Feasibility of kilohertz frequency alternating current neuromodulation of carotid sinus nerve activity in the pig.
Cathrine T FjordbakkJason A MirandaDavid SokalMatteo DonegàJaime ViscasillasThaleia-Rengina StathopoulouDaniel J ChewJustin D PerkinsPublished in: Scientific reports (2019)
Recent research supports that over-activation of the carotid body plays a key role in metabolic diseases like type 2 diabetes. Supressing carotid body signalling through carotid sinus nerve (CSN) modulation may offer a therapeutic approach for treating such diseases. Here we anatomically and histologically characterised the CSN in the farm pig as a recommended path to translational medicine. We developed an acute in vivo porcine model to assess the application of kilohertz frequency alternating current (KHFAC) to the CSN of evoked chemo-afferent CSN responses. Our results demonstrate the feasibility of this approach in an acute setting, as KHFAC modulation was able to successfully, yet variably, block evoked chemo-afferent responses. The observed variability in blocking response is believed to reflect the complex and diverse anatomy of the porcine CSN, which closely resembles human anatomy, as well as the need for optimisation of electrodes and parameters for a human-sized nerve. Overall, these results demonstrate the feasibility of neuromodulation of the CSN in an anesthetised large animal model, and represent the first steps in driving KHFAC modulation towards clinical translation. Chronic recovery disease models will be required to assess safety and efficacy of this potential therapeutic modality for application in diabetes treatment.
Keyphrases
- type diabetes
- endothelial cells
- liver failure
- photodynamic therapy
- drug induced
- cardiovascular disease
- induced pluripotent stem cells
- respiratory failure
- combination therapy
- peripheral nerve
- glycemic control
- aortic dissection
- cancer therapy
- squamous cell carcinoma
- adipose tissue
- weight loss
- extracorporeal membrane oxygenation
- metabolic syndrome