ULTRAPURE POLYMERIZED BOVINE HEMOGLOBIN (UPPBHB) IMPROVES INTEGRITY OF THE ISOLATED-PERFUSED RAT-KIDNEY (IPRK) - EFFECTS ON FUNCTION AND STRUCTURE

To test the oxyphoretic properties and potential nephrotoxic side-effe cts of polymerized hemoglobin solutions, isolated rat kidneys were per fused in a recirculating system for 180 min. Group I was perfused with a substrate enriched Ringer solution containing hydroxyethylstarch (H ES) to produce isoncotic conditions. In group II HES was substituted i n part by UPPBHb (34 g/l) with a high portion of low molecular weight molecules (= UPPBHb1). In group III 34 g/l of UPPBHb containing an inc reased fraction of high molecular weight polymers (= UPPBHb2) was used . Only UPPBHb2-perfused kidneys showed a reduced renal perfusate flow (RPF, 13.3 +/- 1.1 ml/min g kw), when compared to HES-perfused control s (15.5 +/- 0.8) and UPPBHb1 (15.1 +/- 1.2). Glomerular filtration rat e (GFR) was significantly higher in UPPBHb1-perfused kidneys (902 +/- 107 vs 633 +/- 55 mu l/min g kw for HES). This difference became even more pronounced in the third hour of perfusion (474 +/- 125 vs. 103 +/ - 33). In contrast, UPPBHb2 produced low initial GFR levels of 385 +/- 25, which had only a minor tendency to decline with time. Parallel to GFR, absolute reabsorption of sodium (T-Na) andoxygen consumption (Q( O2)) showed values of 110 +/- 16 and 5.46 +/- 0.33 mu mol/min g kw in UPPBHb1-kidneys vs 83 +/- 6 and 5.09 +/- 0.27 in controls and vs 53 +/ - 4 and 3.66 +/- 0.12 in UPPBHb2-kidneys. Fractional excretion of sodi um (FE(Na)), of potassium (FE(K)), and of water (FE(H2O)) in UPPBHb1 a nd UPPBHb2-perfused kidneys were not significantly different from HES- perfused controls at any time of perfusion. Urinary flow rate (UFR) wa s similar in UPPBHb1- and HES-kidneys. Nevertheless, control kidneys t ended to render oliguric during the third hour of perfusion (UFR 19.9 +/- 4.1 mu l/min g kw), whereas UPPBHb1 preserved urinary flow in a be tter way (83.7 +/- 32.4). UFR of UPPBHb2-kidneys was significantly red uced initially (30.2 +/- 5.1 vs. 105 +/- 33 for HES), but increased st eadily up to 67 +/- 23. In the UPPBHb1 and HES group, all functional p arameters determined declined dramatically within the third hour of pe rfusion, whereas UPPBHb2 produced functional stability. The ill vivo r eaction pattern of renal autoregulation was better preserved in UPPBHb -perfused kidneys than in HES-perfused controls: 74 +/- 6 vs. 59 +/- 5 vs. 42 +/- 4% (of full autoregulatory response) for UPPBHb1, UPPBHb2, and HES kidneys, respectively. Light- and electron microscopic analys is revealed major alterations only for the outer medulla of HES-kidney s. Especially in the inner stripe of the outer medulla (ISOM), which i s the zone of greatest sensitivity to damage in the isolated perfused kidney, severe hydropic degeneration, cell detachment and necrotic des truction of the medullary thick ascending limb (mTAL) was confined to the HES-perfused group, whereas in the UPPBHb1 group mTAL was well pre served. The results suggest that UPPBHb2, although stabilizing the IPR K during prolonged perfusion periods, was not as effective as UPPBHb1 for preserving kidney function in the IPRK-system. UPPBHb1 provided be tter oxygenation than HES perfusion and did not exert detectable nephr otoxic effects on the IPRK.