Abstract 2283: Relative Deficiency of Vascular Endothelial Growth Factor (VEGF) in Subarachnoid Hemorrhage.
Cerebral vasospasm (VS) after subarachnoid hemorrhage (SAH) is associated with delayed cerebral ischemia and poor neurological outcome. We have recently reported that shortly after SAH, there is a dramatic elevation in the levels of the endogenous VEGF-antagonist soluble fms-like tyrosine kinase-1 (sFlt1), particularly among individuals that will later develop symptomatic VS (sVS). Based on this observation we have proposed that an imbalance in the levels of endogenous angiogenic and anti-angiogenic factors occurs in SAH. In this study we examined the association of cerebrospinal fluid (CSF) levels of VEGF, sFlt1, and VEGF/sFlt1 ratio with vasospasm in SAH patients. We studied seventeen patients with Fisher Grade 3 aneurysmal SAH and five controls with no prior history of neurological disorders who underwent lumbar puncture for headache and had normal CSF studies. Demographics and medical history were documented. Patients were followed prospectively and samples of CSF were obtained within 48-hours of symptoms onset. VEGF and sFlt1 levels were determined using commercially available ELISA tests (R&D Systems). SAH subjects were subcategorized into those with sVS and those who did not develop symptomatic VS (noVS). sVS was defined as the occurrence of neurological deterioration in the setting of angiographically proven VS and in the absence of other conditions that could explain the neurological decline. Ratios and levels of the compounds of interest in the different groups were compared using the nonparametric Mann-Whitney U test. Age, history of hypertension, exposure to elicit drugs, RBC count in the CSF and proteinorrachia were not statistically different between sVS and noVS groups. Similar to what has been described by others, compared to controls, SAH patients showed a trend towards having higher VEGF levels in the CSF (106±53 vs. 180±172 pg/mL); this, however, did not reach statistical significance (p>0.05). The CSF levels of sFlt1 were 46±23 pg/mL in the control group and 598±423 pg/mL in the SAH group (p=0.01). Among patients with SAH, sFlt1 levels were 1018±797 pg/mL in the sVS group and 304±184 pg/mL in the noVS group (p=0.01). The mean VEGF/sFlt1 ratios were 2.27±0.25 in controls, 0.39±0.25 in SAH patients, 0.23±0.10 in the sVs group, and 0.61±26 in the noVS group (p=0.02). An early elevation in sFlt1 levels and a relative deficiency of VEGF occur in the CSF of SAH patients, particularly in those with sVS. These results suggest that an imbalance in the production of angiogenic and anti-angiogenic factors may be part of the pathogenesis of VS and that analysis of these molecules might potentially have a role in predicting sVS in SAH patients.
- © 2012 by American Heart Association, Inc.