Renal excretion of pseudo-cross-linked human, porcine and bovine hemoglobins.
The present experiments were done to determine plasma retention, urinary excretion, and acute renal effects of bolus administration (20 mg/100 g), of hemoglobins (human, bovine and porcine) whose tetrameric structure was stabilized by a pseudo-cross-link between the beta-chains. Standard renal clearance studies showed that these preparations had no immediate adverse effects on GFR or ERPF, however, urine flow and electrolyte excretion commonly increased. Plasma disappearance curves best fit a double-exponential and showed components with half-times of 28 +/- 3 and 257 +/- 43 min. A variable fraction, 57 +/- 6%, appeared in the urine, in phase with the early-fast component of plasma disappearance. This in vivo finding of extensive urinary excretion conflicted with sedimentation velocity analysis of these preparations which indicated a homogenous preparation with mean molecular weight of a stable and therefore, unfilterable tetramer. It appears that the glomerular filter selects for permeant species not easily detected by sedimentation velocity analysis. The different species may reflect the presence, within the PXLs of conformational-slow-equilibria among isomeric forms with different degrees of filterability.


CONCLUSIONS
It is important, useful and simple to determine urinary excretion as a means to ascertain molecular stability in vivo.
Urbaitis
B
B
Department of Medicine, Medical School, University of Maryland, Baltimore 21201.
Lu
Y S
YS
Fronticelli
C
C
Bucci
E
E
D000818:Animals; D002417:Cattle; D004573:Electrolytes / Q000652:urine; D006454:Hemoglobins / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics*; D006456:Hemoglobinuria / Q000652:urine; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
D004573:Electrolytes; D006454:Hemoglobins