Abstract
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.
Highlights
Recent research supports that over-activation of the carotid body plays a key role in metabolic diseases like type 2 diabetes
Our results demonstrate that pharmacological and electrical activation of a chemo-afferent response is reproducible in a human-sized carotid sinus nerve (CSN), and more importantly, that blocking such activation through kilohertz frequency alternating current (KHFAC) modulation is feasible in anesthetised pigs
Results from the current study demonstrate that pharmacological and electrical activation of a chemo-afferent CSN response is reproducible in anesthetised pigs
Summary
Recent research supports that over-activation of the carotid body plays a key role in metabolic diseases like type 2 diabetes. 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. Nerve conduction may be temporarily blocked by applying kilohertz frequency alternating current (KHFAC) electrical stimulation, as action potentials are arrested when they reach the depolarising charge field of the electrode[4] This mode of CSN conduction-block restored insulin sensitivity and glucose tolerance in a rat model of type 2 diabetes[3]. These observations may have important clinical implications and should warrant further model refinement of electrodes and paradigms prior to clinical use
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