Head-up tilt induced syncope and adenosine A2A receptor gene polymorphism.

AIMS: High adenosine plasma levels and high expression of adenosine A(2A) receptors are observed in patients with unexplained syncope and a positive head-up tilt test (HUT). This study aimed to evaluate the single nucleotide polymorphism (SNP) (c.1364 T>C) which is the most commonly found polymorphism in the A(2A) receptor gene, in patients with unexplained syncope undergoing HUT. METHODS AND RESULTS: One hundred and five patients with unexplained syncope who underwent HUT were included. Fifty-two had a positive test. Receptor genotype determinations were performed in patients and in 121 healthy subjects. Genotype (TT, CC, TC) was determined from DNA leucocytes. The distribution of the polymorphism showed significant (P < 0.0001) difference when the results of HUT were analysed. Fifty-two per cent of patients with a positive HUT had a CC genotype and 34.6% a TC genotype, whereas 13.2% of the patients with a negative HUT had a CC genotype and 71.7% a TC genotype. Patients with a CC genotype had a higher incidence of spontaneous syncopal episodes. CONCLUSION: In patients with unexplained syncope, a significant association between high incidence of syncopal episodes, positive HUT, and the presence of the CC variant in the adenosine A(2A) receptor gene was elicited.

Increased expression of adenosine A2A receptors in patients with spontaneous and head-up-tilt-induced syncope.

BACKGROUND: Adenosine may play a role in the triggering of neurocardiogenic syncope, but no information on adenosine receptors is available at the present time. OBJECTIVE: The purpose of this study was to investigate whether adenosine A2A receptors expression is altered in patients with neurocardiogenic syncope. METHODS: Adenosine plasma levels (APLs), the expression of A2A receptors, were measured (mean +/- standard error of the mean) during tilt testing. Expression of receptors was assessed on mononuclear cells using a selective receptor ligand. RESULTS: At baseline, the APLs of 16 patients with a positive test were higher than those of 17 patients with a negative test and of those of a control group (2.10 +/- 0.30 vs. 0.40 +/- 0.05 and 0.41 +/- 0.06 muM, respectively; P <.0001). The number of receptors was higher in patients tested positive than in patients tested negative or in the control group (122 +/- 10 vs. 38 +/- 4 and 44 +/- 4 fmol/g of proteins, respectively; P <.0001). No difference was found in the affinity or synthesis among the three groups. CONCLUSION: This study showed an increased number and an up-regulation of adenosine A2A receptors in patients with spontaneous syncope and a positive head-up tilt, which in the context of high APLs may play a role in the recurrence of syncopal episodes.

Role of endogenous adenosine as a modulator of syncope induced during tilt testing.

BACKGROUND: Previous reports that used head-up tilt testing and adenosine administration have suggested that adenosine may be an important endogenous mediator that may trigger a vasovagal response in susceptible patients. However, little is known regarding endogenous adenosine plasma levels (APLs) during vasovagal syncope provoked by tilt testing. The aim of this study was to determine whether APLs differ in patients with a positive head-up tilt test compared with those with a negative test and whether APLs are modified during tilt-induced vasovagal syncope. METHODS AND RESULTS: APLs (mean+/-SEM) were measured during head-up tilt test in 26 patients who presented with unexplained syncope. In the 15 patients with a negative test, APLs were 0.39+/-0.03 micromol/L at baseline, 0.22+/-0.03 micromol/L immediately after tilting, and 0.44+/-0.03 micromol/L after 45 minutes. APLs were significantly higher in the 11 patients with a positive test (2.66+/-0.67 micromol/L at baseline and 3.22+/-0.85 micromol/L immediately after tilting) than in those with a negative test. During tilt testing-induced syncope, APLs increased to reach 4.03+/-0.66 micromol/L (ie, a 52% increase compared with baseline levels; P<0.02). Furthermore, we observed that the higher the APL during syncope, the shorter the time to appearance of symptoms. CONCLUSIONS: This study showed that APLs were higher in patients with a positive tilt test than in patients with a negative test and that they increased during tilt testing-induced syncope. These observations suggest that adenosine release may be involved in the triggering mechanism of syncope induced during tilt testing.