| 1. |
- 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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| 2. |
- 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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| 3. |
- 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
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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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| 4. |
- 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
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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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| 5. |
- 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
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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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| 6. |
- 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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| 7. |
- Holbeck, Staffan
(författare)
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Transvascular exchange and organ perfusion with reference to colloid and hypertonic solutions, and to endotoxaemia
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Changes in vascular permeability can immensely change plasma volume and affect the degree of oedema in the body. In diseases with an increased vascular permeability, adequate fluid therapy is of considerable importance to prevent hypovolaemia. Mechanisms behind differences in effectiveness of various plasma volume expanders to restore a low plasma volume and a compromised microcirculation are still not fully understood. This thesis based on experimental studies on cat, analysis colloid and hypertonic plasma volume expanders regarding their effects on transvascular fluid exchange and vascular permeability in skeletal muscle during and after discontinuation of the infusions. In addition, permeability effects are analysed in skeletal muscle following endotoxin infusion, as well as effects of plasma volume substitution on intestinal perfusion and metabolism in endotoxaemia. The autoperfused right hind limb skeletal muscle was enclosed in a plethysmograph allowing continuous measurements of tissue volume variations. Capillary filtration coefficient measurements showed that fluid permeability is decreased by albumin and dextran, unchanged by hydroxyethyl starch (HES), and increased by gelatin. Measurements of change in the reflection coefficient for albumin showed no direct effect on albumin permeability of dextran, gelatin, or hydroxyethyl starch. Hypertonic saline increased fluid permeability an effect not seen with mannitol and urea. Muscle volume was decreased by 20% albumin, unchanged by 6% dextran 70 and 6% HES 200/0.5, and increased by 3.5% gelatin. Gelatin and HES, but not dextran and albumin induced rebound filtration, indicating interstitial accumulation of the colloid molecules. Hypertonic saline, mannitol and urea induced absorption of which hypertonic saline was most effective and mannitol less effective over time in relation to osmotic capacity. Mannitol and urea but not hypertonic saline showed rebound filtration indicating intracellular accumulation of mannitol and urea. During endotoxaemia, both fluid and albumin permeability increased in skeletal muscle and hypovolaemia was shown to be the major, but probably not the only cause of disturbed intestinal perfusion. No difference could be seen between albumin, dextran, and hydroxyethyl starch in effectiveness to restore intestinal perfusion during endotoxaemia.
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