Vagal Syncope Clinical Trial
Official title:
Circulating Biomarker(s) of Muscarinic Receptor Overexpression and Vagal Disorders.
Context
The investigators recently demonstrated a highly significant increase in muscarinic receptor
density in the myocardium of infants deceased from sudden infant death syndrome (SIDS)
compared to those of infants deceased from identified causes 1. Muscarinic receptor
overexpression was found in all SIDS samples studied to date. It was associated with an
average increase in acetylcholinesterase activity, appearing as a compensatory mechanism to
oppose the cardiac muscarinic receptor overexpression. Similar vago-cardiac abnormalities
were detected in a rabbit model of vagal hyperreactivity that the investigators first
described some years ago2. In these hyperreactive animals, expression of muscarinic receptors
was also enhanced in blood white cells. Noticeably, the pattern of changes in these cells
paralleled the pattern of changes in the heart. Thus, muscarinic abnormalities in cardiac
tissues could be inferred with high confidence from those measured in lymphocytes.This was
the first report of a vago-cardiac abnormality in sudden infant death syndrome. The
investigators findings also provided original and important perspectives for the
identification and therapeutic management of infants at risk of sudden death. As such, the
publication of the investigators work raised a major interest from the population and from
the scientific and medical communities, in particular cardio-pediatricians. ObjectivesThe
objective of the present clinical project is to validate, in human lymphocytes, muscarinic
receptor expression level (assessed by quantitative RT-PCR) as a circulating biomarker of
autonomic nervous system dysfunction and more specifically, of vagal hyperactivity and of
risk of sudden death. The project will include 2 major items, conducted in parallel:1.
evaluation of the muscarinic receptor expression in lymphocytes from adults with vagal
syncopes (n=60 patients from an existing file versus 60 controls) (Cardiology unit + Clinical
Investigation Centre (CIC) + Laboratory of Neurobiology and Cardiovascular Pharmacology); 2.
evaluation of the muscarinic receptor expression in lymphocytes from children with vagal
syncopes (n=60 versus 60 controls) (Pediatry unit + Clinical Investigation Centre +
Laboratory of Neurobiology and Cardiovascular Pharmacology).PerspectivesThis project
represents the first step of validation of a circulating marker of vagal hyperactivity and of
risk of SIDS in human. Once this step is completed, the investigators will start with the
prospective study " muscarinic receptor expression in lymphocytes and SIDS " (cord blood
collected at birth and follow up of the new-borns) (Maternity ward + CIC + Laboratory of
Neurobiology and Cardiovascular Pharmacology). Then therapeutic preventive management becomes
a realistic objective. A therapeutic clinical study will then be started with atropinic
drugs, in order to test their potential protective action against sudden death. The final
objective of the investigators research is the prevention of SIDS through i) identification -
as soon as birth - of new-borns at high risk and ii) appropriate prophylactic therapy. The
investigators work also opens exciting perspectives in the field of the still poorly
understood vagal disorders in children and adults such as vagal pauses.1 Livolsi et coll,
Plos One 5, e9464, 2010 ; 2 Livolsi et coll, Circulation 106, 2301-2304, 2002
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