The purpose of this study was to determine the effect of the hemoglobin based @entity26 carrier, @entity968 conjugated @entity291 hemoglobin ( @entity970 -Hb) on the physiology of the @entity35 . This study was divided into the following 3 parts: pharmacokinetics, cardiovascular, and histopathology. Pharmacokinetic studies evaluated the @entity970 -Hb circulatory life and the resultant effect on urine composition. Telemetric intravascular blood pressure probes monitored the heart rate and mean arterial pressure. Renal arterial blood flow was determined by intraoperative perivascular ultrasound. Tissue histology was evaluated for both time and model dependent responses. The mean circulatory half-life of @entity970 -Hb was 17.7+/-0.3 h. @entity644 and @entity8763 were greatly reduced with @entity970 conjugation. @entity970 -Hb treated @entity35 produced 8.5 times and 49 times less @entity644 and @entity8763 , respectively, than unmodified @entity291 Hb treated animals. The mean arterial pressure (MAP) in @entity970 -Hb treated @entity35 was insignificantly different from sham controls undergoing a 30% exchange transfusion while dextran caused an initial reduction and @entity291 Hb produced a prolonged elevation in the MAP. In these same anesthetized @entity35 , @entity970 -Hb slightly decreased the heart rate while dextran caused an increase and @entity291 Hb had no effect. In addition, @entity70017 was able to maintain the renal arterial blood flow while both Ringer's lactate and @entity291 Hb caused a reduction in the blood flow. Finally, @entity970 -Hb treated @entity35 showed a dose and time dependent formation of vacuoles within the renal proximal convoluted tubules and splenic macrophages in both top-load and exchange transfusion models, but no other morphological changes. In conclusion, @entity970 -Hb had a relatively long vascular persistence that did not cause any significant alterations in the urinalysis, cardiovascular function, or tissue histopathology in the @entity35 .

Effect of @entity968 conjugated XXXX hemoglobin in both top-load and exchange transfusion @entity35 models.

@entity644 :: ('MESH:D011507', 'Disease') :: ['proteinuria', 'Proteinuria'] @entity70017 :: ('MESH:C109960', 'Chemical') :: ['PEG-Hb'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity8763 :: ('MESH:D006456', 'Disease') :: ['hemoglobinuria'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity291 :: ('9913', 'Species') :: ['bovine'] @entity970 :: ('CHEBI:46793', 'Chemical') :: ['PEG'] @entity968 :: ('MESH:D011092', 'Chemical') :: ['polyethylene glycol']
@entity291 :: (9913,Species) :: ['bovine']
