Effects of hemoglobin-based oxygen-carrying solutions in anesthetized rats with acute ischemic renal failure.
The effects of three hemoglobin solutions were compared with those of iso-oncotic human serum albumin in rats with ischemic renal failure and sham-operated controls. Unmodified and alpha-alpha cross-linked hemoglobins both increase mean arterial pressure and systemic vascular resistance and reduce cardiac output substantially and to a comparable extent. In contrast, omicron-raffinose cross-linked hemoglobin has no deleterious effect on any of these parameters. In sham-operated rats unmodified hemoglobin reduces the glomerular filtration rate (GFR) by approximately 30%, whereas neither of the two cross-linked hemoglobins has any adverse effect on GFR in this group. None of the three hemoglobin solutions exacerbated the degree to which GFR was reduced by ischemia-reperfusion injury. Also, the degree of tubular necrosis induced by ischemia-reperfusion injury was also comparable in all groups. We conclude the following: (1) omicron-raffinose cross-linking, but not alpha-alpha cross-linking, ameliorates the effects of unmodified hemoglobin on vascular resistance and cardiac output; (2) both forms of cross-linking reduce the nephrotoxicity exhibited by unmodified hemoglobin in sham-operated rats; and (3) none of the hemoglobin solutions exacerbate renal injury induced by ischemia-reperfusion.
Lieberthal
W
W
Renal and Pathology Divisions, and the Naval Blood Research Laboratory, Boston University Medical Center, Massachusetts, USA.
Fuhro
R
R
Andry
C
C
Valeri
C R
CR
D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism*; D011887:Raffinose / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012709:Serum Albumin / Q000494:pharmacology; D012964:Sodium / Q000652:urine; D014661:Vasoconstriction / Q000187:drug effects*
D006454:Hemoglobins; C097124:O-raffinose cross-linked human hemoglobin; D012709:Serum Albumin; C053936:hemoglobin XL99alpha; D012964:Sodium; D011887:Raffinose; D001241:Aspirin; D010100:Oxygen