Hemodynamic effects of recombinant human erythropoietin on the central nervous system after subarachnoid hemorrhage: reduction of microcirculatory impairment and functional deficits in a rabbit model.
OBJECTIVE
The authors investigated the hemodynamic effects of recombinant human erythropoietin (rhEPO) after subarachnoid hemorrhage (SAH) in rabbits.


METHODS
The authors used male New Zealand White rabbits in this study divided into the following groups: SAH plus saline (16 rabbits), SAH plus low-dose rhEPO (16 rabbits; 1500 IU/kg on Day 0 and 500 IU/kg on Days 2 and 4), SAH plus high-dose rhEPO (10 rabbits; 1500 IU/kg on Days 0, 2, 4, and 6), and sham (6 rabbits). Computed tomography perfusion studies and CT angiography were performed for 1 hour after SAH on Day 0, and once each on Days 2, 4, 7, 9, and 16 after SAH. Assessments of neurological function and tissue histology were also performed.


RESULTS
The mortality rate was significantly lower after rhEPO treatment (12%) than after saline treatment (44%) (p < 0.05). Neurological outcomes in the low-dose and high-dose rhEPO groups were better than in the saline group after SAH (p < 0.05), and the cerebral blood flow in the high-dose rhEPO group was greater than that in the saline group (p < 0.05). The mean transit time was significantly lower on Days 2 and 4 in the low-dose and high-dose rhEPO groups than in the saline group, but increased significantly on Day 7 in both groups (p < 0.05). The hematocrit increased significantly from baseline values in the high-dose and low-dose rhEPO groups on Days 4 and 7, respectively (p < 0.05).


CONCLUSIONS
Treatment with rhEPO after experimental SAH is associated with improved cerebral blood flow and microcirculatory flow as reflected by lower mean transit times. Improved tissue perfusion correlated with reduced mortality and improved neurological outcomes. Further investigation of the impact of increasing hematocrit on hemodynamic changes is needed.
Murphy
Amanda M
AM
Imaging Program, Lawson Health Research Institute, London, Ontario, Canada.
Xenocostas
Anargyros
A
Pakkiri
Pria
P
Lee
Ting-Yim
TY
D000792:Angiography; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D002531:Cerebellum / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology*; D006400:Hematocrit; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D023421:Models, Animal; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*
D011994:Recombinant Proteins; D004921:Erythropoietin