Splenic artery denervation: target micro-anatomy, feasibility, and early preclinical experience
Section snippets
INTRODUCTION
The spleen plays an important role in the immune response to inflammatory conditions including cancer, myocardial infarction, and atherosclerosis (Fig 1).1 The autonomic nervous system responds to inflammatory stimuli, in part, by upregulating sympathetic nerve trafficking to the spleen, which can mobilize monocytes to sites of tissue injury and release cytokines that modulate the inflammatory response.2, 3 Device-based neuromodulation of the spleen's neural pathways is an emerging therapeutic
Animal models and experimental overview
All animal experiments were performed at CBSET, Inc. (Lexington, Massachusetts) and adhered to the Guide for the Care and Use of Laboratory Animals20 an institutional animal care and use committee approved protocol. In total, 27 castrated male Yorkshire swine (68.0 ± 24.8 kg) were studied. A detail outline of the experimental groups and study design can be found in the Supplement (Table S1).
Group 1 consisted of N = 5 control pigs evaluated for splenic artery anatomy and histology and baseline
Splenic artery anatomy and histology
Splenic artery anatomy was grossly and microscopically evaluated in untreated healthy swine to elucidate the relationship of the spleen and splenic artery to surrounding organs and structures including the pancreas and lymph nodes (Fig 2, A). For the purposes of mapping interventional targets for SDN, the proximal splenic artery was defined as the segment coursing along the pancreas, and the distal splenic artery was defined as the segment coursing along the splenic hilus. The mid splenic
DISCUSSION
The nervous system is an important regulator of inflammation,3, 25 and the spleen is an important reservoir of monocytes2 that can be mobilized in response to sympathetic nervous system9 and cytokine26, 27 signaling pathways. Device-based neuromodulation is a promising therapeutic approach for managing disease-states characterized by dysregulated immune responses. Percutaneous endovascular SDN is a highly novel approach to disrupting the mobilization of inflammatory cells from the spleen
ACKNOWLEDGMENTS
Conflicts of Interest: The authors have no conflicts of interest to declare. All authors have read the journal's policy on disclosure of potential conflicts of interest and authorship agreement.
This work was supported by unrestricted research sponsorship from Lavita. The manuscript was prepared independently by CBSET Inc, a private nonprofit research organization, which also provided partial support for this work.
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Mazen Albaghdadi, MD is an Instructor in the Department of Medicine in the Division of Cardiology at Massachusetts General Hospital, Harvard Medical School. Dr. Albaghdadi is interventional cardiologist and physician-scientist with a research interest in translating novel diagnostic and therapeutic medical devices to improve patient care.