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- Drobin, D, et al.
(författare)
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Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4)
- 2004
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 96:5, s. 1843-1853
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free Hb increases systemic and pulmonary pressure and resistance and reduces cardiac output and heart rate in animals and humans, effects that have limited their clinical development as “blood substitutes.” The primary aim of this study was to evaluate the hemodynamic response to infusion of several formulations of a new polyethylene glycol (PEG)-modified human Hb [maleimide PEG Hb (MalPEGHb)] in swine, an animal known to be sensitive to Hb-induced vasoconstriction. Anesthetized animals underwent controlled hemorrhage (50% of blood volume), followed by resuscitation (70% of shed volume) with 10% pentastarch (PS), 4% MalPEG-Hb in lactated Ringer (MP4), 4% MalPEG-Hb in pentastarch (HS4), 2% MalPEG-Hb in pentastarch (HS2), or 4% stroma-free Hb in lactated Ringer solution (SFH). Compared with baseline, restoration of blood volume after resuscitation was similar and not significantly different for the PS (103%), HS2 (99%), HS4 (106%), and MP4 (87%) animals but significantly less for the SFH animals (66%) ( P < 0.05). All solutions that contained MalPEG-Hb restored mean arterial and pulmonary pressure and cardiac output. Systemic vascular resistance was unchanged, and pulmonary arterial pressure and resistance were increased slightly. Both systemic and pulmonary vascular resistance increased significantly in animals that received SFH, despite less adequate blood volume restoration. Oxygen consumption was maintained in all animals that received MalPEG-Hb, but not PS. Base excess improved only with MalPEG-Hb and PS, but not SFH. Red blood cell O2extraction was significantly increased in animals that received Hb, regardless of formulation. These data demonstrate resuscitation with MalPEG-human Hb without increasing systemic vascular resistance and support our previous observations in animals suggesting that the efficacy of low concentrations of PEG-Hb in the plasma results from reduced vasoconstriction.
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- Sonden, A, et al.
(författare)
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Proinflammatory reaction and cytoskeletal alterations in endothelial cells after shock wave exposure
- 2006
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Ingår i: Journal of investigative medicine : the official publication of the American Federation for Clinical Research. - : SAGE Publications. - 1081-5589. ; 54:5, s. 262-271
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Tidskriftsartikel (refereegranskat)abstract
- Although the effects on human organs by shock waves (SWs) induced by medical treatments or high-energy trauma are well recognized, little is known about the effects on the cellular level. Since blood vessel injury is a common finding after SW exposure, we assessed the in vitro effects of SWs on human umbilical vein endothelial cells (HUVECs). Methods An in vitro trauma model was used to expose HUVEC monolayers to focused SWs or to shock waves plus cavitation (SWC), a subsequent phenomenon that is often considered the main cause of SW vascular injury. Results SWs alone did not cause any changes in the studied variables. In contrast, HUVEC monolayers exposed to SWC exhibited discrete central lesions with extensive cell death. Cells peripheral to the main lesion area displayed disassembly of dense peripheral bands and formation of actin stress fibers, indicating increased intercellular gaps. Expression of P-selectin was enhanced 11-fold compared with controls, whereas expression of E-selectin and intercellular adhesion molecule 1 was enhanced 8-fold ( p < .05) and 1.5-fold ( p < .01), respectively. The latter responses were preceded by nuclear translocation of nuclear factor κB subunit p65 by 16% ( p < .01). When compared with mechanically produced lesions used as controls, SWC lesions exhibited an impaired regeneration rate of the endothelial cell layer ( p < .001). Redistribution of centrosomes toward the lesion borders was less effective in the SWC samples compared with the mechanically produced lesions ( p < .01). Conclusions SWC lesions were associated with a switch to an endothelial proinflammatory phenotype, with an impaired regeneration rate and changes in cytoskeletal functions.
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