Impaired Endothelin-1 Release in Tilt-Induced Syncope

Abstract

The neurohumoral events associated with neurocardiogenic syncope remain unclear. The simultaneous assessment of changes in endothelium-dependent and independent hormones and in autonomic balance in patients with tilt-induced syncope has been incompletely studied. Forty-six healthy subjects aged between 21 and 83 years (mean ± SEM 47 ± 3) underwent a 30-minute head-up tilt test at 60°. Fourteen subjects (10 females and 4 male subjects) exhibited syncope at 16 ± 2 minutes into the tilt. Hemodynamics were recorded every 5 minutes and blood samples for the measure of catecholamines, endothelin-1 (ET-1), and angiotensin-II (AT-II), were drawn at baseline, and 5, 10, 15, and 30 minutes into the tilt and immediately before syncope. Heart rate variability was analyzed by 5-minute segments during the test. Both catecholamines and ET-1 levels increased consistently in response to head-up tilt in subjects able to tolerate the test. Epinephrine increased to a greater extent before syncope. In contrast, ET-1 failed to increase at any time during the tilt and just before syncope. AT-II increased at 30 minutes into the tilt only in the control group. Finally, power in high-frequency bands decreased less in the group with syncope. Thus, compared with subjects able to tolerate a head-up tilt test, patients with syncope exhibit a greater increase in adrenomedullary activation, no significant increase in ET-1 levels, and a blunting in the decrease of vagal tone before syncope. The lack of increase in ET-1 during tilt may play a role in the inability to support orthostatic stress.