A CLOSED-LOOP ANTIHYPERTENSIVE DRUG-DELIVERY SYSTEM FOR MANAGEMENT OF HYPERTENSION AND BLOOD PRESSURE VARIABILITY

Objective: Hypertension remains the leading cause of cardiovascular (CV) morbidity and mortality worldwide. Despite current treatments, blood pressure (BP) control is often suboptimal, with BP variability (BPV) emerging as a significant risk factor for CV events. Novel wearable BP measurement technologies highlight the potential for improved BPV monitoring, underscoring the urgent need for targeted therapies. This study aims to develop an implantable, closed-loop system using esmolol hydrochloride to optimise BP control and minimise BPV.Design and method: A two-phase experimental approach is being undertaken using stroke-prone spontaneously hypertensive rats. Phase 1: Incremental doses of esmolol are administered via a subcutaneous pump following a fixed oral dose of amlodipine to establish dose-response curves. Phase 2: Proportional-integral-derivative (PID) algorithms derived from Phase 1 data will guide the timing and dosage of esmolol release. The closed-loop system will incorporate real-time BP and heart rate (HR) data to minimise BPV, measured by the coefficient of variation (CoV). Results: Preliminary findings indicate that locomotor activity significantly confounds BP and HR measurements. This underscores the importance of integrating activity data, obtained via radiotelemetry, into the development of the PID algorithms. The closed-loop system comprises: i) radiotelemetry-based BP, HR and activity measurement; ii) a controller with PID algorithms to determine esmolol dosing; iii) an implantable subcutaneous pump for drug delivery. A custom application enables live monitoring of BP, HR, and CoV during administration. Algorithm validation will be conducted on an existing BP dataset, with further refinement informed by real-time experimental data. Conclusions: The dose-response study highlights the influence of locomotor activity on BP, BPV and HR, necessitating its incorporation into algorithm design. Future steps include a dose-response experiment in anaesthetised swine to eliminate activity-related confounding prior to testing the closed-loop system in animal models. This novel approach holds promise for advancing BPV management through precise, real-time control.