434 Xylazine quantitation in Puerto Rican drug users and cardiotoxic protein markers profile expression analysis

Objectives/Goals: Our research addresses critical gaps by examining the prevalence, blood concentrations, and health implications of xylazine abuse, with a focus on its cardiotoxic effects. We aim to map the geographic distribution of xylazine use across Puerto Rico and characterize its impact on cardiomyocytes at relevant exposure levels. Methods/Study Population: To accurately detect and quantify xylazine in blood samples, we will employ chromatographic techniques coupled with mass spectrometry (UPLC/MS or GC/MS). The xylazine prevalence across the island will be mapped based on health system classifications. Samples will be categorized according to the eight healthcare regions of Puerto Rico, as defined by the “Administración de Seguros de Salud” (ASES), ensuring comprehensive geographic representation. We will investigate the expression profiles of proteins associated with cardiac injury and dysfunction in human cardiomyocytes and in the blood of drug users. Blood samples will be provided by “Iniciativa Comunitaria.” We will assess the xylazine effects on human cardiomyocyte viability and identify key biomarkers of cardiotoxicity induced by xylazine exposure. Results/Anticipated Results: In previous research, we demonstrated that xylazine induces cell death in endothelial cells through both extrinsic and intrinsic pathways. We also observed an increase in reactive oxygen species (ROS) levels after drug exposure, indicating oxidative stress as a potential mechanism of toxicity. Additionally, DNA damage was detected. Given the known relationship between endothelial damage and cardiomyocyte dysfunction in drug-induced cardiotoxicity, we hypothesize that xylazine concentrations vary regionally within Puerto Rico and that chronic xylazine abuse will elevate markers of cardiac injury and dysfunction at common user doses. Discussion/Significance of Impact: The increasing xylazine abuse, particularly in Puerto Rico, represents a critical public health challenge. Our study will fill a knowledge gap by providing crucial data on xylazine’s cardiotoxicity and mapping its geographic prevalence, with the potential to advise healthcare approaches and improve care for drug-using Hispanic populations.