Cellular bioenergetics after erythropoietin therapy in chronic renal failure.

摘要: After erythropoietin (rHuEPO) therapy, patients with chronic renal failure (CRF) do not improve peak O2 uptake (VO2 peak) as much expected from the rise in hemoglobin concentration ([Hb]). In a companion study, we explain this phenomenon by concurrent effects of fall muscle blood flow after rHuEPO and abnormal capillary conductance observed CRF patients. The latter is likely associated poor microcirculatory network capillary-myofiber dissociation due to uremic myopathy. Herein, cellular bioenergetics its relationships transport, before were examined eight (27 +/- 7.3 [SD] yr) studied pre- post-rHuEPO ([Hb] = 7.8 0.7 vs. 11.7 g x dl-1) during an incremental cycling exercise protocol. Eight healthy sedentary subjects (26 3.1 served controls. We hypothesize that myopathy provokes cytosolic dysfunction but mitochondrial oxidative capacity abnormal. 31P-nuclear magnetic resonance spectra (31P-MRS) vastus medialis obtained throughout protocol consisting periods 2 min (at 1.67 Hz) at increasing work-loads interspersed resting 2.5 min. On different day, identical protocol, arterial femoral venous gas data together simultaneous measurements (Qleg) calculate delivery (QO2leg) (VO2leg). Baseline [phosphocreatine] [inorganic phosphate] ratio ([PCr]/[Pi]) did change (8.9 1.2 8.8 1.2, respectively), it was significantly lower than controls (10.9 1.5) (P 0.01 each). At given submaximal or VO2leg, no seen on ([PCr]/[Pi] ratio, %[PCr] consumption halftime [PCr] recovery exercise), nor intracellular pH (pHi). bioenergetic status pHi, below those control group. However, differences 31P-MRS detected between rHuEPO, VO2, Qleg fell 20% < 0.04), limiting QO2leg 17%, value reach statistical significance. corresponding extraction decreased 73 4% 68 8.2% 0.03). These changes indicate maximal microcirculation mitochondria increase despite 50% [Hb] how VO2leg rHuEPO. Differences possibly lactate differences, post-rHeEPO appear be key factor cell