Autonomic responses and neurohumoral control in the human early antenatal heart

Summary Previous sporadic findings and the results of recent, more systematic studies now permit us to make an attempt to outline the contribution of the sympathetic and parasympathetic system to the control of the human early antenatal cardiac function. In the developing heart of man, only acetylcholine and catecholamines have so far been proven to act as true autonomic transmitters. Muscariniccholinergic responses to acetylcholine and related agents can be detected from the 4th postconception week onwards, i.e. soon after the initiation of the first heartbeats. The same applies to the -adrenergic responsiveness to noradrenaline, adrenaline and other adrenergic stimulants in a somewhat later period, commencing at week 5 after conception. The maximum cardiac response to all these agonists becomes stronger as development continues. — Evidence is accumulating to suggest that prostaglandins and triiodothyronine might modulate the regulatory function of autonomic transmitters in the human early antenatal heart.Morphological and functional establishment of the autonomic innervation occurs in the human heart well after the appearance of the reactivity to autonomic transmitters. Under in vitro conditions, muscarinic-cholinergic neuro-effector transmission can be demonstrated in 10–12-week-old hearts, and cardiac -adrenergic transmission can first be detected in weeks 13–14. From these observations and from the appearance of the in utero fetal tachycardiac response to atropine in weeks 15–17 and the bradycardiac response to -blockers in weeks 23–28, it seems that the parasympathetic-cholinergic control of the developing human heart becomes functional and can play a role in the overall regulation of the antenatal cardiac function carlier than the sympathetic-adrenergic neural control. In the period before the onset of sympathetic neural control, the adrenergic regulation of the antenatal heart is achieved predominantly through the extra-adrenal (mainly the para-aortic) chromaffin tissues, whereas the co-operative function of the adrenal medulla becomes effective later in fetal life.