Keywords

Cardiac sympathetic innervation: Sympathetic remodeling: Heart failure: Catecholaminergic: Digital twin: 3D Scaffolding

Abstract

Cardiac sympathetic innervation plays a vital role in regulating various heart functions, and its remodeling has been linked to a range of cardiovascular diseases. To understand cardiac sympathetic innervation and remodeling, it is important to elucidate the topographical distribution and morphology of sympathetic axons in the whole left ventricle. However, immunohistochemistry (IHC) on whole heart tissues presents challenges due to their thickness, as conventional methods label only small sections. This disrupts tissue integrity and neural connections. To overcome this, we developed a whole flat-mount technique to process the rat heart (ventricle thickness: 3 mm). We performed cardiac sympathetic nerve imaging in the rat left ventricle, specifically investigating changes post myocardial infarction in 8 rats. We analyzed the differences in distribution and density of cardiac sympathetic nerve terminals between the infarcted and control tissues, specifically noting the remodeling of sympathetic axon innervation patterns and distinct structures. In normal control rats, the TH-IR axon network covered the whole ventricle, extending from the base to the apex. In heart failure rats, the TH-IR axon network failed to cover the infarct zone, creating a large “dark area,” distal to the ligation of the anterior descending coronary artery (LAD) and extending toward the apex, while dense hyperinnervation was observed along the infarct border regions. To establish a 3D anatomical map of innervation, the distribution of TH-IR axons was traced, digitized, and integrated into a heart scaffold using Neurolucida 360 and the organ mapping tool. These models revealed distinct remodeling patterns, highlighting structural changes of sympathetic axons in heart failure in 3D. This 3D model serves as the anatomical basis for functional mapping and studying sympathetic remodeling in pathological conditions such as heart failure.

Thesis Completion Year

2026

Thesis Completion Semester

Spring

Thesis Chair

Cheng, Zixi

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Neuroscience

Language

English

Access Status

Open Access

Length of Campus Access

None

Campus Location

Orlando (Main) Campus

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Rights Statement

In Copyright