| 1. |
- Overgaard-Steensen, Christian, et al.
(författare)
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Edelman's equation is valid in acute hyponatremia in a porcine model : plasma sodium concentration is determined by external balances of water and cations
- 2010
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 298:1, s. R120-R129
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Tidskriftsartikel (refereegranskat)abstract
- Acute hyponatremia is a serious condition, which poses major challenges. Of particular importance is what determines plasma sodium concentration ([Na(+)]). Edelman introduced an explicit model to describe plasma [Na(+)] in a population as [Na(+)] = alpha.(exchangeable Na(+) + exchangeable K(+))/(total body water) - beta. Evidence for the clinical utility of the model in the individual and in acute hyponatremia is sparse. We, therefore, investigated how the measured plasma [Na(+)] could be predicted in a porcine model of hyponatremia. Plasma [Na(+)] was estimated from in vivo-determined balances of water, Na(+), and K(+), according to Edelman's equation. Acute hyponatremia was induced with desmopressin acetate and infusion of a 2.5% glucose solution in anesthetized pigs. During 480 min, plasma [Na(+)] and osmolality were reduced from 136 (SD 2) to 120 mmol/l (SD 3) and from 284 (SD 4) to 252 mosmol/kgH(2)O (SD 5), respectively. The following interpretations were made. First, Edelman's model, which, besides dilution, takes into account Na(+) and K(+), fits plasma [Na(+)] significantly better than dilution alone. Second, a common value of alpha = 1.33 (SD 0.08) and beta = -13.04 mmol/l (SD 7.68) for all pigs explains well the plasma [Na(+)] in the individual animal. Third, measured exchangeable Na(+) and calculated exchangeable Na(+) + K(+) per weight in the pigs are close to Edelman's findings in humans, whereby the methods are cross-validated. In conclusion, plasma [Na(+)] can be explained in the individual animal by external balances, according to Edelman's construct in acute hyponatremia.
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| 2. |
- Overgaard-Steensen, Christian, et al.
(författare)
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Regional differences in osmotic behavior in brain during acute hyponatremia : an in vivo MRI-study of brain and skeletal muscle in pigs
- 2010
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 299:2, s. R521-R532
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Tidskriftsartikel (refereegranskat)abstract
- Brain edema is suggested to be the principal mechanism underlying the symptoms in acute hyponatremia. Identification of the mechanisms responsible for global and regional cerebral water homeostasis during hyponatremia is, therefore, of utmost importance. To examine the osmotic behavior of different brain regions and muscles, in vivo-determined water content (WC) was related to plasma sodium concentration ([Na(+)]) and brain/muscle electrolyte content. Acute hyponatremia was induced with desmopressin acetate and infusion of a 2.5% glucose solution in anesthetized pigs. WC in different brain regions and skeletal muscle was estimated in vivo from T(1) maps determined by magnetic resonance imaging (MRI). WC, expressed in gram water per 100 g dry weight, increased significantly in slices of the whole brain [342(SD = 14) to 363(SD = 21)] (6%), thalamus [277(SD = 13) to 311(SD = 24)] (12%) and white matter [219(SD = 7) to 225(SD = 5)] (3%). However, the WC increase in the whole brain and white mater WC was less than expected from perfect osmotic behavior, whereas in the thalamus, the water increase was as expected. Brain sodium content was significantly reduced. Muscle WC changed passively with plasma [Na(+)]. WC determined with deuterium dilution and tissue lyophilzation correlated well with MRI-determined WC. In conclusion, acute hyponatremia induces brain and muscle edema. In the brain as a whole and in the thalamus, regulatory volume decrease (RVD) is unlikely to occur. However, RVD may, in part, explain the observed lower WC in white matter. This may play a potential role in osmotic demyelination.
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| 3. |
- Overgaard-Steensen, Christian, et al.
(författare)
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The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss
- 2016
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Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 101:7, s. 932-945
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Tidskriftsartikel (refereegranskat)abstract
- Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (I.P. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an I.P. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single I.V. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28%). Sodium was redistributed to the peritoneal fluid, resulting in a significantly reduced plasma volume. This shows that the I.P. model induces hypovolaemic hyponatraemia and not dilutional/SIADH hyponatraemia. Brain oedema evolved, but brain sodium content decreased significantly (by 21%). To conclude, the I.P. model induces hypovolaemic hyponatraemia attributable to sodium redistribution and not water dilution. The large reduction in brain sodium is probably attributable to the specific mechanism that causes the hyponatraemia. This is not accounted for in the current understanding of the brain response to acute hyponatraemia.
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