Renal Tissue PO 2 Sensing During Acute Hemodilution is Dependent on the Diluent.

The mechanism by which the kidney senses changes in hemoglobin concentration (Hb) may inform decisions regarding the optimal fluid for intravascular volume resuscitation in critical care settings where starch solution may be nephrotoxic. We hypothesized that hemodilution with starch solutions would reduce renal P kt O 2 to a more severe degree than other diluents. Anesthetized Sprague Dawley rats (n=61) were block-randomized to undergo hemodilution with either colloid (6% hydroxyethyl starch or 5% albumin), crystalloid (saline), or a sham procedure (control) (n=6-12 rats/group). We measured mean arterial pressure (MAP), arterial blood gases, Hb (cooximetry), cardiac output (CO, echocardiography), renal P kt O 2 and hypoxic gene expression (mRNA qRT-PCR). Following hemodilution, MAP decreased in the saline group while Hb and blood oxygen content (C a O 2 ) decreased in all groups. Cardiac output increased (~50%) after colloid, but not after saline hemodilution. Renal P kt O 2 decreased in proportion to the reduction in Hb in all treatment groups. At comparably reduced Hb and P a O 2 values, hemodilution with starch resulted in a larger decrease in kidney P kt O 2 relative to animals hemodiluted with albumin or saline (p<0.008). Renal erythropoietin (EPO) mRNA levels increased after hemodilution in all groups, but other HIF-dependent molecules did not increase (Glut-1, GAPDH, VEGF). This suggests that EPO expression is highly responsive to changes in C a O 2 and demonstrates the capacity for the kidney as a biosensor of C a O 2 . Our data demonstrates that P kt O 2 reflects proportional changes in C a O 2 and supports the hypothesis that hemodilution with starch colloid solution impairs renal P kt O 2 , relative to hemodilution with albumin and saline.