ULTRAPURE POLYMERIZED BOVINE HEMOGLOBIN IMPROVES STRUCTURAL AND FUNCTIONAL INTEGRITY OF THE ISOLATED-PERFUSED RAT-KIDNEY

Since it became evident that organ dysfunctions after acute hemolysis are nor induced by hemoglobin per se, but by stroma-contaminated hemog lobin, solutions of ultrapure stroma-free hemoglobins were regarded to be possible substitutes for blood in transfusion medicine. We tested one of the recently developed modified bovine hemoglobins (Ultrapure p olymerized bovine hemoglobin 1; UPPBHb1) in the isolated perfused rat kidney (IPRK) model, using a recirculating system. Control kidneys wer e perfused with a substrate-enriched Ringer solution containing hydrox yethyl starch (HES) to produce isoncotic conditions. In the experiment al group HES was substituted in part by UPPBHb1 (34 g/l). For determin ation of functional parameters, the kidneys were perfused for 180 min. A separate set of kidneys of both groups was perfusion fixed after SO min of perfusion which is the period of optimal function. Light and e lectron microscopic analysis revealed major alterations only for the o uter medulla of HES kidneys. Only these suffered from a considerable e xtent of proximal tubular Si damage, exhibiting condensed tubular epit helia. In the inner stripe of the outer medulla, which is the zone of greatest sensitivity to damage in the isolated perfused kidney, severe hydropic degeneration, cell detachment, and necrotic destruction of t he medullary thick ascending limb were seen in the HES-perfused group, too. In the UPPBHb1 group, the medullary thick ascending limb was wel l preserved, and S3 showed only a minor degree of damage. UPPBHB1 kidn eys were further characterized by the occurrence of intracapillary and interstitial precipitates of UPPBHb1 in inner stripe of the outer med ulla and inner medulla. The glomerular filtration rate was significant ly higher in UPPBHb1-perfused kidneys (870+/-50 vs. 630+/-55 mu l/min/ g kidney weight for HES). Absolute reabsorption of sodium paralleled t he behavior of the glomerular filtration rate. The values for renal pe rfusate flow and urinary flow rate did not differ significantly betwee n both groups. Renal autoregulation was better preserved in UPPBHb1-pe rfused kidneys (74+/-6% of full autoregulatory response) than in HES-p erfused controls (42+/-4%). Our results suggest that perfusion of isol ated rat kidneys with UPPBHb1 improves kidney function and morphology, providing better oxygenation than in control kidneys. UPPBHb1 does no t exert additional nephrotoxic effects on the IPRK that will exceed th e noxious potential of the method itself Thus, it must be concluded th at UPPBHb1 may be an oxyphoretic blood substitute with nephroprotectiv e characteristics when compared with nonoxyphoretic substitutes. At le ast, UPPBHb1 seems to be a promising candidate as oxyphoretic additive to perfusates for the IPRK model.