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Exchange transfusions in rats with a perfluorated blood substitute: effect on thromboxane B2 levels during
Abstract:
The effect of exchange transfusion with the perfluorated blood substitute (Fluosol-43) on endotoxin-induced synthesis of immunoreactive (i) thromboxane (Tx)B2, the stable metabolite of TxA2, was investigated in rats. Fluosol-43 was infused via the femoral vein with matched, incremental blood withdrawal from the carotid artery. Blood was replaced with Fluosol-43 to a final hematocrit of less than 3% in anesthetized rats maintained on 95% O2 and 5% CO2. Circulating platelet counts were reduced from 875 +/- 47 X 10(3)/mm3 in sham controls (N = 21) to 75 +/- 10 X 10(3)/mm3 in Fluosol-43 exchange transfused rats (N2 = 19, P less than 0.001). Circulating leukocytes were decreased from 105 +/- 6.3 X 10(2)/mm2 in sham controls (N = 21) to 17 +/- 1.4 X 10(2)/mm3 in the exchange transfused group (N = 19, P less than 0.001). Immunoreactive (i)TxB2 was measured in plasma or Fluosol-43 obtained from rats prior to and after injection of Salmonella enteritidis endotoxin (20 mg/kg). The iTxB2 levels at 30 minutes after endotoxin increased from 438 +/- 83 pg/ml (N = 4) to 2,895 +/- 663 pg/ml (N = 7) (P less than 0.01) in sham controls. iTxB2 also increased from 242 +/- 23 pg/ml (N = 7) to 2,213 +/- 589 pg/ml (N = 7) in the Fluosol-43 group (P less than 0.002) following endotoxin. The iTxB2 levels also remained significantly elevated (P less than 0.01) in both the sham and the Fluosol-43 groups 2 hours after endotoxin treatment. Endotoxin-stimulated iTxB2 levels at both 30 minutes and 2 hours in sham and Fluosol-43 exchange transfused rats did not vary significantly from each other. Indomethacin pretreatment (2 mg/kg) inhibited the increase in iTxB2 levels by greater than 85% in both groups (P less than 0.004). Blood and Fluosol-43 were taken from sham and exchange transfused rats and incubated ex vivo with the calcium ionophore, A23187 (10 microM). These studies demonstrated that ionophore-stimulated iTxB2 synthesis in the ex vivo Fluosol-43 samples was only 2.6% that of whole blood. Collectively these observations suggest that tissues other than blood components are potential sources of iTxB2 synthesis in endotoxin shock.