Neurocardiology: translational advancements and potential

Abstract

In our original white paper published in the The Journal of Physiology in 2016, we set out our knowledge of the structural and functional organization of cardiac autonomic control, how it remodels during disease, and approaches to exploit such knowledge for autonomic regulation therapy. The aim of this update is to build on this original blueprint, highlighting the significant progress which has been made in the field since and major challenges and opportunities that exist with regard to translation. Imbalances in autonomic responses, while beneficial in the short term, ultimately contribute to the evolution of cardiac pathology. As our understanding emerges of where and how to target in terms of actuators (including the heart and intracardiac nervous system (ICNS), stellate ganglia, dorsal root ganglia (DRG), vagus nerve, brainstem, and even higher centres), there is also a need to develop sensor technology to respond to appropriate biomarkers (electrophysiological, mechanical, and molecular) such that closed-loop autonomic regulation therapies can evolve. The goal is to work with endogenous control systems, rather than in opposition to them, to improve outcomes.

Keywords: autonomic nervous system; cardiac function; parasympathetic; sympathetic nervous system.

Figure 1. Network interactions occurring within and between peripheral ganglia and the central nervous system for autonomic control of the heart

The cardiac nervous system is composed of multiple (distributed) processing centres from which independent and interdependent neural feedback and feed‐forward neural circuits interact to control regional cardiac electrical and mechanical function. Afferent projections are indicated in blue and efferent projections in red (dashed lines, preganglionic; continuous lines, postganglionic). The intrinsic cardiac nervous system (ICNS) possesses sympathetic (Sympath) and parasympathetic (Parasym) efferent postganglionic neurons, local circuit neurons (LCN) and afferent neurons. Extracardiac intrathoracic ganglia contain afferent neurons, LCN and sympathetic efferent postganglionic neurons. Neurons in intrinsic cardiac and extracardiac networks form nested feedback loops that act in concert with CNS feedback loops (spinal cord, brainstem, hypothalamus and forebrain) to coordinate cardiac function on a beat‐to‐beat basis. These systems demonstrate plasticity which underlies adaptations to acute and chronic stressors. Ang I, angiotensin I; Ang II, angiotensin II; AC, adenylate cyclase.

Figure 2. Key structures of the central autonomic network

The anatomical location of key structures in the central autonomic network.

Figure 3. Neurocardiology is based on the premise that cardiac control must be evaluated in the context of the end‐organ substrate and interdependent interactions within multiple levels of the cardiac nervous system

Imbalances in autonomic responses, while beneficial in the short term, ultimately contribute to the evolution of cardiac pathology. As our understanding of where to target emerges in terms of actuators (including the heart and intracardiac nervous system (ICNS), stellate ganglia, dorsal root ganglia (DRG), brainstem and even higher centres), there is also a need to develop sensor technology to respond to appropriate biomarkers (electrophysiological, mechanical and molecular) such that closed‐loop autonomic regulation therapies can evolve. The goal is to work with endogenous control systems, rather than in opposition to them, to improve outcomes.