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 μmol/L at baseline, 0.22±0.03 μmol/L immediately after tilting, and 0.44±0.03 μmol/L after 45 minutes. APLs were significantly higher in the 11 patients with a positive test (2.66±0.67 μmol/L at baseline and 3.22±0.85 μmol/L immediately after tilting) than in those with a negative test. During tilt testing–induced syncope, APLs increased to reach 4.03±0.66 μmol/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.