyclin plays a role in the pathophysiologic process in the brain after brain trauma. This was performed by comparing prostacyclin (IP) receptor-deficient (IP-/-) mice and mice with functional IP receptor (IP+/+) after a controlled cortical injury regarding contusion volume, cerebral blood flow ([14C]iodoantipyrine autoradiography), number of perfused capillaries (fluorescein isothiocyanate-dextran fluorescence technique), the transfer constant (Ki) for [51Cr]EDTA, and brain water content (wet vs dry weight) in the injured and contralateral cortex. Contusion volume was increased in IP-/- mice compared with IP+/+ mice. Three hours after trauma, cortical blood flow was decreased in the injured cortex of both groups and the reduction in blood flow in the cortex of the IP-/- mice persisted from 3 to 24 h, whereas blood flow approached normal values in the IP+/+ mice after 24 h. No differences could be detected between the two genotypes regarding other hemodynamic parameters. We conclude that the prostacyclin IP receptor is beneficial for neuron survival after brain trauma in mice, an effect that may be mediated by improved cortical perfusion.
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| 22. |
- Persson, Johan, et al.
(författare)
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Plasma volume expansion and transcapillary fluid exchange in skeletal muscle of albumin, dextran, gelatin, hydroxyethyl starch, and saline after trauma in the cat
- 2006
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Ingår i: Critical Care Medicine. - 1530-0293. ; 34:9, s. 2456-2462
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare 5% albumin, 6% dextran 70, 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline regarding their plasma volume expanding effect after a surgical skeletal muscle trauma and their simultaneous effects on transvascular fluid exchange in skeletal muscle. Design: Controlled, prospective, randomized laboratory study. Setting: University research laboratory. Subjects: Thirty-six adult cats. Interventions: Systemic arterial pressure and tissue volume variations of and blood flow to a surgically isolated and autoperfused calf muscle placed in a plethysmograph were recorded. Arterial and venous pressures to the muscle were kept constant. After preparation, plasma volumes were determined by a 125 1 albumin tracer technique just before and 3 hrs after a bolus infusion of the plasma expander (25 mL/kg). Measurements and Main Results: Plasma volume was 20.9 +/- 2.9 mL/kg (n = 36) just before infusion of the plasma expander (normal plasma volume for the cat is 34-37 mL/kg). The remaining volume expansion of the infusion after 3 hrs was 6.8 mL/kg for albumin, 11.2 mL/kg for dextran, 1.8 mL/kg for gelatin, 2.2 mL/kg for hydroxyethyl starch, and 0.9 mL/kg for saline. Plasma volume decreased by 1.1 mL/kg when no solution was given (n = 6 per group). Colloid osmotic pressure was better preserved with dextran and albumin than with the other solutions. Albumin and dextran reduced muscle volume by absorption after 3 hrs, whereas the initial absorption turned to net filtration in the gelatin and hydroxyethyl starch groups. Saline infusion increased muscle volume by filtration for about 20 mins, followed by an approximately constant volume. Conclusion: The relatively poor plasma expansion for all solutions analyzed can most likely be explained by increased transcapillary leakage due to increased microvascular permeability following trauma. Under such circumstances, for equal volumes, plasma expansion was better preserved with 6% dextran 70 than with 5% albumin, which was better than 3.5% gelatin, 6% hydroxyethyl starch 130/0.4, and saline.
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| 23. |
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