This thesis comprises of four experiments from which related but independent analyses were undertaken. The interventions employed were designed to investigate the effect of cardiovascular adaptation, both in the short and long term on the cardiovascular responses to orthostatic stress. The first study, described in Chapter 3, tested the hypothesis that the cardiovascular system (CVS) could adapt to repeated orthostatic challenges in a single session. 14 subjects were exposed to ten +75° head-up tilts (HUT) over 70 mins. Each tilt involved a 5 min supine period (SUPINE) followed by 2 min HUT (TILT). Various indices of cardiovascular function were determined non-invasively. Cardiovascular responses to HUT10 for the final 30s of SUPINE and the first 30s of TILT were compared with those of HUT1. Integrated cardiac baroreflex sensitivity (BRS) was assessed using the Valsalva Manoeuvre (VM). Results showed MAP and DBP increased in both SUPINE (MAP p=0.009, DBP p=0.002) and TILT (MAP p=0.003, DBP p=0.009) for HUT10 compared with HUT1. TPR increased during TILT only (p=0.001) during HUT10 compared with HUT1. CO and SV were decreased during SUPINE at HUT10 relative to HUT1, however, there were no differences in TILT at HUT10 for either CO or SV. There was no change in the response of BRS, HR or SBP from HUT1 to HUT10. This study indicated that 10 repetitive HUTs can elicit changes in the cardiovascular responses to orthostasis, reflected by an increased TPR. The second study, described in Chapter 4, investigated the effect of the repeated HUT protocol outlined above on the cardiovascular responses to the squat-stand test (SST). 16 subjects were randomly allocated into either a tilting group that underwent ten +75° HUTs in 70 min (TILTING) or a control group that underwent 70 min of rest (CONTROL). Before and after the 70 min of either HUT or rest, subjects performed a SST (SST1 and SST2 respectively). The same cardiovascular parameters as those used in Chapter 3 were determined during both SSTs. The final 30s of SQUAT and the first 30s of STAND (divided into three 10-sec blocks termed STAND10, STAND20 and STAND30) were compared between SST1 and SST2, results were as follows. TILTING: during the SQUAT phase of SST2, SBP, MAP, DBP and TPR were significantly elevated (p less than 0.05) and HR was significantly decreased (p=0.032) compared with SST1; at STAND10, DBP and MAP were significantly increased (p less than 0.05); at STAND20, SBP was increased (p=0.03); and, at STAND30, DBP, SBP and MAP (p less than 0.05) were increased. There were no differences observed between SST1 and SST2 in the CONTROL group. Results indicated that ten consecutive +75° HUTs can improve the CVS responses to the SST. This is predominantly due to an increase in DBP, indicative of a change in vascular resistance. The third study, outlined in Chapter 5, investigated the effect of lower limb unilateral and bilateral resistance exercise on the blood pressure (BP) and HR responses in young males. 12 normotensive, sedentary young males were divided into 2 groups; one group exercised unilaterally and the other bilaterally. Thirty seconds of resting data were collected before subjects performed 4 SETs of 10-12 reps on a seated leg press. SET 1 was performed at 50% of 10-12RM, SET 2 was performed at 75% and SET 3 and SET 4 were performed at 10- 12RM. Bilateral resistance exercise elicited greater increases in SBP than unilateral exercise at SETs 2, 3 and 4 (p less than 0.05). DBP was only greater with bilateral exercise relative to unilateral exercise at SET 2 (p=0.036). There were no differences between the groups for the HR response. This study demonstrated that the BP response to bilateral lower limb resistance exercise was significantly greater than that of unilateral exercise in young sedentary males. This information could be beneficial to many populations for whom lower BP responses to exercise would be an advantage. Following on from this, to investigate long term improvements in cardiovascular responses to orthostasis the study outlined in Chapter 6, investigated the effect of acute (10 weeks) and chronic (more than 4 years) resistance training (RT) on the cardiovascular responses to both HUT and SST. 22 young males were allocated into three groups. The UNILATERAL (N=7) and the BILATERAL (N=7) groups performed baseline testing followed by 10 weeks of lower limb RT (performed unilaterally or bilaterally), followed by repeats of the tests performed at baseline. The CONTROL group (N=8) followed the same protocol except they were asked to perform no resistance training during the 10 weeks between testing sessions. An additional 7 subjects were allocated to a CHRONIC group consisting of individuals who had been training for more than 4 years. These subjects only performed the baseline testing. Baseline testing consisted of a number of cardiovascular tests, ultrasound for vein diameter, BRS via VM, and tests for calf ejection fraction and venous elasticity. Results demonstrated that neither unilateral nor bilateral RT caused an alteration in the cardiovascular response to the HUT or SST. There were no changes in any cardiovascular variable in response to acute RT relative to the control group. The CHRONIC group had a decreased cardiovascular response to both orthostatic challenges, with a decrease in SV in response to HUT being greater in the chronic group relative to the other groups (p less than 0.05) and the TPR response to SST being significantly less than the control group (p less than 0.05). The CHRONIC group also had a smaller elastic modulus for the right leg in comparison to the other groups (p less than 0.05). Results indicate that heavy resistance exercise may cause a decreased cardiovascular response to orthostatic stress and that these decreases may be controlled by a decreased venous elasticity. Collectively, these results demonstrate that the CVS is highly adaptable to repeated orthostatic stress and the dominant underlying feature of this protective adaptation is increased vascular resistance. Following the repeated HUT the CVS is in a more protected state and has become better able to defend itself against the adverse consequences of rapidly applied hydrostatic force. However lower limb RT performed bilaterally (with large increases in BP) or unilaterally (with lower increases in BP) does not improve CVS response to orthostatic stress, in fact chronic RT (more than 4 yrs) appears to impair the CVS response to orthostasis, potentially due to decreased venous elasticity.

Young women are known to exhibit a greater incidence of orthostatic hypotension than men. The exact mechanisms for this are unclear and it has been proposed to be related to cardiac filling, peripheral resistance, and/or regional blood pooling. The sexually dimorphic effects of lower body negative pressure (LBNP) or upright posture were investigated throughout this study. Women could experience these changes due to effects of the sex hormones estrogen and progesterone. Chapters 3 and 4 in this thesis investigated the responses of women to LBNP in both the follicular and the luteal phase of the menstrual cycle (and age-matched men). Women at these points of the cycle have approximately equal levels of estrogen with high levels of progesterone in the luteal phase. Furthermore, Chapter 5 investigated the responses of pre-menopausal and post-menopausal women (and age-matched men) to sitting and standing. These studies will help to explain the effects of female sex hormones on cardiovascular responses to simulated or real orthostatic stress. LBNP simulates an orthostatic stress by causing a caudal fluid shift and was used in Chapters 3 and 4 as a stimulus to optimize the position of the participants for cardiovascular measurements. A supine-to-sit-to-stand test (i.e. actual orthostatic stress) was used in Chapter 5 as a stimulus. Head-down bed-rest (HDBR) is a model used to simulate microgravity and induces a fluid shift away from the legs towards the head. It has been shown to augment the responses to LBNP and was thus used to enhance the cardiovascular and hormonal responses of men and women to LBNP. A seated control (SEAT) was also used in an attempt to control for the equivalent period of inactivity and circadian rhythm. Blood pressure responses to LBNP were not different between menstrual phases although the physiological mechanisms may be somewhat different. Women in the luteal phase had higher portal vein resistance index which would contribute to moving splanchnic blood pools to maintain venous return during an orthostatic stress. When comparing women in the follicular phase to men, there was a decrease of blood pressure in women during LBNP which was not observed in men. This decrease was likely a result of reduced venous return as evidenced by a greater loss of central venous pressure and a greater increase of thoracic impedance during LBNP. This could have been a result of 1) splanchnic blood pooling in women as men had a greater increase of portal vein resistance index during LBNP, and/or 2) attenuated activation of the renin-angiotensin-aldosterone pathway in women during LBNP. After considering the effects of circadian rhythm and inactivity in all participants, HDBR resulted in 1) higher heart rate with a greater increase during LBNP, 2) a greater decrease of stroke volume during LBNP, 3) a greater increase of thoracic impedance during LBNP, 4) smaller inferior vena cava diameter, 5) lower norepinephrine, and 6) lower blood volume. These changes indicate that after 4-hours of HDBR resting venous return and venous return during LBNP was lower in all participants. However, the mechanisms by which each sex or menstrual phase responded were different. After HDBR men had higher pelvic impedance, higher vasopressin, and higher endothelin-1 compared to women in the follicular phase. After HDBR women in the luteal phase also had higher vasopressin and higher pelvic impedance compared to women in the follicular phase. During the supine-to-sit-to-stand protocol young women (follicular phase) exhibited a greater increase of heart rate during the 3rd minute of each posture likely due to reduced stroke volume compared to young men and post-menopausal women. During the transitions to sitting or standing young women also had an impaired ability to maintain stroke volume and cardiac output compared to post-menopausal women and age-matched men. These results imply that young women had lower venous return than older women and age-matched men during an orthostatic stress. In comparison to older men, post-menopausal women also had slightly reduced venous return, but the difference was smaller than that seen in the younger groups. There were no differences in middle cerebral artery blood flow velocity when comparing younger and older groups of men and women. The results of this investigation have outlined how men respond to an orthostatic stress differently than women (i.e. via a decrease in splanchnic pooling and a greater increase of vasoconstrictors), and have helped to outline a role for female sex hormones in the cardiovascular responses to an orthostatic stress (i.e. post-menopausal women exhibit greater venous return during an orthostatic stress compared to younger cycling women).

Many senescent individuals demonstrate an inability to regulate mean arterial pressure (MAP) in response to standing or head-up tilt; however, whether this aging effect is the result of depressed cardiac function or an inability to reduce peripheral vascular conductance remains unknown. Therefore, the purpose of this research was to investigate the effects of aging on MAP, heart rate (HR), regional blood flow (via radioactive-microspheres), and vascular conductance during head-up tilt in conscious young (4 mo; n=12) and old (24 mo; n=10) male Fischer-344 rats. Heart rate and MAP were measured continuously during normal posture and during 10 minutes of head-up tilt. Blood flow was determined during normal posture and at the end of 10 minutes of head-up tilt. Young rats increased MAP significantly at the onset of head-up tilt and generally maintained the increase in MAP for the duration of head-up tilt, while aged rats showed a significant reduction in MAP after 10 minutes of head-up tilt. In the normal posture, aged rats demonstrated lower blood flow to splanchnic, bone, renal, and skin tissues versus young rats. With tilt there were decreases in blood flow to skin, bone, and hind-limb in both age groups and in fat, splanchnic, reproductive, and renal tissues in the young. Bone blood flow was attenuated with age across both conditions in hind foot, distal femur, femur marrow, and proximal and distal tibia. Head-up tilt caused a decrease in blood flow across both age groups in all bones sampled with the exception of the hind foot. These results provide evidence that the initial maintenance of MAP in aged rats during head-up tilt occurs through decreased regional blood flow and vascular conductance, and that the fall in pressure is not attributable to an increase in tissue blood flow and vascular conductance. Therefore, reductions in arterial pressure during headup tilt are likely a result of an old age-induced reduction in cardiac performance. In addition, this is the first study to demonstrate a decreased bone vascular conductance in both young and old rats during head-up tilt.

Young women are known to exhibit a greater incidence of orthostatic hypotension than men. The exact mechanisms for this are unclear and it has been proposed to be related to cardiac filling, peripheral resistance, and/or regional blood pooling. The sexually dimorphic effects of lower body negative pressure (LBNP) or upright posture were investigated throughout this study. Women could experience these changes due to effects of the sex hormones estrogen and progesterone. Chapters 3 and 4 in this thesis investigated the responses of women to LBNP in both the follicular and the luteal phase of the menstrual cycle (and age-matched men). Women at these points of the cycle have approximately equal levels of estrogen with high levels of progesterone in the luteal phase. Furthermore, Chapter 5 investigated the responses of pre-menopausal and post-menopausal women (and age-matched men) to sitting and standing. These studies will help to explain the effects of female sex hormones on cardiovascular responses to simulated or real orthostatic stress. LBNP simulates an orthostatic stress by causing a caudal fluid shift and was used in Chapters 3 and 4 as a stimulus to optimize the position of the participants for cardiovascular measurements. A supine-to-sit-to-stand test (i.e. actual orthostatic stress) was used in Chapter 5 as a stimulus. Head-down bed-rest (HDBR) is a model used to simulate microgravity and induces a fluid shift away from the legs towards the head. It has been shown to augment the responses to LBNP and was thus used to enhance the cardiovascular and hormonal responses of men and women to LBNP. A seated control (SEAT) was also used in an attempt to control for the equivalent period of inactivity and circadian rhythm. Blood pressure responses to LBNP were not different between menstrual phases although the physiological mechanisms may be somewhat different. Women in the luteal phase had higher portal vein resistance index which would contribute to moving splanchnic blood pools to maintain venous return during an orthostatic stress. When comparing women in the follicular phase to men, there was a decrease of blood pressure in women during LBNP which was not observed in men. This decrease was likely a result of reduced venous return as evidenced by a greater loss of central venous pressure and a greater increase of thoracic impedance during LBNP. This could have been a result of 1) splanchnic blood pooling in women as men had a greater increase of portal vein resistance index during LBNP, and/or 2) attenuated activation of the renin-angiotensin-aldosterone pathway in women during LBNP. After considering the effects of circadian rhythm and inactivity in all participants, HDBR resulted in 1) higher heart rate with a greater increase during LBNP, 2) a greater decrease of stroke volume during LBNP, 3) a greater increase of thoracic impedance during LBNP, 4) smaller inferior vena cava diameter, 5) lower norepinephrine, and 6) lower blood volume. These changes indicate that after 4-hours of HDBR resting venous return and venous return during LBNP was lower in all participants. However, the mechanisms by which each sex or menstrual phase responded were different. After HDBR men had higher pelvic impedance, higher vasopressin, and higher endothelin-1 compared to women in the follicular phase. After HDBR women in the luteal phase also had higher vasopressin and higher pelvic impedance compared to women in the follicular phase. During the supine-to-sit-to-stand protocol young women (follicular phase) exhibited a greater increase of heart rate during the 3rd minute of each posture likely due to reduced stroke volume compared to young men and post-menopausal women. During the transitions to sitting or standing young women also had an impaired ability to maintain stroke volume and cardiac output compared to post-menopausal women and age-matched men. These results imply that young women had lower venous return than older women and age-matched men during an orthostatic stress. In comparison to older men, post-menopausal women also had slightly reduced venous return, but the difference was smaller than that seen in the younger groups. There were no differences in middle cerebral artery blood flow velocity when comparing younger and older groups of men and women. The results of this investigation have outlined how men respond to an orthostatic stress differently than women (i.e. via a decrease in splanchnic pooling and a greater increase of vasoconstrictors), and have helped to outline a role for female sex hormones in the cardiovascular responses to an orthostatic stress (i.e. post-menopausal women exhibit greater venous return during an orthostatic stress compared to younger cycling women).

No description available.

Thesis (MPhysio)--University of South Australia, 1998

Academisch Proefschrift--Universiteit van Amsterdam, 2007. / Includes bibliographical references (p. 91-108).

Thesis (M.S.)--University of Michigan, 1972.

Thesis (M.S.)--University of Michigan, 1972.

Purpose: This study aimed to expand our knowledge of the underlying mechanisms of orthostatic tolerance. First, cerebral perfusion was compared with reductions in orthostatic tolerance between normal thermic and heated conditions. The researchers' hypothesized that subjects with the greatest reduction in orthostatic tolerance will experience the largest drop in cerebral blood flow. Additionally, ANG II was measured in order to identify if during passive heating, the elevation in plasma ANG II is negatively correlated with heat-stress induced reductions in orthostatic tolerance. Lastly, orthostatic tolerance changes during the simulated hemorrhage between heat stress and normal thermic conditions will be compared to fitness level, measured by VO2 max. Results and Conclusion: Cerebral perfusion, as indexed by middle cerebral artery blood velocity, was reduced during heat stress compared with normothermia (P [less than] 0.001); however, the magnitude of reduction did not differ between groups (P = 0.51). In the initial stage of LBNP during heat stress (LBNP 20 mmHg), middle cerebral artery blood velocity and end-tidal PCO2 were lower; whereas, heart rate was higher in the large difference group compared with small difference group (P [less than] 0.05 for all). In opposition to the hypotheses, the large differences in tolerance to a simulated hemorrhage during normothermic and heat stress conditions are not solely related to the degree of heat stress-induced reduction in cerebral perfusion. Also, an individual's level of cardiorespiratory capacity (fitness) and/or the degree of heat stress-induced increase in plasma ANG II does not reliably predict the level of reduction in tolerance to a simulated hemorrhage challenge when heat stressed. / text