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J. ANDREW ARMOUR, MD, PhD*
Center of Research Hôpital du Sacré-Coeur Université de Montréal Montréal, Québec, Canada

The little brain on the heart

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he function of the cardiovascular neuronal hierarchy is ultimately to match cardiac output to regional body blood flow demands. To comprehend how the varied elements of this hierarchy interact to accomplish this task, we must determine howits peripheral (intrathoracic and cervical ganglion) and central neurons communicate on an ongoing basis in the coordination of regional cardiac indices.1 The cardiac neuronal hierarchy can be represented as a massively parallel and, for the most part, stochastic control system such that stable cardiac control generally occurs in the absence of obvious cause and effect (see sidebar below). Itsperipheral neuronal interactions display emergent properties, functioning as they normally do in a highly optimized fashion to tolerate normal cardiac perturbations. From a clinical perspective, excessive activation of

select elements within the cardiac neuronal hierarchy has been thought to result in the genesis of atrial2 or ventricular3 arrhythmias. Indeed, the functional interconnectivity ofthe various neurons in the hierarchy is so organized that the whole can be catastrophically disabled by cascading failures initiated by relatively minor abnormal inputs. Defining the function of each of its populations may be required to understand how, for instance, excessive activation of select elements initiates cardiac arrhythmias. Such an understanding is required if one is to manage thisstate from a neurocardiological perspective. This brief review presents the anatomy and function of this hierarchy’s afferent and efferent neurons and discusses the putative interactions that occur among its neuronal populations. ■ ANATOMY

The cardiac neuronal hierarchy
The cardiac neuronal hierarchy can be represented as a massively parallel and, for the most part, stochastic control system suchthat stable cardiac control occurs in the absence of obvious cause and effect (ie, it displays emergent properties). This hierarchy displays robust external behavior while matching cardiac output to whole-body blood flow demands. Its target organ component, the “little brain on the heart,” transduces centripetal and centrifugal inputs in the coordination of regional cardiac electrical andmechanical indices. Although optimized to tolerate normal perturbations, the system can be catastrophically disabled by cascading failures initiated by relatively minor input changes. What it cannot tolerate, as these are not design features, are: • Rearrangement of its interconnecting parts • Excessive activation of select components that engender cardiac pathology (cf, arrhythmias). Therapeutictargeting of select components of the hierarchy should take into consideration the emergent properties of the whole.

Cardiac afferent neurons Pain associated with myocardial ischemia is frequently referred to a patient’s left upper limb and/or anterior thoracic wall.4 As a result, the somata of cardiac afferent neurons are assumed to be located primarily in left-sided, cranial thoracic dorsal rootganglia. Anatomic evidence indicates that cardiac afferent neurons are distributed relatively evenly throughout the nodose ganglia and the C7 to T4 dorsal root ganglia bilaterally.5 They are also located in intrathoracic ganglia, including those intrinsic to the heart.1,6 Cardiac efferent neurons Cholinergic neurons. The somata of parasympathetic efferent preganglionic neurons that synapse withcholinergic efferent postganglionic neurons on the heart are located primarily in the ventral lateral region of the nucleus ambiguous of the medulla;7 fewer are found in its dorsal motor nucleus and the zone intermediate between these two medullary nuclei.8 Cardiac preganglionic motor neurons in individual medullary loci project axons to parasympathetic efferent postganglionic neurons distributed...