Hypotensive Effect of Electric Stimulation of Caudal Ventrolateral Medulla in Freely Moving Rats.

Background and Objectives: An altered sympathetic function is established in primary arterial hypertension (PAH) development. Therefore, PAH could be targeted by applying an electric current to the medulla where reflex centers for blood pressure control reside. This study aims to evaluate the electric caudal ventrolateral medulla (CVLM) stimulation effect on blood pressure and animal survivability in a freely moving rat model. Materials and Methods: A total of 20 Wistar rats aged 12-16 weeks were randomly assigned to either: the experimental group (n = 10; electrode tip implanted in CVLM region) or the control group (n = 10; tip implanted 4 mm above the CVLM in the cerebellum). After a period of recovery (4 days), an experimental phase ensued, divided into an "OFF stimulation" period (5-7 days post-surgery) and an "ON stimulation" period (8-14 days post-surgery). Results: Three animals (15%, one in the control, two in the experimental group) dropped out due to postoperative complications. Arterial pressure in the experimental group rats during the "OFF stimulation" period decreased by 8.23 mm Hg (p = 0.001) and heart rate by 26.93 beats/min (p = 0.008). Conclusions: From a physiological perspective, CVLM could be an effective deep brain stimulation (DBS) target for drug-resistant hypertension: able to influence the baroreflex arc directly, having no known direct integrative or neuroendocrine function. Targeting the baroreflex regulatory center, but not its sensory or effector parts, could lead to a more predictable effect and stability of the control system. Although targeting neural centers in the medullary region is considered dangerous and prone to complications, it could open a new vista for deep brain stimulation therapy. A possible change in electrode design would be required to apply CVLM DBS in clinical trials in the future.

Remotely Programmable Deep Brain Stimulator Combined with an Invasive Blood Pressure Monitoring System for a Non-Tethered Rat Model in Hypertension Research.

The control circuits of blood pressure have a strong neural regulatory element important in the pathogenesis of essential drug-resistant hypertension. Targeting lower medullary neural control mechanisms of blood pressure by electrical stimulation could be beneficial, and therefore, a novel device is needed. This paper presents a remotely programmable deep brain stimulator with an invasive continuous blood pressure monitoring system in a non-tethered rat model. The device is designed for lower medullary deep brain stimulation research with minimal interference to a daily animal routine. Electrodes were implanted in the caudal ventrolateral medulla. Animal survivability, catheter patency rates, and device data drift were evaluated. Eight out of ten rats survived the surgery and testing period with no or mild temporary neurological compromise. The study revealed that carotid catheters filled with heparinized glycerol ensure better catheter patency rates and blood pressure transduction. There was no significant drift in the device's pressure sensitivity during the experiment. To our knowledge, this is the first experimental study to show considerable animal survival after lower medullary implantation. Combining the ability to measure and monitor invasive blood pressure with a closed-loop brain pulse generator in a single device could be of potential value in future hemodynamic animal research.