The Takotsubo Syndrome: Where the Sympathetic Stress Reflex and the Dive Reflex Conflict

Understanding of the pathophysiology of Takotsubo syndrome (TTS) remains incomplete. This is a hypothesis-driven editorial, proposing a new autonomic mechanism that may explain several important and puzzling features of TTS. Rather than involving a single reflex pathway, we suggest that TTS may result from the interaction and conflict of two evolutionarily conserved autonomic reflex responses. The first is the sympathetic stress response (SSR), a cardiovascular predominantly sympathomimetic reaction characterised by heightened adrenergic activity, tachycardia and cardiovascular stress. The second is the mammalian dive response (DR), a predominantly parasympathetic reflex characterised by bradycardia, peripheral vasoconstriction, and redistribution of blood flow to vital organs. Usually activated by facial wetting and afferent input through the trigeminal nerve, the DR may be initiated and certainly is moderated from the carotid bodies by way of the glossopharyngeal nerves. We propose that elements of both the SSR and the DR may be sequentially activated in TTS, producing both augmented and physiologically opposing autonomic effects. This model may help explain several recognised features of the syndrome, including the occurrence of dissecting aneurysms, particularly of the coronary arteries; the prominence of pulmonary congestion and dyspnoea; and the variability in pulse rate, with some patients presenting with bradycardia while others have tachycardia. Other aspects of the disorder remain unexplained, particularly why some persons are afflicted while others, suffering the same stress, remainsymptom-free. The TTS retains both its mystery and its evocative name.