Tissue-specific extravasation of albumin-bound Evans blue in hypothermic and rewarmed rats

2002 ◽  
Vol 80 (3) ◽  
pp. 233-243 ◽  
Author(s):  
Candace B Matthew ◽  
Ingrid V Sils ◽  
Amy M Bastille
Keyword(s):  
Blood Flow ◽  
Vascular Permeability ◽  
Evans Blue ◽  
Gastrocnemius Muscle ◽  
Endothelial Permeability ◽  
Specific Flow ◽  
Flow Rates ◽  
Decrease Blood Flow ◽  
Organ Specific ◽  
Endothelial Integrity

The effects of hypothermia and rewarming on endothelial integrity were examined in intestines, kidney, heart, gastrocnemius muscle, liver, spleen, and brain by measuring albumin-bound Evans blue loss from the vasculature. Ten groups of twelve rats, normothermic with no pentobarbital, normothermic sampled at 2, 3, or 4 h after pentobarbital, hypothermic to 20, 25, or 30°C, and rewarmed from 20, 25, or 30°C, were cooled in copper coils through which water circulated. Hypothermic rats were cooled to the desired core temperature and maintained there for 1 h; rewarmed rats were cooled to the same core temperatures, maintained there for 1 h, and then rewarmed. Following Evans blue administration, animals were euthanized with methoxyflurane, tissues removed, and Evans blue extracted. Because hypothermia and rewarming significantly decrease blood flow, organ-specific flow rates for hypothermic and rewarmed tissues were used to predict extravasation. Hypothermia decreased extravasation in tissues with continuous endothelium (brain, muscle) and increased it in tissues with discontinuous endothelium (liver, lung, spleen). All tissues exhibited significant (p < 0.05) differences from normothermic controls. These differences are attributed to a combination of anesthesia, flow, and (or) change in endothelial permeability, suggesting that appropriate choice of organ and temperature would facilitate testing pharmacological means of promoting return to normal perfusion.Key words: hypothermia, rewarming, vascular permeability, Evans blue, endothelium, anesthesia, thermoregulation.

Modelling radioimmunotherapy with anti-CD45 antibody to obtain a more favourable biodistribution

2009 ◽  
Vol 48 (03) ◽  
pp. 113-119 ◽  
Author(s):  
F. J. Király ◽  
P. Kletting ◽  
S. N. Reske ◽  
G. Glatting
Keyword(s):  
Blood Flow ◽  
Antigen Expression ◽  
Tissue Blood Flow ◽  
Dose Ratio ◽  
Specific Flow ◽  
Blood Flows ◽  
Optimal Delay ◽  
Organ Specific ◽  
Specific Antigens ◽  
Reaction Constants

SummaryRadioimmunotherapy (RIT) is a method to selectively deliver radiation to malignant haemato logical cells by addressing specific antigens. One approach to improve the bio-distribution is to administer a preload of unlabelled antibodies. The aim of this study was to develop a model, which describes distribution of labelled and unlabelled antibodies based on the tissue blood flow and the competing binding behaviour of the antibodies. Such a model can be used to improve biodistribution in the particular case of RIT using anti-CD45 antibodies. Methods: A compartmental model for the interconnected organs was developed. Reaction constants and organ specific flow, antigen concentrations and distribution volumes were taken from the literature. The organ residence times were calculated for different amounts of given labelled and unlabelled antibodies and the time delay between their administrations. Results: The model is capable to describe the preloading effect. The biodistribution of labelled or unlabelled antibodies depends essentially on the specific blood flow to the organ and its antigen expression. The dose ratio of bone marrow to liver is maximized by applying sufficient unlabelled monoclonal antibody (mAb) to saturate antibody binding in the competing organs and by applying the labelled mAb with a delay of more than one hour. Conclusions: The developed model qualitatively describes how a preload can considerably increase selectivity of RIT due to different blood flows and antigen distribution in relevant organs. In addition, simulations can identify the optimal delay between the application of labelled and unlabelled antibody. For future analyses, i.e., to fit patient data, degradation and excretion should be incorporated into the model.

Microcirculatory changes in sodium taurocholate-induced pancreatitis in rats

1991 ◽  
Vol 260 (2) ◽  
pp. G346-G351 ◽  
Author(s):  
K. Kusterer ◽  
M. Enghofer ◽  
S. Zendler ◽  
C. Blochle ◽  
K. H. Usadel
Keyword(s):  
Acute Pancreatitis ◽  
Blood Flow ◽  
Vascular Permeability ◽  
Sodium Taurocholate ◽  
Image Analyzer ◽  
In Vivo Microscopy ◽  
Microscopy Technique ◽  
Permeability Changes ◽  
Hemorrhagic Necrosis

Using an in vivo microscopy technique, we studied the microcirculatory changes in sodium taurocholate-induced pancreatitis in rats. With a computerized image analyzer system, blood flow, vascular permeability changes, and capillary densities were measured. Intraductal infusion of 0.4 ml saline had only minor effects on the microcirculation. Various concentrations and volumes of sodium taurocholate solutions were infused into the pancreatic duct. Sodium taurocholate (0.4 ml, 4%) led to increased vascular permeability preceding stasis within 232 +/- 47 s, followed by hemorrhagic necrosis in the head of the pancreas. In the corpus close to the tail of the pancreas capillary blood flow was maintained. In conclusion, this study shows that the microcirculation of the pancreas can be excellently investigated with in vivo microscopy. With this method, tremendous distribution disturbances of the microcirculation in the pancreas can be seen in the course of acute pancreatitis. Vascular permeability changes and stasis of the microcirculation represent the primary microcirculatory events in acute pancreatitis induced by sodium taurocholate in the areas where hemorrhagic necrosis occurs.

The Effect of Hematocrit on the Clearance of Small Molecules during Hemodialysis

1983 ◽  
Vol 6 (3) ◽  
pp. 127-130 ◽  
Author(s):  
C. Woffindin ◽  
N.A. Hoenich ◽  
D.N.S. Kerr
Keyword(s):  
Blood Flow ◽  
Regression Analysis ◽  
Small Molecules ◽  
Flat Plate ◽  
Flow Rate ◽  
Distribution Curve ◽  
Blood Flow Rate ◽  
Hollow Fibre ◽  
Urea Clearance ◽  
Flow Rates

Data collected during the evaluation of a series of hemodialysers were analysed to see the effect of hematocrit on the clearance of urea and creatinine. All evaluations were performed on patients with a range of hematocrits with a mean close to 20%. The urea clearance of those in the upper half of the distribution curve (mean hematocrit 29.4%) was not significantly different from that of patients in the lower half of the distribution curve (mean hematocrit 16.9%) whether the clearance was studied at high or low blood flow rates and with hollow fibre or flat plate disposable hemodialysers. Likewise, there was no correlation between hematocrit and urea clearance by regression analysis. In contrast, the clearance of creatinine was affected by hematocrit being greater at lower hematocrit values. This difference was independent of blood flow rate and dialyser type and was confirmed by regression analysis.

Derecruitment of filtration surface area in paraquat-injured isolated dog lungs

1990 ◽  
Vol 68 (4) ◽  
pp. 1581-1589 ◽  
Author(s):  
T. Shibamoto ◽  
J. C. Parker ◽  
A. E. Taylor ◽  
M. I. Townsley
Keyword(s):  
Blood Flow ◽  
Surface Area ◽  
Vascular Resistance ◽  
High Flow ◽  
Base Line ◽  
Flow Rates ◽  
Blood Flows ◽  
Capillary Filtration Coefficient ◽  
Specific Index ◽  
Filtration Surface

The capillary filtration coefficient (Kf,c) is a sensitive and specific index of vascular permeability if surface area remains constant, but derecruitment might affect Kf,c in severely damaged lungs with high vascular resistance. We studied the effect of high and low blood flow rates on Kf,c in papaverine-pretreated blood-perfused isolated dog lungs perfused under zone 3 conditions with and without paraquat (PQ, 10(-2) M). Three Kf,cs were measured successively at hourly intervals for 5 h. These progressed sequentially from isogravimetric blood flow with low vascular pressure (I/L) to high flow with low vascular pressure (H/L) to high flow with high vascular pressure (H/H). The blood flows of H/L and H/H were greater than or equal to 1.5 times that of I/L. There were no significant changes in Kf,c in lungs without paraquat over a 50-fold range of blood flow rates. At 3 h after PQ, I/L-Kf,c was significantly increased and both isogravimetric capillary pressure and total protein reflection coefficient were decreased from base line. At 4 and 5 h, H/L-Kf,c was significantly greater than the corresponding I/L-Kf,c (1.01 +/- 0.22 vs. 0.69 +/- 0.09 and 1.26 +/- 0.19 vs. 0.79 +/- 0.10 ml.min-1.cmH2O-1.100 g-1, respectively) and isogravimetric blood flow decreased to 32.0 and 12.0% of base line, respectively. Pulmonary vascular resistance increased to 12 times base line at 5 h after PQ. We conclude that Kf,c is independent of blood flow in uninjured lungs. However, Kf,c measured at isogravimetric blood flow underestimated the degree of increase in Kf,c in severely damaged and edematous lungs because of a high vascular resistance and derecruitment of filtering surface area.

Relation of blood flow to VO2, PO2, and PCO2 in dog gastrocnemius muscle

1988 ◽  
Vol 255 (5) ◽  
pp. H1004-H1010 ◽  
Author(s):  
D. E. Mohrman ◽  
R. R. Regal
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Gastrocnemius Muscle ◽  
Muscle Blood Flow ◽  
Carbon Dioxide Tension ◽  
Experimental Conditions ◽  
Muscle Oxygen ◽  
Muscle Oxygen Consumption ◽  
Relationship Of ◽  
The Relationship

We pump-perfused gastrocnemius-plantaris muscle preparations at constant pressure to study the relationship of muscle blood flow (Q) to muscle oxygen consumption (VO2), venous oxygen tension (PVO2), and venous carbon dioxide tension (PVCO2) during steady-state exercise at different rates. Tests were performed under four experimental conditions produced by altering the perfusate blood-gas status with a membrane lung. The consistency of the relationship of Q to other variables was evaluated by statistical analysis of fitted curves. Not one of the above listed variables had the same relationship with Q in all four of the experimental conditions we tested. However, we did find that a consistent relationship existed among Q, PVO2, and PVCO2 in our data. That relationship is well described by the equation (Q-23).[PVO2 - (0.5.PVCO2) - 3] = 105 (when Q is expressed in ml.100 g-1.min-1 and PVO2 and PVCO2 in mmHg). One interpretation of this result is that both PO2 and PCO2 are important variables in the control of blood flow in skeletal muscle the combined influence of which could account for nearly all of the hyperemia response to steady-state muscle exercise.

scholarly journals The G protein βγ subunit mediates reannealing of adherens junctions to reverse endothelial permeability increase by thrombin

2009 ◽  
Vol 206 (12) ◽  
pp. 2761-2777 ◽  
Author(s):  
Nebojsa Knezevic ◽  
Mohammad Tauseef ◽  
Tracy Thennes ◽  
Dolly Mehta
Keyword(s):  
Vascular Permeability ◽  
Focal Adhesion ◽  
Inflammatory Mediator ◽  
Adherens Junctions ◽  
Endothelial Permeability ◽  
Endothelial Barrier ◽  
Dependent Manner ◽  
Permeability Increase ◽  
Lung Vascular Permeability

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.

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