1088 Elevated Intracranial pCO2 Protects Against Ischemic Stroke and Disability through Amelioration of Endothelial Dysfunction and Early Expression of Angiogenic Factors

INTRODUCTION: Despite thrombectomy efficacy, rates of moderate to severe disability remain high. The Perfusion Reconnaissance of the Ischemic Stroke Microenvironment (PRISM) study was designed to analyze perfusion imaging and sampling of systemic and intracranial blood, to better understand dynamic blood gas changes and early proteomic response. METHODS: Patients enrolled in the PRISM study with point-of-care arterial blood gas (ABG) and proteomic analysis (Olink, Boston, MA) were included for analysis. ABG and proteomic analysis were assessed intracranially and systemically. Intracranial arterial samples were collected during thrombectomy through the microcatheter prior to stentriever deployment. ABG was analyzed using the iSTAT-1 point-of-care machine (Abbott Laboratories, Chicago, IL). Olink proteomics was used to assess expression of 184 proteins using a proximity extension assay. Outcome measures (NIHSS scores, mRS) were assessed. Statistical analysis included linear regression and Pearson correlation with a p value of <0.05. RESULTS: The study involved dual arterial blood samples from 11 patients, with an NIHSS admit score of 18.1 ± 9.8 and discharge score of 9.7 ± 8.4. Elevated intracranial pCO2 correlated with lower NIHSS scores at discharge (R2=0.5876, p=0.016), which was not observed systemically. On proteomic assessment, high pCO2 levels were associated with increased expression of ANG/angiogenin (R2=0.7054, p=0.01530), a known angiogenic factor. Elevated ANG expression was also associated with improved NIHSS scores at discharge (R2=-0.6192, p=0.0422). Further, increased ANG expression was strongly correlated with intravascular proteins known to promote blood vessel stability, prevent endothelial dysfunction, and induce angiogenesis and collateral support (APOM, TIE-1, TNFB, TGFBI). CONCLUSIONS: Elevated intracranial pCO2 correlates with elevated ANG expression, promoting a cascade of pro-angiogenic and endothelium-protective intravascular proteins, leading to improved stroke outcomes.