Each catheter was fixed

with a surgical suture. At the end of experiment, animals were sacrificed by resection of the heart, liver, spleen, lung, kidney, brain, M. gastrocnemius and small intestine under deep isoflurane anesthesia. In the main setting we compared three experimental groups. One group (n = 14) received PFD-filled PLGA microcapsules (1.5 µm), one group (n = 9) was medicated with a sterile solution of 0.25% PVA (maximum possible concentration of PVA remainder from capsule synthesis) and one group (n = 9) was treated with 0.9% NaCl. All solutions were infused continuously for 30 min into the right femoral vein using a syringe pump (20 ml/kg body weight × h). The total volume of 20 ml/kg body weight was chosen, because this is a typical volume (5–30 ml/kg body weight) for studies with oxygen carriers [ 2, 14]. The short infusion Ulixertinib cell line time of 30 min was selected as pre-hospital treatment of trauma or other severely injured patients (the potential target population for artificial oxygen carriers) should not exceed 30–40 min [ 15, 16]. After the stop check details of infusion, 12 animals were monitored for 4 h. As high blood volumes were required for determination of cytokines and complement factors, for 20 animals the main setting was shortened from 270 to 150 min and 90 min, respectively (NaCl and PVA each n = 3

and PFD-filled PLGA microcapsules 1.5 µm n = 4 for both time points). The frozen section procedure (see below) was performed in an additional setting only slightly differing from the main setting (see section frozen section procedure) with 2 groups, one receiving 1 µm PFD-filled PLGA microcapsules (n = 2) and 5-FU mw one receiving 1.5 µm PFD-filled PLGA microcapsules (n = 2). For the assessment

of hepatic microcirculation, in vivo microscopy (intravital microscopy, IVM) was performed in an extra, independent setting (see section in vivo microscopy) with 4 groups: PFD-filled PLGA microcapsules (1 and 1.5 µm), PLGA microspheres (1.5 µm) and 0.9% NaCl each n = 6. Systolic blood pressure, diastolic blood pressure and mean arterial blood pressure (MAP) were recorded continuously via the femoral artery catheter that was connected to a pressure transducer and displayed on a monitor. Ringer solution was delivered at 3 ml/h to keep the catheter functional. Heart rates were determined from systolic blood pressure spikes. The breathing rate was determined by counting the ventilation movements per minute every 10 min. The core body temperature of the rats was continuously monitored using a rectal sensor; cooling below 37 °C was prevented by both an underlying thermostat-controlled operating table and by covering the animals with aluminum foil. Blood samples (0.5 ml) for both blood gas analysis and the monitoring of released enzymes activities in plasma in the main setting (see study groups) were taken from the femoral artery catheter before the start of infusion (after catheterization of A.