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Sympathetic activation during orthostatic stress is accompanied by a marked increase in low-frequency (LF, approximately 0.1-Hz) oscillation of sympathetic nerve activity (SNA) when arterial pressure (AP) is well maintained. However, LF oscillation of SNA during development of orthostatic neurally mediated syncope remains unknown. Ten healthy subjects who developed head-up tilt (HUT)-induced syncope and 10 age-matched nonsyncopal controls were studied. Nonstationary time-dependent changes in calf muscle SNA (MSNA, microneurography), R-R interval, and AP (finger photoplethysmography) variability during a 15-min 60 degrees HUT test were assessed using complex demodulation. In both groups, HUT during the first 5 min increased heart rate, magnitude of MSNA, LF and respiratory high-frequency (HF) amplitudes of MSNA variability, and LF and HF amplitudes of AP variability but decreased HF amplitude of R-R interval variability (index of cardiac vagal nerve activity). In the nonsyncopal group, these changes were sustained throughout HUT. In the syncopal group, systolic AP decreased from 100 to 60 s before onset of syncope; LF amplitude of MSNA variability decreased, whereas magnitude of MSNA and LF amplitude of AP variability remained elevated. From 60 s before onset of syncope, MSNA and heart rate decreased, index of cardiac vagal nerve activity increased, and AP further decreased to the level at syncope. LF oscillation of MSNA variability decreased during development of orthostatic neurally mediated syncope, preceding sympathetic withdrawal, bradycardia, and severe hypotension, to the level at syncope.

Although orthostatic hypotension is a common clinical syndrome after spaceflight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), the pathophysiology remains unclear. The authors' hypothesis that a decrease in sympathetic nerve activity is the major pathophysiology underlying orthostatic hypotension after HDBR was tested in a study involving 14-day HDBR in 22 healthy subjects who showed no orthostatic hypotension during 15-min 60 degrees head-up tilt test (HUT) at baseline. After HDBR, 10 of 22 subjects demonstrated orthostatic hypotension during 60 degrees HUT. In subjects with orthostatic hypotension, total activity of muscle sympathetic nerve activity (MSNA) increased less during the first minute of 60 degrees HUT after HDBR (314% of resting supine activity) than before HDBR (523% of resting supine activity, P < 0.05) despite HDBR-induced reduction in plasma volume (13% of plasma volume before HDBR). The postural increase in total MSNA continued during several more minutes of 60 degrees HUT while arterial pressure was maintained. Thereafter, however, total MSNA was paradoxically suppressed by 104% of the resting supine level at the last minute of HUT (P < 0.05 vs. earlier 60 degrees HUT periods). The suppression of total MSNA was accompanied by a 22 +/- 4-mmHg decrease in mean blood pressure (systolic blood pressure <80 mmHg). In contrast, orthostatic activation of total MSNA was preserved throughout 60 degrees HUT in subjects who did not develop orthostatic hypotension. These data support the hypothesis that a decrease in sympathetic nerve activity is the major pathophysiological factor underlying orthostatic hypotension after HDBR. It appears that the diminished sympathetic activity, in combination with other factors associated with HDBR (e.g., hypovolemia), may predispose some individuals to postural hypotension.

Respiratory sinus arrhythmia (RSA) may improve the efficiency of pulmonary gas exchange by matching the pulmonary blood flow to lung volume during each respiratory cycle. If so, an increased demand for pulmonary gas exchange may enhance RSA magnitude. We therefore tested the hypothesis that CO2 directly affects RSA in conscious humans even when changes in tidal volume (V(T)) and breathing frequency (F(B)), which indirectly affect RSA, are prevented. In seven healthy subjects, we adjusted end-tidal PCO2 (PET(CO2)) to 30, 40, or 50 mmHg in random order at constant V(T) and F(B). The mean amplitude of the high-frequency component of R-R interval variation was used as a quantitative assessment of RSA magnitude. RSA magnitude increased progressively with PET(CO2) (P < 0.001). Mean R-R interval did not differ at PET(CO2) of 40 and 50 mmHg but was less at 30 mmHg (P < 0.05). Because V(T) and F(B) were constant, these results support our hypothesis that increased CO2 directly increases RSA magnitude, probably via a direct effect on medullary mechanisms generating RSA.

Respiratory sinus arrhythmia (RSA) may serve to enhance pulmonary gas exchange efficiency by matching pulmonary blood flow with lung volume within each respiratory cycle. We examined the hypothesis that RSA is augmented as an active physiological response to hypercapnia. We measured electrocardiograms and arterial blood pressure during progressive hypercapnia in conscious dogs that were prepared with a permanent tracheostomy and an implanted blood pressure telemetry unit. The intensity of RSA was assessed continuously as the amplitude of respiratory fluctuation of heart rate using complex demodulation. In a total of 39 runs of hypercapnia in 3 dogs, RSA increased by 38 and 43% of the control level when minute ventilation reached 10 and 15 l/min, respectively (P < 0.0001 for both), and heart rate and mean arterial pressure showed no significant change. The increases in RSA were significant even after adjustment for the effects of increased tidal volume, respiratory rate, and respiratory fluctuation of arterial blood pressure (P < 0.001). These observations indicate that increased RSA during hypercapnia is not the consequence of altered autonomic balance or respiratory patterns and support the hypothesis that RSA is augmented as an active physiological response to hypercapnia.