Are i-STAT Results Adversely Affected by an Artificial Blood Substitute In Vivo?

The pattern of BSA-Au uptake in vivo by endothelial cells of the venous sinuses (sinusoidal cells) of rat bone marrow has been described previously. BSA-Au conjugates are taken up exclusively in coated pits and vesicles, enter and pass through an “endosomal” compartment comprised of smooth-membraned tubules and vacuoles and cup-like bodies, and subsequently reside in multivesicular and dense bodies. The process is very rapid, with BSA-Au reaching secondary lysosmes one minute after presentation. (Figure 1)In further investigations of this process an isolated limb perfusion method using an artificial blood substitute, Oxypherol-ET (O-ET; Alpha Therapeutics, Los Angeles, CA) was developed. Under nembutal anesthesia, male Sprague-Dawley rats were laparotomized. The left common iliac artery and vein were ligated and the right iliac artery was cannulated via the aorta with a small vein catheter. Pump tubing, preprimed with oxygenated 0-ET at 37°C, was connected to the cannula.

Download Full-text

Complement activation by artificial blood substitute Fluosol: in vitro and in vivo studies

Transfusion ◽

10.1046/j.1537-2995.1991.31791368343.x ◽

1991 ◽

Vol 31 (7) ◽

pp. 642-647 ◽

Cited By ~ 23

Author(s):

F Hong ◽

KA Shastri ◽

GL Logue ◽

MB Spaulding

Keyword(s):

Complement Activation ◽

Blood Substitute ◽

In Vivo Studies ◽

Artificial Blood

Download Full-text

Increased infection mortality and decreased neutrophil migration due to a component of an artificial blood substitute

Blood ◽

10.1182/blood.v68.2.351.351 ◽

1986 ◽

Vol 68 (2) ◽

pp. 351-354 ◽

Cited By ~ 22

Author(s):

TA Lane ◽

GE Lamkin

Keyword(s):

Animal Model ◽

Host Resistance ◽

Peritoneal Lavage ◽

Neutrophil Migration ◽

Blood Substitute ◽

Reticuloendothelial System ◽

Simultaneous Administration ◽

Artificial Blood ◽

E Coli

Abstract We previously showed that an artificial blood substitute containing perfluorocarbons, Fluosol-DA, inhibited both neutrophil migration and adherence, due to its detergent component, Pluronic F-68. The purpose of the studies we report here was to determine if Fluosol or Pluronic might also reduce in vivo neutrophil migration and impair host resistance to bacterial infection. We studied in vivo PMN migration by injecting mice intraperitoneally (IP) with glycogen, followed by intravenous (IV) infusion of saline, Fluosol, or Pluronic. Peritoneal lavage after eight hours showed a significant decrease in the accumulation of PMN in lavage fluids of animals given either Fluosol or Pluronic (control--.19 +/- .03 X 10(6) PMN/mL, glycogen--1.35 +/- .14; glycogen/Fluosol--0.63 +/- .12; glycogen/Pluronic--0.69 +/- .07). We ascertained the effect of Fluosol and Pluronic on infection mortality by injecting mice IV with saline, Fluosol, or Pluronic, followed by a quantity of E coli (0.6 X 10(7] IP shown in preliminary studies to kill 20% to 50% of the mice in 24 hours. The 24-hour mortality was 14/45- saline, 24/32-Fluosol (chi 2 = 17.1; P less than .001) and 17/23 - Pluronic (chi = 11.2; P less than .001). Neither Fluosol nor Pluronic caused mortality without E coli. The increase in infection mortality occurred when Fluosol was given either two hours before, or simultaneously with E coli, but only with the simultaneous administration of bacteria and Pluronic. Pluronic did not alter reticuloendothelial system (RES) clearance function. These studies indicate that, in an animal model, Fluosol-DA, due to its detergent component Pluronic F-68, impaired neutrophil delivery to an inflammatory locus, and resulted in an increased rate of infection mortality. Since Pluronic did not result in RES blockade, but did impair the delivery of PMN to an inflammatory locus, our results suggest that the latter effect is responsible for the increase in infection mortality.

Download Full-text

Increased infection mortality and decreased neutrophil migration due to a component of an artificial blood substitute

Blood ◽

10.1182/blood.v68.2.351.bloodjournal682351 ◽

1986 ◽

Vol 68 (2) ◽

pp. 351-354

Author(s):

TA Lane ◽

GE Lamkin

Keyword(s):

Animal Model ◽

Host Resistance ◽

Peritoneal Lavage ◽

Neutrophil Migration ◽

Blood Substitute ◽

Reticuloendothelial System ◽

Simultaneous Administration ◽

Artificial Blood ◽

E Coli

We previously showed that an artificial blood substitute containing perfluorocarbons, Fluosol-DA, inhibited both neutrophil migration and adherence, due to its detergent component, Pluronic F-68. The purpose of the studies we report here was to determine if Fluosol or Pluronic might also reduce in vivo neutrophil migration and impair host resistance to bacterial infection. We studied in vivo PMN migration by injecting mice intraperitoneally (IP) with glycogen, followed by intravenous (IV) infusion of saline, Fluosol, or Pluronic. Peritoneal lavage after eight hours showed a significant decrease in the accumulation of PMN in lavage fluids of animals given either Fluosol or Pluronic (control--.19 +/- .03 X 10(6) PMN/mL, glycogen--1.35 +/- .14; glycogen/Fluosol--0.63 +/- .12; glycogen/Pluronic--0.69 +/- .07). We ascertained the effect of Fluosol and Pluronic on infection mortality by injecting mice IV with saline, Fluosol, or Pluronic, followed by a quantity of E coli (0.6 X 10(7] IP shown in preliminary studies to kill 20% to 50% of the mice in 24 hours. The 24-hour mortality was 14/45- saline, 24/32-Fluosol (chi 2 = 17.1; P less than .001) and 17/23 - Pluronic (chi = 11.2; P less than .001). Neither Fluosol nor Pluronic caused mortality without E coli. The increase in infection mortality occurred when Fluosol was given either two hours before, or simultaneously with E coli, but only with the simultaneous administration of bacteria and Pluronic. Pluronic did not alter reticuloendothelial system (RES) clearance function. These studies indicate that, in an animal model, Fluosol-DA, due to its detergent component Pluronic F-68, impaired neutrophil delivery to an inflammatory locus, and resulted in an increased rate of infection mortality. Since Pluronic did not result in RES blockade, but did impair the delivery of PMN to an inflammatory locus, our results suggest that the latter effect is responsible for the increase in infection mortality.

Download Full-text

Activation of plasma complement by perfluorocarbon artificial blood: probable mechanism of adverse pulmonary reactions in treated patients and rationale for corticosteroids prophylaxis

Blood ◽

10.1182/blood.v59.6.1299.1299 ◽

1982 ◽

Vol 59 (6) ◽

pp. 1299-1304 ◽

Cited By ~ 165

Author(s):

GM Vercellotti ◽

DE Hammerschmidt ◽

PR Craddock ◽

HS Jacob

Keyword(s):

Adverse Reactions ◽

Emulsion Stability ◽

Blood Substitutes ◽

Perfluorocarbon Emulsion ◽

Artificial Blood ◽

American Patient ◽

Nonionic Detergent ◽

To Receive

Abstract Perfluorocarbons have shown promise as clinical blood substitutes. Although early experience in Japan with one such product--Fluosol-DA-- has been uncomplicated, we observed an adverse pulmonary reaction in the first American patient to receive it and know of similar reactions in two other Americans so treated. Postulating that activation of plasma complement (C) by the perfluorocarbon emulsion might have caused the reaction, we tested the product to determine if it is an activator of complement. Incubation of Fluosol with plasma led to C3 conversion, decrement in CH50, and generation of C5a-related PMN aggregating activity; EDTA prevented such activation, while EGTA did not, suggesting that it proceeded via the alternative C pathway. Infusion of Fluosol into rabbits produced hypoxemia, neutropenia, thrombocytopenia, and pulmonary leukostasis, mimicking abnormalities previously demonstrated in rabbits receiving infusions of zymosan-activated plasma C. These deleterious responses to Fluosol were diminished by premedicating rabbits with corticosteroids (which had seemed to benefit when used empirically in our patient). In vitro and in vivo, Fluosol's effects were reproduced by Pluronic F-68, the nonionic detergent used to maintain the emulsion stability of Fluosol-DA. We conclude that adverse reactions to Fluosol are probably mediated by C activation and that steroid premedication may prevent them in susceptible patients.

Download Full-text