Autonomic Control of the Heart

Cardiac Afferent Neurons

Cardiac control, first and foremost, depends on cardiovascular sensory transduction by populations of afferent neurons in nodose, dorsal root, intrinsic cardiac, stellate, and middle cervical ganglia. Normally, these afferent inputs evoke a balanced and integrated control of regional cardiac function that involves central and peripheral aspects of the ANS ( ). With respect to evolving cardiac pathology, however, nociceptive sensory inputs arising from the ischemic heart represent a stimulus that destabilizes neural network interactions throughout the hierarchy ( ), contributing to an increased potential for sudden cardiac death ( ). As a corollary, targeting these multilevel reflex pathways represents an emerging neuromodulation-based, therapeutic option for managing cardiac arrhythmia, angina, and/or pump failure.

The afferent sensory neurites can be mechanosensory, chemosensory or multimodal in nature ( ). The chemicals that are transduced include adenosine, adenosine triphosphate (ATP), bradykinin, substance P, and other peptides ( ). It is also known that the transduction properties of cardiac sensory neurites involve a number of ion species in situ ( ). There are also mechanosensory afferent neurites located in the fibrous coating of the major vessels adjacent to the heart (the aortic arch) and in the carotid sinus. These neurites respond to change in length and stretch of the vessel walls and transduce information to the nucleus tractus solitarius (NTS).

The characteristics of afferent activity depend on their spheres of influence as defined by their soma and sensory neurite location, the strength of the applied stimulus, the context/history of the applied stimulus, and the potential for information processing ( ). Furthermore, the time course of sensory transduction can outlive the primary stimulus; that is to say, sensory inputs can exhibit memory functions ( ). The net result of this organization is that limited numbers of afferent inputs are capable of responding to and transducing complex sensory environments in short-, mid-, and long-time frames.

While bipolar, cardiac afferent neurons in nodose ganglia project to neurons in the NTS of the medulla oblongata ( ), those in the dorsal root ganglia project first to spinal cord neurons ( ). Petrosal ganglia project to the NTS ( ). Autonomic sensory inputs, acting via central interneurons, reflexly modulate cardiac parasympathetic efferent preganglionic neurons in the medulla and spinal cord sympathetic efferent preganglionic neurons, respectively, for the control of cardiac adrenergic and cholinergic efferent outflow ( ).

Cardiac Efferent Neurons

Cardiac tissues are modulated by sympathetic and parasympathetic motor neurons as well as circulating hormones. Activation of the sympathetic nervous system (SNS) increases heart rate, blood pressure, and cardiac contractility ( ). In relation to electrophysiological properties, cardiac efferent sympathetic activation enhances cardiac electrical conduction by shortening the action potential (AP) duration, enhancing atrioventricular nodal conduction, and increasing sinoatrial firing rate ( ). Parasympathetic activity exerts directionally opposite effects, exerting negative chronotropic, inotropic, and dromotropic effects ( ). Sympathetic-parasympathetic interactions for control of regional cardiac function may be manifest at the end-effectors ( ), within peripheral autonomic ganglia ( ), and within the CNS ( ).

Cardiac, sympathetic efferent preganglionic neurons located in the caudal cervical and cranial thoracic spinal cord project axons via the right- and left-sided spinal nerves to sympathetic efferent postganglionic neurons in ganglia located in the neck and thorax ( ). The latter neurons are located in the superior and middle cervical ganglia, stellate ganglia, and mediastinal ganglia ( ) with lesser numbers synapsing with sympathetic efferent postganglionic neurons located throughout the major atrial and ventricular ganglionated plexuses ( ). The right postganglionic sympathetic nerve fibers predominantly cover the ventral aspect, whereas the left predominantly cover the dorsal aspect of the heart ( ). Neural network interconnections between the CNS and extracardiac ganglia, including those intrinsic to the heart, facilitate coordination of regional cardiac electrical and mechanical function to ensure adequate cardiac output to meet whole body flow requirements ( ).

The parasympathetic efferent projections to the heart reduce heart rate and cardiac contractility, delay atrioventricular electrical conduction, and prolong ventricular AP duration ( ). The preganglionic soma are located within the nucleus ambiguous and the dorsal motor nucleus of the medulla ( ) with peripheral projections coursing the 10th cranial nerve (vagus). The preganglionic fibers project to divergent aggregate of intrinsic cardiac ganglia, located in atrial and ventricular tissues ( ). Specific ganglia preferentially control different aspects of cardiac function such as sinoatrial node activity, but there is sufficient redundancy within the system that even when one ganglia is removed, other ganglia within the intrinsic cardiac nervous system (ICNS) take over the control of that region ( ). As the result of convergence of parasympathetic, preganglionic projection neurons to the ICNS and interconnections manifest between aggregates of intrinsic cardiac ganglia, there is balance in control of all regions of the heart, as exerted from right and left vagus ( ).

Local Circuit Neurons

Local circuit neurons exist throughout all of the intrathoracic ganglia, including the ICNS ( ). By local circuit neurons we mean neurons that are not directly transducing cardiac indices (cardiac afferent neurons) or having direct motor function. These neurons play a principal role in integrating sensory inputs from the heart and major intrathoracic vessels with descending inputs from central autonomic motor neurons ( ). The local circuit neurons can be responsible for processing only afferent or efferent information or they can be convergent; in other words, they receive both afferent and efferent inputs ( ). There is another population of local circuit neurons that don’t receive either afferent or efferent inputs and their function remains elusive and yet to be determined.