Abstract Body: Introduction
Neuromodulation of the baroafferent pathway via direct carotid sinus nerve (CSN) stimulation is recognized as a potential therapeutic modality for treating uncontrolled hypertension. Although proof of concept has been demonstrated acutely in humans, there are many questions that remain in both acute and chronic applications. A translational non-companion large animal model is vital for safe development of this modality. Here we present data on the effects of CSN and baroafferent stimulation in farm pigs.
Hypothesis
We hypothesized that an effective CSN-bioelectode interface in the pig would demonstrate significant and reproducible reductions in blood pressure in tandem with pulse rate (PR).
Methods
Acute CSN stimulation was investigated in 9 anesthetized Yorkshire pigs. Following general anesthesia, CSNs were exposed and an application-specific electrode was placed. A fixed current paradigm was employed at constant 100Hz and 100µs pulse width. Following contact mapping to identify the baroafferent neurointerface, electrical current was escalated to establish dose-response curves. The primary outcome was systolic blood pressure (SBP) and secondary outcomes were diastolic pressure (DBP) and PR. Data were analyzed in Matlab to extract the baseline BP and PR, during and following stimulation. Statistical calculations used a one-sample Wilcoxon signed rank test. Explanted electrodes with surrounding tissue were evaluated using micro-computed tomography (μCT) and histologically.
Results
Six of 9 animals were responders (n=7, 2 sides were stimulated in one animal), CSN stimulation caused average (mean±SD, p<0.001) decreases in SBP (6.8±7.2mmHg) and DBP (3.9±3.7mmHg), which tracked closely with decreases in PR (6.2±5.7bpm). Average maximum decreases were: SBP, 9.3±9.9mmHg; DBP, 7.7±6.4mmHg; and PR, 9.7±8.3bpm. Upon stimulation withdrawal, there was near-immediate recovery of both BP and HR. μCT and histological analysis of tissue samples demonstrated inter-animal anatomic heterogeneity.
Conclusions
CSN stimulation causes reproducible reduction in BP synchronous with PR drops followed by near immediate recovery of both with stimulation withdrawal. Variations in animal response may be due to anatomical variation in CSN anatomy that can be overcome with further anatomical study. Pigs provide a robust large-animal model for investigating CSN stimulation, offering a platform to better understand baroafferent stimulation as treatment for uncontrolled hypertension.