Erythropoietin prevents delayed hemodynamic dysfunction after subarachnoid hemorrhage in a randomized controlled experimental setting

Abstract

Introduction: Erythropoietin (EPO) was proven as a promising approach for experimental subarachnoid hemorrhage (SAH). Clinical data are, however, inconclusive so far. A detailed characterization of specific EPO effects could facilitate the design of trials. The aim of the present investigation was, therefore, to characterize these effects on prevention of delayed proximal cerebral vasospasm (CVS), impaired microcirculation and cerebral blood flow (CBF) after experimental SAH.

Methods: 27 male Sprague-Dawley rats were randomized in 3 groups: Sham, SAH control, and SAH EPO. SAH was induced by injection of 0.2ml autologous blood into the cisterna magna on days 1 and 2. Animals of the SAH EPO group received 5000iU rh EPO α 6h after the 2nd SAH intravenously. Surviving animals were examined on day 5 by MR perfusion weighted imaging (PWI). Cerebral blood flow (CBF) and volume (CBV) were determined by PWI, proximal CVS by basilar artery (BA) diameter, and neuroprotection by hippocampal cell count (CA1-CA4).

Results: BA diameter was significantly reduced in both SAH groups, but improved significantly after EPO (Sham: 144±3μm, SAH control: 79±6μm, SAH EPO 109±4μm). The rrCBV ratio was 8.78±0.72 Sham, 5.14±1.73 SAH control, and 6.80±0.44 SAH EPO. The improvement by EPO did not reach statistical significance. RrCBF ratio was also significantly reduced in both SAH groups, but was significantly improved by EPO (Sham: 8.78±0.34, SAH control: 4.26±1.05, SAH EPO 5.85±0.46). Surviving neuronal cells were significantly reduced in SAH controls in all areas, but in SAH EPO only in CA1.

Conclusion: The present data suggest that an EPO application in a timely distance to the SAH is sufficient to prevent delayed proximal CVS, but that the doses were insufficient to improve microcirculation or to be directly neuroprotective.

Keywords: Animal model; Delayed ischemic neurological deficit; Erythropoietin; Rat double-hemorrhage model; Subarachnoid hemorrhage; Vasospasm.