| 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. |
- 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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| 3. |
- 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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| 4. |
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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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| 11. |
- 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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| 12. |
- 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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| 13. |
- 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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| 14. |
- 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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| 15. |
- 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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| 16. |
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| 17. |
- 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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| 18. |
- 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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| 19. |
- Chesnut, Randall, et al.
(författare)
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A Consensus-based Interpretation of the BEST TRIP ICP Trial.
- 2015
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 32:22, s. 1722-1724
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Tidskriftsartikel (refereegranskat)abstract
- Widely varying published and presented analyses of the BEST TRIP randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi-method-based approach employed iterative pre-meeting polling to codify the groups general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of > 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83-100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that this study: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation and avoid "collateral damage".
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| 20. |
- 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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| 21. |
- 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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| 22. |
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| 23. |
- 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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| 24. |
- 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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| 25. |
- 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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| 26. |
- 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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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Grände, Per-Olof, et al.
(författare)
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Lund strikes again - Reply
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:10, s. 1281-1283
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 33. |
- 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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| 34. |
- 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
-
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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| 35. |
- 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
-
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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| 36. |
- 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
-
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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| 37. |
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| 38. |
- Grände, Per-Olof
(författare)
-
The lund concept for the treatment of patients with severe traumatic brain injury.
- 2011
-
Ingår i: Journal of Neurosurgical Anesthesiology. - : Ovid Technologies (Wolters Kluwer Health). - 1537-1921 .- 0898-4921. ; 23:4, s. 358-362
-
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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| 39. |
- Grände, Per-Olof
(författare)
-
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
-
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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| 40. |
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| 41. |
- Grände, Per-Olof, et al.
(författare)
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Treatment of intracranial hypertension and aspects on lumbar dural puncture in severe bacterial meningitis.
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:3, s. 264-270
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Brain stem herniation due to raised intracranial pressure (ICP) is a common cause of mortality in severe bacterial meningitis, but continuous measurements of ICP and the effects of ICP-reducing therapy in these patients have, to our knowledge, not been described. METHODS: During a four-year period, an ICP-monitoring device was implanted in patients admitted to our hospital with severe bacterial meningitis and suspected intracranial hypertension. ICP above 20 mmHg was treated using the Lund Concept, which includes antihypertensive therapy (beta1-antagonist,alpha2-agonist), normalization of the plasma colloid osmotic pressure and the blood volume, and antistress therapy. RESULTS: ICP above 20 mmHg was found in all 12 patients studied. It was effectively reduced in all but two patients, who died. Both patients had a low cerebral perfusion pressure (<10 mmHg), dilated pupils at start of therapy and were beyond recovery. Radiological signs of brain swelling were present in only five patients. Seven patients recovered fully, while mild audiological impairment was observed in two and minor neurological sequelae in one patient. Eight patients showed signs suggesting imminent brain stem herniation before start of ICP-reducing treatment, seven of whom had been subjected to diagnostic lumbar dural puncture shortly before development of the brain stem symptoms. These symptoms gradually regressed after initiation of therapy, and in one patient reversal of brain stem herniation was documented by MRI. CONCLUSIONS: Severe bacterial meningitis can be associated with increased ICP, which can be reduced using the Lund Concept. The high survival rate, the low frequency of sequelae and the reversal of signs of imminent brain stem herniation in these high-risk patients indicated beneficial effects of the intervention. The study confirms earlier observations that lumbar dural puncture is potentially hazardous in patients with intracranial hypertension, because it may trigger brain stem herniation. A normal CT brain scan does not rule out intracranial hypertension.
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| 42. |
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| 43. |
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| 44. |
- Grände, Per-Olof, et al.
(författare)
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Volume-targeted therapy of increased intracranial pressure: the Lund concept unifies surgical and non-surgical treatments
- 2002
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:8, s. 929-941
-
Forskningsöversikt (refereegranskat)abstract
- Opinions differ widely on the various treatment protocols for sustained increase in intracranial pressure (ICP). This review focuses on the physiological volume regulation of the intracranial compartments. Based on these mechanisms we describe a protocol called 'volume-targeted' ('Lund concept') for treatment of increased ICP. The driving force for transcapillary fluid exchange is determined by the balance between effective transcapillary hydrostatic and osmotic pressures. Fluid exchange across the intact blood-brain barrier (BBB) is counteracted by the low permeability to crystalloids (mainly Na+ and Cl-) combined with the high osmotic pressure (5500 mmHg) on both sides of the BBB. This contrasts to most other capillary regions where the osmotic pressure is mainly derived from the plasma proteins (approximately 25 mmHg). Accordingly, the level of the cerebral perfusion pressure (CPP) is of less importance under physiological conditions. In addition cerebral intracapillary hydrostatic pressure (and cerebral blood flow) is physiologically tightly autoregulated, and variations in systemic blood pressure are generally not transmitted to these capillaries. If the BBB is disrupted, transcapillary water transport will be determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Under these pathological conditions, pressure autoregulation of cerebral blood flow is likely to be impaired and intracapillary hydrostatic pressure will depend on variations in systemic blood pressure. The volume-targeted 'Lund concept' can be summarized under four headings: (1) Reduction of stress response and cerebral energy metabolism; (2) reduction of capillary hydrostatic pressure; (3) maintenance of colloid osmotic pressure and control of fluid balance; and (4) reduction of cerebral blood volume. The efficacy of the protocol has been evaluated in experimental and clinical studies regarding the physiological and biochemical (utilizing intracerebral microdialysis) effects, and the clinical experiences have been favorable.
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| 45. |
- Holbeck, Staffan, et al.
(författare)
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Dextran, gelatin, and hydroxyethyl starch do not affect permeability for albumin in cat skeletal muscle
- 2001
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Ingår i: Critical Care Medicine. - 1530-0293. ; 29:1, s. 123-128
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the effects of the three commercially available colloid solutions, 6% dextran 70, 6% hydroxyethyl starch (HES) 200/0.5, and 3.5% urea-linked gelatin on permeability for human albumin in a skeletal muscle in vivo model by evaluating their effects on the reflection coefficient for albumin. DESIGN: Controlled laboratory study. SETTING: University research laboratory. SUBJECTS: Eighteen adult cats. INTERVENTIONS: The autoperfused and denervated calf muscles of the cat hindlimb were placed in a plethysmograph. The transvascular fluid absorption induced by an increase in the colloid osmotic pressure following a fixed intravenous bolus of human albumin was analyzed, first before start of, and then during an intra-arterial infusion to, the muscle preparation of the synthetic colloid to be analyzed. Capillary filtration coefficient as a measure of microvascular fluid permeability (conductance) was analyzed before and after start of the synthetic colloid. MEASUREMENTS AND MAIN RESULTS: Arterial blood flow, arterial and venous blood pressures, total vascular resistance, tissue volume changes, capillary filtration coefficient, and plasma volume were measured before and during the colloid infusion. According to the Starling fluid equilibrium, the ratio between the reflection coefficients for albumin on two occasions (before and after infusion of the synthetic colloid) can be calculated from the maximum osmotic absorption rates induced by a fixed intravenous bolus infusion of albumin and from the capillary filtration coefficients. Obtained data were adjusted for different plasma volume at the two occasions. We found that none of the three synthetic colloids analyzed had any significant effect on the reflection coefficient for albumin. CONCLUSION: An effect on albumin microvascular permeability of the synthetic colloids dextran 70, HES 200/0.5, and urea-linked gelatin could not be shown by a method analyzing their effect on the reflection coefficient for albumin.
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| 46. |
- Holbeck, Staffan, et al.
(författare)
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Effects of hypertonic saline, mannitol, and urea with regard to absorption and rebound filtration in cat skeletal muscle.
- 2002
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Ingår i: Critical Care Medicine. - 1530-0293. ; 30:1, s. 212-217
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the effects of the hypertonic solutions 15% mannitol, 3% and 7.5% saline, and 30% urea at clinically relevant plasma concentrations with regard to absorption and rebound effects on tissue volume in skeletal muscle. DESIGN: A prospective, experimental study. SETTING: University laboratory. SUBJECTS: Twenty-eight anesthetized cats. INTERVENTIONS: The study was performed on an autoperfused and denervated cat calf muscle placed in a fluid-filled plethysmograph. Muscle volume changes and capillary filtration coefficient (reflecting capillary fluid conductivity) were measured before, during, and after intra-arterial infusion (4 mL/hr) of the hypertonic solutions. Mannitol and 3% saline have the same osmolality and were compared specifically in an attempt to distinguish osmotic effects from those specific to the compound. MEASUREMENTS AND MAIN RESULTS: All solutions reduced muscle volume during the infusion (p < .05). The maximum volume reduction persisted after 2 hrs of infusion for 3% and 7.5% saline, whereas there was a tendency for volume recovery during the urea infusion and a complete recovery back to control for mannitol. After discontinuation of the infusions, the muscle volume increased for all four solutions, stabilizing at the initial control for 3% and 7.5% saline, whereas it increased to levels above control for mannitol and urea (p < .05). Capillary filtration coefficient was increased by hypertonic saline (p < .05) but was unaffected by mannitol and urea. CONCLUSIONS: The effectiveness of a hypertonic solution in reducing tissue volume and its tendency to cause a rebound volume increase depends not only on the osmolality of the solution. Hypertonic saline may in the long run be superior to mannitol and urea to increase plasma volume or decrease tissue volume of an organ, because it lacks rebound effects. Alterations in capillary filtration coefficient (fluid conductivity) may reflect volume changes of the capillary endothelial cell and thereby differences in cell membrane permeability for the hypertonic solutions, also consistent with the obtained differences in tissue volume effects.
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| 47. |
- Holbeck, Staffan, et al.
(författare)
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Endotoxin increases both protein and fluid microvascular permeability in cat skeletal muscle
- 2003
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Ingår i: Critical Care Medicine. - 1530-0293. ; 31:2, s. 560-565
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate effects of lipopolysaccharide (endotoxin) on protein and fluid permeability in a whole organ skeletal muscle preparation. Design: Controlled, prospective laboratory study. Setting: University research laboratory. Subjects: Eleven adult male cats. Interventions: The study was performed on the autoperfused and denervated calf muscles of the cat hindlimb placed in a fluid-filled plethysmograph. The endotoxin-induced change in the osmotic reflection coefficient for albumin was used as a measure of alteration in protein permeability of the microvascular wall, and the simultaneous change in capillary filtration coefficient was used as a measure of alteration in fluid permeability. Endotoxin as a bolus infusion (1 mg/kg iv) was given to six cats, and another five cats given only the vehicle (NaCl) were used as control. Measurements and Main Results: Arterial blood flow, arterial and venous blood pressures, total vascular resistance, and tissue volume changes were measured continuously. The ratio between the osmotic reflection coefficients for albumin on two occasions (before and about 1.5 hr after endotoxin infusion) was calculated from the Starling fluid equilibrium equation. This was performed by measurement of the maximum absorption rate from an iso-volumetric state by an intravenous bolus infusion of 20% human albumin (0.6 g/kg) and the capillary filtration coefficient. Albumin concentrations were measured before and after the albumin infusion to correct for effects of difference in plasma volume on the induced increase in colloid osmotic pressure. We found that the osmotic reflection coefficient for albumin was reduced by 30% (p < .05), and the capillary filtration coefficient was increased by 31% (p < .05) by endotoxin. No changes were seen in the vehicle experiments. Conclusion: Endotoxin causes a significant increase in both protein and fluid microvascular wall permeability. These effects may explain the marked leakage of plasma to the interstitium that is often seen in critically ill patients with sepsis and systemic inflammatory response syndrome.
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| 48. |
- Holbeck, Staffan, et al.
(författare)
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Hypovolemia is a main factor behind disturbed perfusion and metabolism in the intestine during endotoxemia in cat.
- 2002
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Ingår i: Shock. - 1540-0514. ; 18:4, s. 367-373
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Tidskriftsartikel (refereegranskat)abstract
- Disturbances in intestinal metabolism and perfusion during SIRS can be direct effects of toxic substances, and/or effects secondary to hypovolemia. An attempt to evaluate the significance of hypovolemia for intestinal disturbances during SIRS was made in the present study on feline by evaluating the degree to which the intestinal alterations following endotoxin infusion were restored by a clinically relevant volume infusion. The results were compared with control animals treated identically except that they were not given a volume infusion. We analyzed effects of a colloid infusion during endotoxemia on intestinal perfusion, and on the metabolites lactate, pyruvate, glucose, and glycerol in the intestinal wall, the latter by a microdialysis technique. Arterial and central venous blood pressures, and superior mesenteric artery blood flow were measured, and intestinal oxygen delivery and uptake were calculated. To evaluate to what extent a restoring effect of a colloid infusion was dependent on the type of colloid solution used, three different colloids with about the same volume expanding effects (6% albumin, 6% dextran 70 and 6% hydroxyethyl starch, n = 3 x 6) were tested randomly and blinded. Four hrs after start of endotoxin (1 mg/kg + 1 mg/kg/h), the colloid was infused at a rate of 5 mL/kg for 30 min followed by 2.5 mL/kg/h. Endotoxin caused a marked deterioration of perfusion and metabolic parameters. Most of these parameters turned towards normalization, though not fully reaching baseline values within 4 hrs after start of the colloid infusion. In the control experiments (n = 4), the endotoxin-induced deteriorations persisted or were aggravated during the corresponding time period. The results indicated that hypovolemia is an essential factor but not the only one behind alterations in metabolism and perfusion in the intestine during SIRS, and the alterations can be significantly reduced by adequate volume substitution. In this respect no differences could be seen between the three colloids tested.
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| 49. |
- Jahr, John, et al.
(författare)
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In vivo effects of prostacyclin on segmental vascular resistances, on myogenic reactivity, and on capillary fluid exchange in cat skeletal muscle
- 1995
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Ingår i: Critical Care Medicine. - 1530-0293. ; 23:3, s. 523-531
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the local circulatory effects of prostacyclin in skeletal muscle. DESIGN: A prospective experimental study. SETTING: A university laboratory. SUBJECTS: Twelve adult cats. INTERVENTIONS: The study was performed on autoperfused, sympathectomized gastrocnemius muscle. MEASUREMENTS AND MAIN RESULTS: Arterial blood flow, total and segmental vascular resistances (arterial vessels of > 25 microns, arterioles of < 25 microns, and veins), hydrostatic capillary pressure, tissue volume, myogenic reactivity, and the capillary filtration coefficient were followed. The capillary filtration coefficient reflects the functional capillary fluid exchange area. Myogenic reactivity was evaluated as the arteriolar resistance increase after a standardized decrease in extravascular pressure. Arterial infusion of prostacyclin decreased vascular resistance by approximately 50% at the highest dose given (500 ng/kg/min). This effect was more pronounced on the arterial side, especially in arterial vessels of > 25 microns. Hydrostatic capillary pressure increased by 1.9 +/- 0.3 mm Hg, causing fluid filtration. The relative fluid filtration was less than that value shown for some other vasodilator drugs (isoprenaline, calcium-channel blockers, thiopental) in this muscle preparation. Capillary filtration coefficient decreased by 25%. Myogenic reactivity was depressed but to a lesser extent than previously observed for other vasodilator mechanisms (muscle exercise, beta-adrenergic receptor stimulation, thiopental infusion, nifedipine infusion). CONCLUSIONS: Prostacyclin is a vasodilator, both on the arterial and venous side, that restricts the increase in hydrostatic capillary pressure. The decrease in capillary filtration coefficient most likely reflects a decrease in capillary permeability, explaining the smaller relative filtration rate. The relatively well-preserved myogenic reactivity may imply a better preserved microvascular flow distribution and peripheral oxygen uptake.
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| 50. |
- 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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