>> I thought I'd run it by the biofreaks with respect to science while I hunt down the partnership info. <<
Been working on it gradually, in the context of Medinox research..........
Kidney Int 2001 Oct;60(4):1407-14
Effects of enhanced oxygen release from hemoglobin by RSR13 in an acute
renal failure model.
Burke TJ, Malhotra D, Shapiro JI.
Department of Medicine, University of Colorado School of Medicine, Denver, and Integrated
Systems Physiology, Aurora, Colorado; and Departments of Medicine and Pharmacology,
Medical College of Ohio, Toledo, Ohio, USA.
BACKGROUND: Acute renal failure is believed to be caused, in some circumstances, by
impaired oxygen delivery to the outer medulla. This study examined the effect of RSR13, a
synthetic allosteric modifier of hemoglobin oxygen-binding affinity, on renal function in a setting of
acute renal failure in rats. METHODS: An in vivo model of acute renal failure in the rat produced
by reduced renal mass, salt restriction, volume depletion, prostaglandin inhibition, and
radiocontrast administration was used. A computer-based simulation of oxygen tensions along the
nephron was utilized to interpret the findings. Mechanistic studies were subsequently performed
using oxygen-sensitive electrodes and 31P nuclear magnetic resonance (NMR) spectroscopy to
define the effect of RSR13 on renal function in the setting of compromised acute renal failure.
RESULTS: RSR13 did not attenuate acute renal failure in this model; rather, serum creatinine
increased to a greater degree in the RSR13-treated rats than in rats receiving saline vehicle as the
control (P < 0.05). Simulations explained this finding under conditions of severe medullary
hypoxia. Mechanistic studies demonstrated marked worsening of medullary hypoxia following
RSR13 under conditions similar to our experimental model. Furosemide pretreatment to reduce
the imbalance between oxygen supply and demand markedly attenuated the basal-medullary
hypoxia produced in the presence of indomethacin and RSR13 (P < 0.01). Additionally, 31P
NMR studies demonstrated renal adenosine 5'-triphosphate (ATP) depletion in rats with acute
renal failure treated with RSR13 (45% decrease, P < 0.01); again, this effect of RSR13 was
completely prevented by pretreatment with furosemide. CONCLUSIONS: Under conditions of
severe renal medullary hypoxia, induced in part by indomethacin-mediated reductions in outer
medullary blood flow, the administration of RSR13 can exacerbate acute renal dysfunction.
However, reducing the rate of oxygen consumption by inhibiting sodium transport with
furosemide pretreatment or post-treatment appears to be functionally protective. |
