YOHIMBINE IN NEURALLY-MEDIATED SYNCOPE - PATHOPHYSIOLOGICAL IMPLICATIONS

In this study, we evaluated if increased sympathetic stimulation is an essential requirement for the development of neurally mediated syncop e (NMS) by manipulating overall sympathetic outflow in subjects suscep tible to tilt-induced syncope. Eight previously characterized patients with recurrent NMS (five females and three males; 34+/-2 yr) were rec ruited from the Vanderbilt Syncope Unit and eight age-matched controls underwent,initial administration of clonidine (CLO) or yohimbine (YHO ). This was done, prospectively, to determine doses of these agents th at would increase or decrease plasma norepinephrine levels by greater than or equal to 30%. On a different day, in all subjects we-determine d intraarterial blood pressure, EKG and muscle sympathetic nerve activ ity (MSNA) both supine and during upright tilt. After this, subjects r andomly received either CLO or YHO, and 3 h later another tilt was per formed. After 1 wk, a similar procedure with the other drug was perfor med. During the two basal tilts, all the control subjects completed th e study, whereas all the NMS patients developed syncope. Reduction in sympathetic tone by CLO resulted in a decreased tolerance to tilt in t hree out of eight controls and in all the NMS patients. In contrast, Y HO not only increased basal plasma NorEpi levels and MSNA, but also pr evented syncope in seven out of eight patients. In a selected populati on of patients, increased sympathetic activity is not a prerequisite f or the development of syncope. Yohimbine-induced enhancement of sympat hetic tone in patients with NMS improves orthostatic tolerance and rai ses the possibility that this drug may be a useful agent in the treatm ent of NMS.