VASCULAR PERMEABILITY INCREASE AND PLASMA VOLUME LOSS INDUCED BY ENDOTOXIN WAS ATTENUATED BY HYPERTONIC SALINE WITH OR WITHOUT DEXTRAN

Shock ◽  
1999 ◽  
Vol 12 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Helena de Carvalho ◽  
Juliana A. Matos ◽  
Eliete Bouskela ◽  
Erik Svensjö
Author(s):  
J. Siggaard-Andersen ◽  
F. Bonde Petersen ◽  
Thorsten Hansen ◽  
K. Mellemgaard

2002 ◽  
Vol 96 (6) ◽  
pp. 1371-1380 ◽  
Author(s):  
Dan Drobin ◽  
Robert G. Hahn

Background Major differences in plasma volume expansion between infusion fluids are fairly well known, but there is a lack of methods that express their dynamic properties. Therefore, a closer description enabled by kinetic modeling is presented. Methods Ten healthy male volunteers received, on different occasions, a constant-rate intravenous infusion over 30 min consisting of 25 ml/kg of 0.9% saline, lactated Ringer's solution, acetated Ringer's solution, 5 ml/kg of 7.5% saline, or 3 ml/kg of 7.5% saline in 6% dextran. One-, two-, and three-volume kinetic models were fitted to the dilution of the total venous hemoglobin concentration over 240 min. Osmotic fluid shifts were considered when hypertonic fluid was infused. Results All fluids induced plasma dilution, which decreased exponentially after the infusions. The ratio of the area under the dilution-time curve and the infused fluid volume showed the following average plasma-dilution dose-effect (efficiency), using 0.9% saline as the reference (= 1): lactated Ringer's solution, 0.88; acetated Ringer's solution, 0.91; hypertonic saline, 3.97; and hypertonic saline in dextran, 7.22 ("area approach"). Another comparison, based on kinetic analysis and simulation, showed that the strength of the respective fluids to dilute the plasma by 20% within 30 min was 0.94, 0.97, 4.44, and 6.15 ("target dilution approach"). Between-subject variability was approximately half as high for the latter approach. Conclusions The relative efficiency of crystalloid infusion fluids differs depending on whether the entire dilution-time profile or only the maximum dilution is compared. Kinetic analysis and simulation is a useful tool for the study of such differences.


2007 ◽  
Vol 57 (2) ◽  
pp. 95-99 ◽  
Author(s):  
James A. Davis ◽  
Ralph Rozenek ◽  
Derek M. DeCicco ◽  
Michael T. Carizzi ◽  
Patrick H. Pham

2009 ◽  
Vol 206 (12) ◽  
pp. 2761-2777 ◽  
Author(s):  
Nebojsa Knezevic ◽  
Mohammad Tauseef ◽  
Tracy Thennes ◽  
Dolly Mehta

The inflammatory mediator thrombin proteolytically activates protease-activated receptor (PAR1) eliciting a transient, but reversible increase in vascular permeability. PAR1-induced dissociation of Gα subunit from heterotrimeric Gq and G12/G13 proteins is known to signal the increase in endothelial permeability. However, the role of released Gβγ is unknown. We now show that impairment of Gβγ function does not affect the permeability increase induced by PAR1, but prevents reannealing of adherens junctions (AJ), thereby persistently elevating endothelial permeability. We observed that in the naive endothelium Gβ1, the predominant Gβ isoform is sequestered by receptor for activated C kinase 1 (RACK1). Thrombin induced dissociation of Gβ1 from RACK1, resulting in Gβ1 interaction with Fyn and focal adhesion kinase (FAK) required for FAK activation. RACK1 depletion triggered Gβ1 activation of FAK and endothelial barrier recovery, whereas Fyn knockdown interrupted with Gβ1-induced barrier recovery indicating RACK1 negatively regulates Gβ1-Fyn signaling. Activated FAK associated with AJ and stimulated AJ reassembly in a Fyn-dependent manner. Fyn deletion prevented FAK activation and augmented lung vascular permeability increase induced by PAR1 agonist. Rescuing FAK activation in fyn−/− mice attenuated the rise in lung vascular permeability. Our results demonstrate that Gβ1-mediated Fyn activation integrates FAK with AJ, preventing persistent endothelial barrier leakiness.


1968 ◽  
Vol 21 (sup103) ◽  
pp. 39-48 ◽  
Author(s):  
J. Siggaard-Andersen ◽  
F. Bonde Petersen ◽  
Thorsten I. Hansen ◽  
K. Mellemgaard

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