title: Cross-linked hemoglobin increases fractional reabsorption and GFR in hypoxic isolated perfused rat kidneys.
abstract: 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 O2-7 CO2-81% N2. Oxygen content of the perfusate was increased with RBC (30 g/l Hbg) or highly purified human hemoglobin Ao (HbAo) 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 HbAo to the BSA perfusate after 20 min. The effect of increasing oxygen delivery without hemoglobin was examined by switching to 93% O2 after 20 min during some BSA perfusions (BSA-HiO2). Vascular resistance decreased progressively in o-R-poly-Hb- and BSA-HiO2-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%). HbAo increased GFR to 1.07 +/- 0.44 ml.min-1.g-1 and increased reabsorption to 89 +/- 6%.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Clinical Biochemistry, University of Toronto, Ontario, Canada.
authors.forename: A D
authors.initials: AD
authors.lastname: Baines
authors.forename: B
authors.initials: B
authors.lastname: Christoff
authors.forename: D
authors.initials: D
authors.lastname: Wicks
authors.forename: D
authors.initials: D
authors.lastname: Wiffen
authors.forename: D
authors.initials: D
authors.lastname: Pliura
mesh_terms: D000042:Absorption / Q000187:drug effects; D000818:Animals; D004912:Erythrocytes / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D011507:Proteinuria / Q000652:urine; D011887:Raffinose / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006454:Hemoglobins; C097124:O-raffinose cross-linked human hemoglobin; D010710:Phosphates; D011887:Raffinose