Direct carotid sinus nerve stimulation in anesthetized human subjects

Fig. 1. Schematic representation of C-FINE applied to the CSN. (Left) The C-FINE causes a flat geometric re-configuration of enclosed tissue improving access to select nerve fibers. In the boxed region, note the application of the C-FINE close to the distal terminal of the CSN. Abbreviations: CCA = Common Carotid Artery, ECA = External Carotid Artery, ICA = Internal Carotid Artery.

Fig. 2. Stimulation protocol. Contact selection (A) was followed in all patients. The recruitment protocol (B) was followed in all patients for at least one C-FINE contact. The repetition protocol (C) was followed in some patients when there was adequate operative time. Abbreviations: PA = Pulse Amplitude, PW = Pulse Width.

Fig. 3. Patient 008 blood pressure and heart rate tracing during CSN Stimulation. A small delay can be seen between the application of stimulus and response. Note that different contacts were stimulated in different stimulation epochs which explains the heterogeneity of wave morphology. The stimulation epoch marked by the arrow caused BP to drop enough to trigger a protocol-mandated immediate withdrawal of stimulation.

Fig. 4. Maximum blood pressure drops and recoveries per patient. All drops are relative to the baseline value 30 s before stimulation (not the patient resting BP). Recovery is relative to the value achieved during stimulation, occurring within 30 s after stimulation ceased. Note that responses were larger in patients with pre-stimulation baseline SBP > 120mmHg.

Fig. 5. Patient 009 blood pressure and heart rate tracing during CSN stimulation. Note the progressive and cumulative drop in SBP across the entire stimulation period—an effect seen in most responders. Note also the different channels used to in each cluster of stimulation. The arrow to the right of the 35-minute marker indicates the administration of phenylephrine (a vasoconstrictor given to support BP) by the anesthesiologist.

Fig. 6. Secondary Analysis of Effects of CSN stimulation on SBP, DBP, and HR with 30 s washout. CSN stimulation caused the largest drops in SBP (A) with associated (smaller) drops in diastolic blood pressure (B). HR changes caused by CSN stimulation (C) tracked with SBP & DBP changes. The pooled analysis (D) suggested CSN stimulation, on average, dropped SBP by 11.2 mmHg, DBP by 6.3 mmHg, and HR by 5.8 bpm in this study.

Fig. 7. Secondary Analysis of Recovery on SBP, DBP, and HR after CSN stimulation withdrawal using 30 s washouts. Posterior means and confidence intervals per patient were calculated to compare post-stimulation with pre-stimulation levels for SBP, DBP, and HR (A, B,C). Pooled posterior means and confidence intervals including all patients are also presented (D). Cessation of CSN stimulation led to recovery in all metrics.