EFFECTS OF ERYTHROPOIETIN ON MUSCLE O-2 TRANSPORT DURING EXERCISE IN PATIENTS WITH CHRONIC-RENAL-FAILURE

Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (6RF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as mu ch as the increase in hemoglobin concentration ([Hb]) would predict, W e hypothesized that this discrepancy is due to failure of O-2 transpor t rates to rise in a manner proportional to [Hb], To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- an d post-rHuEPO ([Hb] = 7.5+/-1.0 vs. 12.5+/-1.0 g . dl(-1)) using a sta ndard incremental cycle exercise protocol A group of 12 healthy sedent ary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flo w (Qleg) by thermodilution to obtain O-2 delivery and oxygen uptake (V O2). Despite a 69% increase in [Hb], peak VO2 increased by only 33%, T his could be explained largely by reduced peak leg blood flow, limitin g the gain in O-2 delivery to 37%. At peak VO2, after rHuEPO, O-2 supp ly limitation of maximal VO2 was found to occur, permitting the calcul ation of a value for muscle O-2 conductance from capillary to mitochon dria (DO2), While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects, This kept maximal oxygen ex traction at only 70%, Two important conclusions can be reached from th is study. First, the increase in [Hb] produced by rHuEPO is accompanie d by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restorat ion of [Hb], O-2 conductance from the muscle capillary to the mitochon dria remains considerably below normal.