Ischemic modulation of myocardial innervation.

This article focuses on the interplay existing between the autonomic nervous system and the myocardium, with novel observations related to arrhythmogenesis. Myocardial ischemia and infarction produce an efferent denervation involving both limbs of the autonomic nervous system. As a consequence of the sympathetic denervation, the myocardial norepinephrine content is reduced to a major extent. As a logical consequence, this is followed by the phenomenon called "denervation supersensitivity", i.e. the tissue deprived of its nerve supply responds to the neural mediator in an exaggerated fashion. This is manifested by an exaggerated shortening of the effective refractory period during infusion of norepinephrine and by increased propensity for arrhythmias. With time, denervation is followed by reinnervation. An interesting counterpart of these findings is the possibility to document in patients after myocardial infarction if denervation has occurred using the MIBG technique. Not only efferent but also afferent denervation does occur and this might be involved in painless ischemia. In another series of studies we have provided the evidence that the pericardium is not a mere inert sac but it actively acts as a functional membrane. Pericardial prostaglandins released into the pericardial fluid alter electrophysiologic properties by modulating mostly the sympathetic effects; this may serve as a physiologic negative feedback control mechanism regulating sympathetic effects on the heart contributing to prevention of ischemic arrhythmias.