The Study of Sex Differences in the Regulation of Orthostatic Blood Pressure: the Role of the Splanchnic Circulation
Open Access
- Author:
- Jarvis, Sara
- Graduate Program:
- Kinesiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- March 25, 2009
- Committee Members:
- James Anthony Pawelczyk, Dissertation Advisor/Co-Advisor
James Anthony Pawelczyk, Committee Chair/Co-Chair
Cynthia J Bartok, Committee Member
Mosuk Chow, Committee Member
David Nathan Proctor, Committee Member
Nancy Williams, Committee Member - Keywords:
- blood pressure regulation
splanchnic blood flow
bioelectrical impedance
orthostatic intolerance
somatostatin analog
lower body negative pressure - Abstract:
- Previous investigations have shown that women are less orthostatically tolerant than men. Several mechanisms have been proposed; however, the exact mechanism has not been defined. Blood volume distribution to high capacitance areas (i.e., the splanchnic region) influence orthostatic tolerance. Limited data suggests that the distribution of blood volume during an orthostatic stress differs between women and men, where the women tend to pool more blood in the lower abdomen/pelvic region. Accordingly, this series of experiments was designed to examine blood pressure regulation differences between the sexes as it relates to the contribution of the splanchnic circulation. In the first study, we sought to clarify whether or not a sex difference existed in tilt table tolerance. We hypothesized that during head-up tilt (HUT) women would demonstrate less splanchnic vasoconstriction, leading to splanchnic pooling, lower blood pressure, and lower orthostatic tolerance. Mean arterial blood pressure (MAP), heart rate (HR), cardiac output (Qc, C2H2 rebreathing), stroke volume, splanchnic blood flow (SpBF, indocyanine green clearance), and vascular conductance (systemic, SVC=Qc/MAP; splanchnic, SpVC=SpBF/MAP; non-splanchnic, non-SpVC=SVC-SpVC) were measured during supine baseline, 70° HUT, and recovery in 14 healthy women (23±6 yrs; mean±SD) and 16 men (23±5 yrs). Neither median tilt time (15.7 vs. 21.8 min; ÷2=0.54, p=0.46), nor the proportion surviving 45 min of HUT (÷2=2.92, p=0.09) was different between the sexes. MAP was lower in women (supine: 77±5 vs. 86±9 mmHg, p<0.01; tilt: 72±8 vs. 83±10 mmHg, p<0.01), while HR and cardiac index were not different between the sexes (supine: 66±6 vs. 64±8 bpm; tilt: 96±13 vs. 94±10 bpm; supine: 3.8±0.9 vs. 3.7±0.7 L•min-1•m-2; tilt: 2.7±0.8 vs. 2.3±0.5 L•min-1•m-2). SpBF and SpVC were lower in women at rest but not during tilt (SpBF, supine: 1174±243 vs. 1670±391 ml/min, p<0.01; SpVC, supine: 14.83±3.61 vs. 19.59±4.95 ml•min-1•mmHg-1, p<0.01; SpBF, tilt: 884±300 vs. 1094±271 ml/min; SpVC, tilt: 13.14±4.28 vs. 14.82±4.16 ml•min-1•mmHg-1). However, in the women SpVC was not reduced between baseline and tilt (∆SpVC: -1.70±3.19 ml•min-1•mmHg-1, p=NS; -4.81±3.44 ml•min-1•mmHg-1, p<0.01), suggesting a blunted vasoconstrictor response. Thus, women tended to have lower tilt-table tolerance associated with a smaller splanchnic vasoconstrictor reserve than men. In the second study, splanchnic hemodynamics and tilt table tolerance were assessed after an infusion of placebo or octreotide acetate, a somatostatin analog whose vascular effects are largely confined to the splanchnic circulation. We hypothesized that reductions in splanchnic blood flow (SpBF) and splanchnic vascular conductance (SpVC) would be related to improvements in tilt time. Hemodynamic variables were collected in 14 women and 16 men during baseline, 70° head-up tilt (HUT), and recovery during placebo and octreotide conditions. HUT elicited an increase in heart rate and decreases in mean arterial pressure, cardiac index, stroke index, and systemic vascular conductance (SVC). Additionally, SpVC and non-SpVC were lower during HUT. Octreotide reduced SpBF and SpVC and increased SVC and non-SpVC. A repeated measures ANOVA was used to compare changes from baseline with respect to sex and condition. Changes in SpBF and SpVC between supine and HUT were smaller in women (p<0.05). There was a significant improvement in tilt table tolerance in both sexes with octreotide administration. Median tilt times were increased from 15.7 and 21.8 min to 37.0 and 45.0 min for women and men, respectively. A significant relationship existed between ∆SpBF (placebo-octreotide) and ∆tilt time in women (∆tilt time=2.5-0.0083 ∆SpBF, p=0.0051) but not men (∆tilt time=3.41–0.0008 ∆SpBF, p=0.59). Thus, administration of octreotide acetate improved tilt table tolerance where the principal mechanism was by decreasing splanchnic vascular conductance. The purpose of the third study was to quantify blood volume redistribution during graded tilt. Head-up tilt (HUT) redistributes ~700 mL of blood to the dependent regions. In a gravitational field, hydrostatic pressure is balanced against vascular compliance, resulting in a hydrostatic indifferent point (HIP). Its location is independent of posture and should be coincident with a volume indifferent point (VIP). Cardiac filling is determined by the hydrostatic gradient between the HIP/VIP and right atrium. A more inferior VIP would lead to decreased preload and possibly orthostatic intolerance. We located the VIP by employing segmental impedance to examine blood volume redistribution during HUT. During HUT impedance increased above and decreased below the VIP, respectively, due to blood volume shifts. An exponential model related blood volume shifts and the hydrostatic gradient to determine the location of the VIP, which was located at 64.5±2.6% of an individual’s height. This method may provide a quantitative framework to assess the effects of blood volume distribution on tilt tolerance. The fourth and fifth studies examined the impact of splanchnic blood volume manipulation on the location of the VIP. We previously indentified that the splanchnic circulation contributes to the location of the VIP. Using segmental impedance we identified the VIP under control conditions and when blood volume within the splanchnic segment was altered. We also sought to determine the relationship between the location of the VIP and an individual’s tolerance to an orthostatic stress. In Protocol 1, we found that administration of the somatostatin analog, octreotide acetate, a selective splanchnic vasoconstrictor, induced a superior shift in the location of the VIP (+1.9±3.3 cm, p=0.03). This finding substantiated previous reports of improvements in tilt tolerance after octreotide and suggests it might be related to relocation of the VIP. Conversely, in Protocol 2, exposure to lower body negative pressure (LBNP) induced splanchnic pooling and moved the VIP inferiorly (-6.0±7.2 cm, p<0.01). LBNP combined with head-up tilt significantly decreased tilt table tolerance (median tilt times: 28.0 min vs. 4.2 min; ÷2=14.29, p<0.01); a positive relationship between ÄVIP and Ätilt time existed (Ätilt time = 3.05 + 0.12 ÄVIP, p=0.03). Thus, individuals that demonstrated the largest inferior shift in the location of the VIP also demonstrated the largest decrease in tilt table tolerance. We conclude that the splanchnic circulation plays an important role in determining the location of the VIP and its location is a determinant of tolerance to an orthostatic stress. The results of these studies indicate that women and men regulate blood pressure differently in the upright posture. Specifically, women showed a decreased vasoconstrictor response that could be isolated to the splanchnic circulation. Administration of octreotide, a selective splanchnic vasoconstrictor, improved blood pressure regulation during head-up tilt. The mechanism by which this occured was related to alteration of the volume indifferent point to a more superior location. Conversely, decrements in tilt table tolerance were shown to be directly related to an inferior shift in the location of the volume indifferent point.