Plasma clearance of 5-FU and IrC™ administered as single agents or co-administered.

<p>Mice were injected i.v. with radio-labeled 5-FU (40 mg/kg) or IrC™ (40 mg IRI/kg), or both agents simultaneously. At various time points post-injection, the plasma concentrations of 5-FU and IRI (lactone) were determined. A) Mean plasma concentration of 5-FU +/− standard deviation (n = 4) after administration alone (solid gray line) or after co-administration with IrC™ (solid black line). B) Mean plasma concentration of IRI lactone +/− standard deviation (n = 4) after administration of IrC™ alone (dashed gray line) or after co-administration of IrC™ with 5-FU (solid black line).</p

Exposure time dependency of IRI and/or 5-FU cytotoxicity <i>in vitro</i>.

<p>A–D) Single agent exposure time dependency. LS174T (A and B) and HT-29 (C and D) cells were exposed to IRI (A and C) or 5-FU (B and D) for 1 (•, dotted line), 4 (<b>□</b>, solid line), 8 (▾, dotted line) 24 (<b>⋄</b>, solid line), 48 (<b>X</b>, dotted line), or 72 h (○, solid line). E) Combination exposure time dependency. HT-29 cells were exposed to IRI/5-FU (1∶1 molar ratio) for 1 h (•), 8 h (▾), or 48 h (<b>X</b>). F) Calculated CI values at FA = 0.9 for HT-29 cells exposed to IRI/5-FU (1∶1 molar ratio) for 1–72 h. A–D) Each point represents the mean +/− standard deviation (n = 3–9) from 2–3 experiments, each completed in triplicate. E, F) Each point or bar represents a combination index value calculated from cytotoxicity data compiled from 2–4 separate experiments, each completed in triplicate. CI of 0.8 to 1.2 suggests additive interactions; CI <0.8 suggests synergistic interactions; and CI >1.2 suggests antagonistic interactions.</p

Efficacy of IRI/5-FU and IrC™/5-FU treatment in the HT-29 s.c. model of CRC.

<p>Mice bearing s.c. HT-29 tumors were treated with saline+D5W (grey solid square), 5-FU (16 mg/kg; black solid upright triangle), IRI (60 mg/kg; grey solid diamond), IrC™ (40 or 60 mg IRI/kg; black solid inverted triangle or black solid circle, respectively), IRI +5-FU (60 mg/kg +16 mg/kg; black open circle), or IrC™ +5-FU (40 mg IRI/kg +16 mg/kg; grey solid star). Beginning on day 14, D5W and 5-FU were administered QD×5 (x 3 weeks) via i.p. injection (arrowheads); all other treatments were administered Q7D×3 via i.v. injection (full arrows). Data are presented as mean fold tumor volume increase +/− standard error of the mean (n = 6).</p

Concentrations of argon gas (µl/ml) in blood in home cage controls, animals ventilated under normoxic conditions, animals ventilated with argon after hypoxia, and animals ventilated with argon after hypoxia that subsequently underwent hypothermia.

<p>Separate animals within one experimental setup are displayed with different symbols (open circles and closed squares).</p

Schematic representation of the three steps of the experimental setup.

<p>Schematic representation of the three steps of the experimental setup.</p

Schematic of ventilator setup.

<p>Schematic of ventilator setup.</p

Coefficients of argon, hypoxia and hypothermia after multivariable analysis of mean arterial blood pressure (MABP), heart rate, aEEG voltage and regional cerebral saturation (rScO₂).

<p>Coefficients of argon, hypoxia and hypothermia after multivariable analysis of mean arterial blood pressure (MABP), heart rate, aEEG voltage and regional cerebral saturation (rScO₂).</p

Calculated differences in monitored parameters (normoventilation – argon ventilation) displayed as absolute difference.

<p>For reference, the median value of the 6 animals during baseline is added to the right of each panel. Each dot represents a single switch from argon to normoventilation or vice versa. Ag: argon, HI: hypoxia-ischemia, HT: hypothermia.</p

Recorded physiological data from representative animal receiving therapeutic hypothermia.

<p>Black horizontal bars represent periods of argon ventilation.</p