The role of the intrinsic cardiac nervous system in cardiac physiology and disease

It is well recognised that the complex neuronal hierarchy of the autonomic nervous system is important in the pathology of heart disease. In addition to the peripheral autonomic nerves, there is a dense network of intrinsic cardiac ganglia located at the level of the heart and acting as the final stage in the autonomic regulation of cardiac function. Understanding the role of this network in cardiac function could prove vital in understanding heart disease. The aims of this study were to characterise the topography and neurochemical phenotype of the rabbit intrinsic cardiac nervous system (ICNS) as well as to investigate the functional effects of electrical stimulation of intrinsic cardiac ganglia on the sinus and AV nodes. A coronary artery ligation heart failure model was used to examine the effects of myocardial infarction (MI) and heart failure (HF) on both the topography of the ICNS and the functional role of the ICNS. Histochemical staining revealed an intricate network of nerves and ganglia located primarily on the heart hilum. Significant neuronal remodelling was evident following MI, with the enlargement of somata within ganglia that are known to preferentially innervate the ventricles. Heart rate changes occurred primarily as a result of stimulation of ganglia within the right atrial (RA) and right neuronal cluster (RNC) regions. MI resulted in exaggerated bradycardic responses during stimulation of the RA and RNC regions, accompanied by a significant increase in tachycardia responses during stimulation of ganglia within the RA and RNC. In conclusion, it is becoming increasingly evident that the ICNS is a key network in the cardiac neuronal hierarchy. The ability of the ICNS to function both in normal physiology and also to adapt following MI and HF suggests that the ICNS could be a significant potential therapeutic target for the prevention and treatment of cardiac disease.