CU-2010

Foxhound (weighing 22 to 35 kg)^[1]

0.5 mg/kg; 0.83 mg/kg; 1.25 mg/kg; 1.66 mg/kg

i.v.; slow infusion over 90 minutes

Slightly elevated activated clotting time (ACT) and remarkably elevated activated partial thromboplastin time (aPTT) in all CU-2010 groups compared to control and aprotinin groups.
Prolonged extrinsic system (EXTEM) clotting time (CT) to 58 s (0.5 mg/kg), 86 s (0.83 mg/kg), 82 s (1.25 mg/kg), 51 s (1.66 mg/kg), all P<.05 vs control and aprotinin.
Extended extrinsic system (EXTEM) lysis time (LT) to >3600 s (0.5, 0.83, 1.25 mg/kg) and 3290 s (1.66 mg/kg), with no clot lysis observed within the measurement period for all CU-2010 doses.
Prolonged intrinsic system (INTEM) clotting time (CT) to 845 s (0.5 mg/kg), 1587 s (0.83 mg/kg), 1520 s (1.25 mg/kg), 823 s (1.66 mg/kg), all P<.05 vs control and aprotinin.
Reduced intrinsic system (INTEM) maximum clot strength (MCF) to 41 mm (0.5 mg/kg), 45 mm (0.83 mg/kg), 30 mm (1.25 mg/kg), 47 mm (1.66 mg/kg), all P<.05 vs baseline, with 1.25 mg/kg also P<.05 vs aprotinin.
Preserved coronary blood flow (CBF) at 51 mL/min (0.5 mg/kg), 42 mL/min (0.83 mg/kg), 47 mL/min (1.25 mg/kg), 37 mL/min (1.66 mg/kg), all P<.05 vs control.
Preserved slope of the end-systolic pressure-volume relationship (ESPVR) at 2.32 mm Hg/mL (0.5 mg/kg), 2.81 mm Hg/mL (0.83 mg/kg), 3.57 mm Hg/mL (1.25 mg/kg), 2.96 mm Hg/mL (1.66 mg/kg), with 1.66 mg/kg P<.05 vs control.
Achieved 118% percent recovery of ESPVR at 1.66 mg/kg, P<.05 vs control.
Preserved preload recruitable stroke work (PRSW) at 48 kerg (0.5 mg/kg), 40 kerg (0.83 mg/kg), 55 kerg (1.25 mg/kg), 57 kerg (1.66 mg/kg), with 1.25 and 1.66 mg/kg P<.05 vs aprotinin.
Achieved 108% percent recovery of PRSW at 1.25 mg/kg and 105% at 1.66 mg/kg, both P<.05 vs control and aprotinin.
Preserved coronary endothelial function (vasodilative response to acetylcholine) to levels comparable to aprotinin across all CU-2010 doses, preventing the reduction seen in controls.
Reduced cardiac tissue malonaldehyde (MDA) levels to 2.9 μmol/L/g dry weight (0.5 mg/kg), 3.1 μmol/L/g dry weight (0.83 mg/kg), 2.4 μmol/L/g dry weight (1.25 mg/kg), 1.9 μmol/L/g dry weight (1.66 mg/kg), all P<.05 vs control; 1.66 mg/kg also P<.05 vs aprotinin.