Expression of muscarinic receptors in adults and children with severe vagal syncope

Abstract

Syncope is an ordinary reason for consultation in cardiac units. Vagal etiology is frequently mentioned but many additional tests are often proposed to exclude other causes. Overexpression of muscarinic M 2 receptors (M 2 R) was observed in the myocardium and blood of a model of rabbits with vagal hyperreactivity, then in the hearts of newborns deceased from sudden infant death syndrome and recently in the blood of infants who experienced severe idiopathic apparent life threatening events (iALTE). We investigated M2R and acetylcholinesterase (AchE) expressions in the blood of adults and children who experienced severe vagal syncope. A total of 151 subjects were prospectively enrolled in a multicenter, comparative study. Fifty-five adults and 43 children ages 1 to 18, exhibiting severe and repeated vagal syncope, were compared to 53 healthy matched controls. Total mRNA was blindly extracted from all blood samples and reverse transcribed into cDNA. M2R and AchE expressions were measured by RT-qPCR. M 2 R expression was distinctively higher in the vagal group ( n = 98) as compared to controls ( n = 53) (median 0.923 vs. 0.238, P = 0.0006). Similarly AchE level was higher in the vagal group than in controls (median 0.796 vs. 0.423, P = 0.0078). Perforce, the ratio M 2 R/AchE was strongly higher in the vagal group than in controls (median 1.083 vs. 0.79, P = 0.0056). M2R and AchE overexpression was shown in the blood of adults and children exhibiting severe vagal syncope compared to controls. AchE overexpression seems to an adaptive reaction, not fully mature in children. M2R overexpression could be a simple blood biomarker of vagal syncope and help in the assessment of faintness. Further, these results may suggest a continuum between iALTE in infants and vagal syncope in both children and adults, with a muscarinic common feature. Larger studies are needed to confirm this biomarker's potential and to evaluate the clinical implications.