CROSS-LINKED HEMOGLOBIN INCREASES FRACTIONAL REABSORPTION AND GFR IN HYPOXIC ISOLATED-PERFUSED RAT KIDNEYS

We compared the ability of human red blood cells (RBC) and a cell-free oxygen carrier to maintain isolated perfused kidney function under moderately hypoxic conditions. Recirculating perfusate was gassed initially with 93% air-7% CO2, and, after 30 min, the gas was changed to 12 O-2-7 CO2-81% N-2. Oxygen content of the perfusate was increased with RBC (30 g/l Hbg) or highly purified human hemoglobin A(0) (HbA(0)) polymerized with O-raffinose (o-R-poly-Hb, 30 g/l Hbg). For comparison, kidneys were perfused with 60 g/l of bovine serum albumin (BSA) alone. The effects of unmodified hemoglobin were examined by adding 5 g/l of nonpolymerized HbA(0) to the BSA perfusate after 20 min. The effect of increasing oxygen delivery without hemoglobin was examined by switching to 93% O-2 after 20 min during some BSA perfusions (BSA-HiO(2)). Vascular resistance decreased progressively in o-R-poly-Hb- and BSA-HiO(2)-perfused kidneys but remained constant in other experiments. Nitro-L-arginine methyl ester (L-NAME) prevented vasodilation and increased the filtration fraction of o-R-poly-Hb-perfused kidneys with no change in other functions. L-NAME also prevented the formation of methemoglobin. After a 70-min perfusion with BSA, Na reabsorption was 82 +/- 3% (means +/- SD), and inulin clearance [glomerular filtration rate (GFR)] was 0.66 +/- 0.33 ml . min(-1). g(-1). RBC increased reabsorption to 95% (85-98%) (median, 25th-75th percentile) but did not alter GFR (0.52 +/- 0.26 ml . min(-1). g(-1)). o-R-poly-Hb increased Na reabsorption proportionately more than GFR, so that, while GFR was doubled to 1.04 +/- 0.40 ml . min(-1). g(-1), Na reabsorption increased to 98% (92-99.5%). HbA(0) increased GFR to 1.07 +/- 0.44 ml . min(-1). g(-1) and increased reabsorption to 89 +/- 6%. A similar increase in Na reabsorption (93 +/- 2%) and GFR (1.38 +/- 0.3 ml . min(-1). g(-1)) was produced by increasing O-2 content of BSA with 93% O-2 o-R-poly-Hb was most effective in raising and maintaining overall renal function and lowering urine Na concentration and protein excretion.