Effects of rhu-erythropoietin (rhu-EPO) or SCFA derivatives on hemoglobin and hematocrit in chronically anemic baboons that underwent phlebotomy.

Duration of the ongoing phlebotomy is designated by the horizontal bar above each graph. Compound administration is shown by open horizontal bars. In all figure panels: total hemoglobin levels are shown by ●; hematocrit levels, ○. (A) Phlebotomy of 3.5 mL/kg per day was performed in baboon 497, designated by the closed bar above the graph. Administration of rhu-EPO (300 U/kg 3 times per week) is shown by the open bars. During treatment, hemoglobin and hematocrit levels remained stable, despite the ongoing phlebotomy. When rhu-EPO was withdrawn and phlebotomy continued, hemoglobin levels declined by 1.0 g/dL over 5 days. (B) Effects of α methyl hydrocinnamic acid (50 mg/kg per day intravenously for 5 days a week over 3 weeks) administered to the same animal shown in panel A (baboon 497). The baboon underwent similar phlebotomy (3.5 mL/kg per day; shown by the closed horizontal bar). Treatment with α methyl hydrocinnamic acid (open horizontal bars) induced an increase in total hemoglobin level of 2.5 g/dL and an absolute increase in hematocrit level of 7 percentage points (28% of baseline), despite the ongoing daily phlebotomy. (C) Effects of α methyl hydrocinnamic acid in another baboon 196. Daily phlebotomy alone (13 mL/kg per week) resulted in declines in total levels of hemoglobin and hematocrit. Administration of the SCFAD (200 mg/kg per day intravenously) was begun on day 8, shown by the open bars, followed by an increase in total hemoglobin level of 3 g/dL and in hematocrit level of 8 absolute percentage points (40% above baseline). When the phlebotomy was increased further to 21 mL/kg per week on day 14, hemoglobin and hematocrit levels remained stable. (D) Effects of rhu-EPO administered to baboon 894 with a daily phlebotomy of 7 mL/kg per day, shown by the closed horizontal bar. Despite the administration of rhu-EPO (300 U/kg daily [as shown by the open horizontal bars]), a decline in hemoglobin and hematocrit levels occurred with this substantial phlebotomy. (E) Effects of the SCFAD phenoxyacetic acid in the baboon 894, shown in panel D. Daily phlebotomy is designated by the closed horizontal bar. Four doses of phenoxyacetic acid were administered orally (700-900 mg/kg) on alternate days (designated by the open bars) over 2 weeks. An increase in hemoglobin level of 2.4 g/dL and an increase in hematocrit level of 7 absolute percentage points (30% above baseline) were observed. (F) Effects of sodium 2,2 dimethyl butyrate in baboon 1997 administered intravenously (700 mg/kg) 5 days a week for 6 weeks (open bars). Chronic phlebotomy (6.3 mL/kg per day) is designated by the closed bar. An increase in hemoglobin level of 2.0 g/dL and an increase in hematocrit level of 6 percentage points were observed. When the phlebotomy was increased to 7.4 mL/kg per day on day 20, there was no significant further increase, but hemoglobin and hematocrit levels remained stable.