Orthostatic stress screening in healthy humans: differential adrenomedullary and noradrenergic responses in fainters versus non‐fainters

The concept of a “unitary sympathoadrenal response” to stress has evolved to the idea that adrenomedullary and sympathetic noradrenergic activation are not mutually exclusive which may affect orthostatic tolerance. We tested this hypothesis in an ongoing orthostatic screening protocol in healthy humans with no history of syncope. Following brachial artery catheter insertion and 20 min rest, 120 young adults (age 18–40) underwent head‐up tilt (HUT, 5 min supine, ≤5 min at 60°). Of these, 107 (Female/Male: 62/45, mean age ± SE: 26 ± 1) were categorized as non‐fainters while 13 (F/M: 10/3, age 23 ± 1) aborted due to impending syncope. Modelflow software estimated stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR). Arterial catecholamines were assayed during baseline and return‐to‐supine. Consistent with historical reports, the increase in epinephrine was greater in fainters than non‐fainters (344.9 ± 124 vs. 35.9 ± 4.0 pg/mL, p=0.03). However, the increase in norepinephrine was reduced in fainters vs. non‐fainters (109.5 ± 17.3 vs. 156.1 ± 7.5 pg/mL, p=0.05). Failure to maintain mean SVR and BP was present in fainters, while HR, SV, and CO were maintained until presyncope. This demonstrates that in healthy subjects with sudden and early intolerance to HUT, an exaggerated adrenomedullary response differentially accompanies a blunted noradrenergic response. NIH HL‐46493