Details

Autor(en) / Beteiligte

• Penn, Angela, M.D
• Mohr, Alicia M., M.D
• Shah, Salil G., M.D
• Sifri, Ziad C., M.D
• Kaiser, Vicki L., Ph.D
• Rameshwar, Pranela, Ph.D
• Livingston, David H., M.D

Titel

Dose-Response Relationship between Norepinephrine and Erythropoiesis: Evidence for a Critical Threshold

Ist Teil von

• The Journal of surgical research, 2010-10, Vol.163 (2), p.e85-e90

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2010

Link zum Volltext

Quelle

ScienceDirect Journals (5 years ago - present)

Beschreibungen/Notizen

• Background Severe traumatic injury elicits a neuroendocrine response that activates the sympathetic nervous system. Our previous work suggests that norepinephrine (NE) influences the bone marrow (BM) erythropoietic response. However, the dose-response relationship between NE and erythropoiesis remains unclear. Materials and Methods Two days following chemical sympathectomy with 6-hydroxydopamine (6-OHDA) or injection with saline vehicle (SHAM), male Sprague-Dawley rats were infused continuously with either saline (NS) or increasing doses of NE for 5 d via osmotic pumps. Erythropoiesis was assessed by growth of erythroid progenitor colonies (BFU-E and CFU-E for early and late progenitors, respectively). Results Following chemical sympathectomy with 6-OHDA, both BFU-E and CFU-E growth is inhibited (42%∗ and 43%∗ versu s 100% SHAM, ∗ P < 0.05). SHAM rats with continuous infusion of exogenous NE show a clear dose-response inhibition of both BFU-E and CFU-E colony growth. In the 6-OHDA rats, continuous infusion of NE restored BFU-E and CFU-E growth at 10−8 g/h and 10−9 g/h, respectively. Conclusions Erythroid precursor colony growth is inhibited in sympathectomized rats. In addition, supraphysiologic doses of exogenous NE inhibit normal erythropoiesis in a dose-dependent fashion. Following chemical sympathectomy with 6-OHDA, exogenous NE restores erythropoiesis in a narrow window. Therefore, NE has a complex interaction within the BM and the elevation of NE following traumatic injury impacts BM erythropoietic function.