Hemodynamics of orthostatic intolerance: implications for gender differences

Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, and the University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75231 Submitted 22 August 2002 ; accepted in final form 26 September 2003 Women have a greater incidence of orthostatic intolerance than men. We hypothesized that this difference is related to hemodynamic effects on regulation of cardiac filling rather than to reduced responsiveness of vascular resistance during orthostatic stress. We constructed Frank-Starling curves from pulmonary capillary wedge pressure (PCWP), stroke volume (SV), and stroke index (SI) during lower body negative pressure (LBNP) and saline infusion in 10 healthy young women and 13 men. Orthostatic tolerance was determined by progressive LBNP to presyncope. LBNP tolerance was significantly lower in women than in men (626.8 ± 55.0 vs. 927.7 ± 53.0 mmHg x min, P < 0.01). Women had steeper maximal slopes of Starling curves than men whether expressed as SV (12.5 ± 2.0 vs. 7.1 ± 1.5 ml/mmHg, P < 0.05) or normalized as SI (6.31 ± 0.8 vs. 4.29 ± 0.6 ml·m –2 ·mmHg –1 , P < 0.05). During progressive LBNP, PCWP dropped quickly at low levels, and reached a plateau at high levels of LBNP near presyncope in all subjects. SV was 35% and SI was 29% lower in women at presyncope (both P < 0.05). Coincident with the smaller SV, women had higher heart rates but similar mean arterial pressures compared with men at presyncope. Vascular resistance and plasma norepinephrine concentration were similar between genders. We conclude that lower orthostatic tolerance in women is associated with decreased cardiac filling rather than reduced responsiveness of vascular resistance during orthostatic challenges. Thus cardiac mechanics and Frank-Starling relationship may be important mechanisms underlying the gender difference in orthostatic tolerance. orthostatic hypotension; stroke volume; vascular resistance; pulmonary capillary wedge pressure; lower body negative pressure Address for reprint requests and other correspondence: B. D. Levine, Institute for Exercise and Environmental Medicine, 7232 Greenville Ave., Suite 435, Dallas, TX 75231 (E-mail: BenjaminLevine{at}texashealth.org ).