title: Reduced cerebral blood flow but elevated cerebral glucose metabolic rate in erythropoietin overexpressing transgenic mice with excessive erythrocytosis.
abstract: To examine the impact of excessive erythrocytosis on local cerebral blood flow (CBF) and cerebral glucose metabolic rate (CMR(glc)), we made use of our constitutively erythropoietin (Epo)-overexpressing transgenic mouse line (tg-6) that reach a mean hematocrit of 0.87. Compared with wild-type (wt) control siblings, CBF decreased by 44% in tg-6 mice, while upon hemodilution (tg-6-HD) to a physiologic hematocrit (e.g., 0.44) tg-6-HD mice returned the CBF to wt levels. Cerebral blood flow was determined in another transgenic mouse line that overexpresses human Epo in the brain only (tg-21): CBF increased by 17% compared with wt controls. However, oxygen delivery was similar in all four mouse groups tested (wt, tg-6, tg-6-HD and tg-21). Mean CMR(glc) was higher in tg-6 (+72%), tg-6-HD mice (+43%) and tg-21 (+22%) than in wt mice. Local CMR(glc) was higher in all 40 brain regions in tg-6 but only in 15 and 8 regions in tg-6-HD and tg-21 mice. These results show that prolonged increases in hematocrit did not alter cerebral oxygen delivery at a decreased CBF and increased CMR(glc). Hemodilution suggests that high blood viscosity is a cause of the decrease in CBF and partly of the increase in CMR(glc). Cerebral glucose metabolic rate may also be increased by a direct effect of Epo in the brain (tg-21 mice).
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Faculty of Clinical Medicine Mannheim, Mannheim, Germany. bv3@ix.urz.uni-heidelberg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Frietsch
authors.forename: Martin H
authors.initials: MH
authors.lastname: Maurer
authors.forename: Johannes
authors.initials: J
authors.lastname: Vogel
authors.forename: Max
authors.initials: M
authors.lastname: Gassmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kuschinsky
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Waschke
mesh_terms: D000818:Animals; D001809:Blood Viscosity / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006400:Hematocrit; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011086:Polycythemia / Q000097:blood* / Q000378:metabolism
chemical_list: D004921:Erythropoietin; D005947:Glucose