Background: Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These treatments require detailed knowledge of the spatial location and distribution of cardiac autonomic nerves, however, there are controversies on this subject in humans. Objective: To provide a systematic overview of current knowledge on human anatomy of the cardiac autonomic nervous system. Results: In contrast to the often claimed assumption that human preganglionic sympathetic cardiac neurons originate mainly from thoracic spinal segments T1-T4 or T5, there is ample evidence indicating involvement of cervical spinal segment C8 and thoracic spinal segments below T5. Whether cervical ganglia besides the stellate ganglion play a role in transmission of cardiac sympathetic signals is unclear. Similarly, there is debate on the origin of cardiac nerves from different thoracic ganglia. Most human studies report thoracic cardiac nerves emerging from the first to fourth thoracic paravertebral ganglia; others report contributions from the fifth, sixth and even the seventh thoracic ganglia. There is no agreement on the precise composition of nerve plexuses at the cardiac level. After years of debate, it is generally accepted that the vagal nerve contributes to ventricular innervation. Vagal distribution appears higher in atria, whereas adrenergic fibers exceed the number of vagal fibers in the ventricles. Conclusion: Anatomy of the human cardiac autonomic nervous system is highly variable and likely extends beyond generally assumed boundaries. This information is relevant for thoracic epidural anesthesia and procedures targeting neuronal modulation of cardiac sympathetic innervation.

The cardiac autonomic nervous system (cANS) regulates cardiac adaptation to different demands. The heart is an asymmetrical organ, and in the selection of adequate treatment of cardiac diseases it may be relevant to take into account that the cANS also has sidedness as well as regional differences in anatomical, functional, and molecular characteristics. The left and right ventricles respond differently to adrenergic stimulation. Isoforms of nitric oxide synthase, which plays an important role in parasympathetic function, are also distributed asymmetrically across the heart. Treatment of cardiac disease heavily relies on affecting left-sided heart targets which are thought to apply to the right ventricle as well. Functional studies of the right ventricle have often been neglected. In addition, many principles have only been investigated in animals and not in humans. Anatomical and functional heterogeneity of the cANS in human tissue or subjects is highly valuable for understanding left- and right-sided cardiac pathology and for identifying novel treatment targets and modalities. Within this perspective, we aim to provide an overview and synthesis of anatomical and functional heterogeneity of the cANS in tissue or subjects, focusing on the human heart.

Cardiac sympathetic blockade with high-thoracic epidural anesthesia is considered beneficial in patients undergoing major surgery because it offers protection in ischemic heart disease. Major outcome studies have failed to confirm such a benefit, however. In fact, there is growing concern about potential harm associated with the use of thoracic epidural anesthesia in high-risk patients, although underlying mechanisms have not been identified. Since the latest review on this subject, a number of clinical and experimental studies have provided new information on the complex interaction between thoracic epidural anesthesia–induced sympatholysis and cardiovascular control mechanisms. Perhaps these new insights may help identify conditions in which benefits of thoracic epidural anesthesia may not outweigh potential risks. For example, cardiac sympathectomy with high-thoracic epidural anesthesia decreases right ventricular function and attenuates its capacity to cope with increased right ventricular afterload. Although the clinical significance of this pathophysiologic interaction is unknown at present, it identifies a subgroup of patients with established or pending pulmonary hypertension for whom outcome studies are needed. Other new areas of interest include the impact of thoracic epidural anesthesia–induced sympatholysis on cardiovascular control in conditions associated with increased sympathetic tone, surgical stress, and hemodynamic disruption. It was considered appropriate to collect and analyze all recent scientific information on this subject to provide a comprehensive update on the cardiovascular effects of high-thoracic epidural anesthesia and cardiac sympathectomy in healthy and diseased patients.

URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2844. Unique identifier: NTR2844.