Abstract TP228: Differential Effect Of Serum From Intracerebral Hemorrhage And Small Vessel Disease Patients On Nonischemic Cerebral Arteries

Abstract

Introduction: There is evidence that circulating factors disrupt vessel function in the contralateral hemisphere after stroke. However, how different stroke subtypes, that have more severe vascular disruption, affect nonischemic vessels is unknown. Here, we compared circulating factors from human patients with distinct stroke subtypes of cardioembolic (CE), small vessel disease (SVD), and intracerebral hemorrhage (ICH). We hypothesized that serum from ICH patients would cause greater vascular dysfunction of nonischemic arteries than CE, and that serum from SVD patients would have an intermediate effect. Methods: Serum was obtained 24 hours poststroke from patients with SVD (n=3), ICH (n=4), and CE (n=7) and pooled. All patients had a medical history of hypertension. Only SVD and CE patients received tPA. Pooled serum 20% v/v was perfused into the lumen of 3 rd order posterior cerebral arteries (PCA, CE & ICH n=5, SVD n=6) that were mounted on glass cannulas and pressurized in an arteriograph chamber. Blood brain barrier (BBB) permeability and vascular reactivity was studied to investigate effects on myogenic tone and endothelial function. Data are presented as mean±SEM. Results: All vessels reacted myogenically at pressures ≥40 mmHg. However, serum from ICH patients caused a significant increase in tone at 20 mmHg vs. CE and SVD groups: 37.5±1.6 vs. 9.0±1.9% and 13.0±4.8% p<0.05. There was no difference in dilation to NS309; however, constriction to nitric oxide synthase (NOS) inhibition with L-NAME was impaired with SVD and ICH serum compared to CE: 14.0±2.3% vs. 4.6±0.8% (p<0.05) and 5.8±2.1% (p=0.09). However, reactivity to sodium nitroprusside, an NO donor, was not different between groups. Serum caused an increase in BBB permeability over time that was not different with the different serums. Conclusions: Circulating factors from ICH, SVD and CE patients had differing vascular effects on nonischemic cerebral arteries. Serum from ICH patients was vasoconstrictive, potentially due to hemostatic factors, whereas serum from both SVD and ICH patients had impaired NO reactivity demonstrating endothelial dysfunction. These effects of ischemic stroke could affect the contralateral hemisphere and contribute to outcome and therapeutic responses.