Vasovagal syncope, sympathetic mechanisms and prognosis: the shape of things to come.

Vaddadi and co-workers, from the Baker Heart and Diabetes Research Institute of Melbourne, have examined, in a group of patients with a clinical history of recurrent postural vasovagal syncope, the behaviour of efferent postganglionic muscle sympathetic nerve traffic, directly assessed via the microneurographic technique in the peroneal nerve, during a fainting episode triggered by tilting. The background for this investigation is based on the hypothesis that neurally mediated syncope, and its related cardiovascular and neurohumoral alterations, has as a ‘primum movens’ the complete loss of sympathetic vasoconstrictor influences on the circulation (Figure 1). –7 This pathophysiological view appears to be supported by the evidence, collected during the past few years, that sympathetic neural outflow is almost completely withdrawn during a neurally mediated syncopal episode. 7 There are, however, two features of the neuroadrenergic responses to syncope that deserve to be highlighted. The first refers to the evidence that, despite the almost complete disappearance of the sympathetic neural discharge (so-called ‘neural silence’) reported during syncope, plasma norepinephrine and epinephrine concentrations, i.e. the adrenergic neurotransmitters, are only partially reduced in the blood reservoir. This implies that the hypothesis that neurogenic syncope might depend on an almost complete withdrawal of the neural adrenergic outflow to the circulation is not supported by the behaviour of the biochemical markers of adrenergic function. The second feature refers to the temporal patterns of the neural changes immediately preceding and accompanying vasovagal syncope. Indeed, there is evidence from previous studies that syncope-related sympathetic inhibition (indeed this was what previous studies have almost univocally reported) is preceded immediately before its appearance by a marked sympathetic activation, which parallels the decline in blood pressure triggered by the fainting episode. Only in a later stage of the syncope does the sympathetic inhibition reported by previous studies take place. How does the persistence of a normal sympathetic nerve firing pattern during syncope shown by Vaddadi and co-workers reconcile with the ‘neural silence’ observed in previous reports? –7 The authors have done their best in the Discussion to provide a sound answer to the above question. I would underline, as likely explanations, however, the following not mutually exclusive hypotheses. First, in many of the previous studies the reported ‘neural silence’ might have been in some way related to methodological problems, i.e. the loss of the sympathetic traffic signal during the syncope. This was not the case, however, in the report of Vaddadi et al., 1 in which in 10 out of the 16 patients examined the nerve recording site was fully maintained, allowing the persistence of a normal sympathetic activity during syncope to be shown. Secondly, the fact that in the study of Vaddadi et al. the recruited patients had a clinical history of vasovagal syncope, at variance from other studies, –7 allows the hypothesis to be advanced that the sympathetic neural responses to a fainting episode may be different according to the clinical history of recurrent vasovagal syncopes. This implies that the ‘neuroadrenergic profile’ of people suffering from vasovagal syncope may not necessarily be homogeneous and that factors such as the genetic background may be important for triggering such heterogeneous behaviour. In commenting on the results of the report by Vaddadi and coworkers, two other considerations should be taken into account. The first refers to the fact that the behaviour of sympathetic nerve traffic in the skeletal muscle area does not necessarily reflect the one seen in other districts. This has been shown, for example, in human obesity and in relation to the ageing process, in which some neural areas (the heart and the skin) do not display the same quantitative profile (sympathetic activation) reported in the muscle vascular area. The second consideration refers to