Cell-free hemoglobin preserves renal function during normothermic ischemia

The purpose of this study is to determine whether an infusion of polymerized hemoglobin solution is capable of suppressing the tubular damage and loss of renal function normally seen during a clinically relevant period of warm ischemia.

Male rats (350-450 g) were randomized to treatment with control (5% human serum albumin, HSA, n = 6) or test solution (9% polymerized hemoglobin, PHB, n = 6). Following a right nephrectomy, the left renal artery was perfused with 4 ml of HSA or PHB at 37 degreesC. The left renal artery was temporarily occluded for 50 min. At 72 h, creatinine (Cr), blood urea nitrogen (BUN), and percentage hemoglobin (Hb) were measured and the kidney was removed. Stained kidney sections were graded for ischemic injury (0-4, 0 = normal and 4 = necrosis of the proximal tubule). All results were expressed as means +/- SEM and statistical analysis was performed by t test.

Treatment with PHB resulted in lower Cr (1.2 +/- 0.23 mg/dl vs 3.26 +/- 0.60 mg/dl, P < 0.01) and BUN (60.5 +/- 12.7 mg/dl vs 151 +/- 20.2 mg/dl, P < 0.01) at 72 h compared to HSA controls. Total hemoglobin was not significantly different at 72 h. The weight of all treated kidneys increased; however, the increase was significantly less in the PHB-treated group (34 +/- 9.1% vs 70 +/- 7. 4%, P < 0.01). PHB-treated kidneys had less evidence of histologic damage compared to those in the HSA group (0.75 +/- 0.11 vs 2.50 +/- 0.64, P < 0.05).

During normothermic renal ischemia, renal artery infusion of PHB resulted in preservation of renal function and histologic architecture. PHB solutions may be useful in preserving organ function during prolonged periods of in vivo ischemia.