Bovine hemoglobin. HBOC-201 causes a reduction of the oxygen partial pressure in poststenotic skeletal muscle

Abstract

We investigated the effects of ultrapurified polymerized bovine hemoglobin (HBOC-201) on skeletal muscle tissue oxygen tension when applied before establishment of a nearly complete arterial stenosis. Twelve foxhounds were anaesthetized IV and mechanically ventilated with 30% oxygen in air. Catheters were inserted into the right femoral artery and vein for measurements of haemodynamic parameters and blood-gas sampling. Arterial blood flow of the left popliteal artery was measured by an electromagnetic flow probe. Skeletal muscle tissue oxygen tension (tpo2) was measured in the left gastrocnemic muscle using a stepwise-driven polarographic needle probe, creating histograms from 200 single tpO2 measurements. Following isovolaemic haemodilution with Ringer's solution to a target haematocrit of 20%, the animals were randomly assigned to receive either 200 ml of predonated fresh blood (group 1) or 200 ml of HBOC-201 (MW 32,000-500,000; Hb 13 +/- 1 g-dl-1, group 2). After a 15-min stabilization period, a 95% artificial stenosis of the left popliteal artery was established. While animals of group 1 received two applications of 200 ml 6% hetastarch (HES, 200,000; 0.5), animals of group 2 received 200 ml Ringer's solution 45 and 75 min after establishment of the arterial stenosis, respectively. Variables were measured at baseline, after haemodilution and application of the respective compound, and 30, 60 and 90 min after establishment of the stenosis. Demographic data, muscle temperature and arterial blood gases did not differ between groups. With the exception of a higher mean pulmonary artery pressure in HBOC-201-treated animals, haemodynamics did not differ between groups. In both groups oxygen delivery and oxygen consumption of the muscle decreased in parallel to the decreasing blood flow during arterial stenosis. In contrast, oxygen extraction ratio increased after infusion of HBOC-201 and remained unchanged during stenosis (P < 0.05). In group 1, the tpO2 decreased during stenosis when compared to baseline (P < 0.001) and remained decreased after administration of HES. In contrast, administration of 200 ml of HBOC-201 before establishment of the arterial stenosis sustained the tpO2 values at nearly baseline levels during stenosis. Skeletal muscle tissue oxygen tension was higher after HBOC-201 infusion during stenosis when compared to HES infusion (P < 0.001). These data suggest that haemoglobin solutions can reach poststenotic tissues. The increased oxygen extraction after application of HBOC-201 is associated with improved skeletal muscle oxygen tension during severe arterial stenosis.