Academisch Proefschrift--Universiteit van Amsterdam, 2007. / Description based on print version record. Includes bibliographical references (p. 91-108).

Abstract Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease which is characterized by resting tremor, rigidity, bradykinesia and postural instability. Advanced PD is often complicated by falls, immobilisation and progressive deterioration of overall physical capability that may jointly contribute to a reduced quality of life and even to increased mortality. The purpose of this study was to identify risk factors for falls and mortality in PD, to assess the clinical correlates of balance and mobility, and to evaluate the association between orthostatic hypotension (OH), balance and mobility. From a total population of approximately 205 000 inhabitants, 125 patients with idiopathic PD were included in the study. Baseline medical data including occurrence of recent falls were collected, and patients were clinically tested for balance, mobility and orthostatic blood pressure reactions. Falls were thereafter prospectively recorded for two years using fall diaries and follow-up calls. Mortality was documented by reviewing the hospital charts four years after the baseline examination. In the cross-sectional part of the study, one-third of the patients reported recent falling. Disease duration and severity, recent falling and use of a walking aid were predictors of increased postural sway in PD. Advanced age and severity of the disease were related to impaired balance and mobility in PD patients. Severity of the disease and increased postural sway were independent risk factors for recent falling in PD, whereas measures of mobility were less important in this manner. Fifty-three percent of the patients had OH in the orthostatic test. Patients with OH had significantly increased postural sway in standing compared to patients without OH. On the contrary, OH was not associated with mobility and walking speed. In the present data, OH was not associated with the risk of falling in PD. Sixty-three percent of the study patients experienced falls and almost half of the subjects fell recurrently during the two-year follow-up. History of falling and disease severity indicated increased risk of recurrent falls in PD, while patients with slow walking speed had an increased risk of mortality. The results show that balance impairment and falls are common features in PD. Slow walking speed may be associated with increased mortality in PD.

One of the age-related changes associated with normal aging is the inability to maintain normal blood pressure homeostasis, a common clinical condition known as orthostatic intolerance. There are little data on the effects of strength training in healthy adults and orthostatic intolerance, and only one study on strength training and elderly adults diagnosed with orthostatic intolerance. Therefore, the purpose of the present study was to evaluate the effects of resistance training on the cardiovascular respones of elderly individuals during an orthostatic challenge. Thirteen subjects were assigned to either a resistance (RES; n=7; 66±5 yrs.) or a control (CON; n=6; 71±6 yrs.) group. During the 12-week treatment period, the RES trained 2x/wk, while the CON was asked not to change their normal lifestyles. The resistance training consisted of 3 sets of 8-12 repetitions using 12 machines at approximately 22% to 57% of 1RM. Before and after the training and control period, subjects were tested using a 70 degree head-up tilt. Tilt consisted of 30 minutes of supine rest while heart rate(HR) was recorded every minute and blood pressure (BP) was taken every 5 minutes. After the rest period, subjects were tilted to 70 degrees for 30 minutes unless subjects experienced presyncopal symptoms. During the tilt period, HR and BP were recorded every minute. After the tilt, subjects were placed in a supine position for 15 minutes of recovery, HR was taken every minute, and BP was taken every 5 minutes. A 2X2X8(test X group X time) Repeated Measures Analysis of Variance was used to analyze data. Significance was accepted at p ≤ 0.05. After the 12 weeks of training, the RES significantly increased upper (46±24 to 55±29kg) and lower (62±20 to 80±31kg) body strength while the CON showed no changes. Body composition measurements by DEXA showed lean mass to increase significantly (50.5±12.9 to 52.7±13.1kg) for the RES group, while the CON showed no changes. Of the 13 subjects only 9 subjects completed the pre and post tilt tests. Of the 9 completing both tilt periods, there were no significant differences between groups for any of the dependent measures of HR, systolic blood pressure, diastolic blood pressure and mean arterial pressure. In conclusion, this study demonstrated that a resistance training program was well tolerated and improved strength and lean mass in the RES. However, training did not help these individuals improve cardiovascular responses to an orthostatic challenge.

Maintenance of stable arterial blood pressure during orthostatic challenges is a major problem after spinal cord injury (SCI). Since early participation in rehabilitation is critically important in reducing long term morbidity, recovering the ability to regulate blood pressure during therapy is essential for individuals with SCI. The objective of our study was to investigate short term cardiovascular function of able-bodied (AB), paraplegic (PARA) and tetraplegic (TETRA) subjects in response to head up tilt (HUT) as an early indicator of autonomic damage that might forewarn of future orthostatic regulatory problems. We acquired cardiovascular variables from able-bodied (AB; n=11), paraplegic (PARA; n=5) and tetraplegic (TETRA; n=5) subjects in response to HUT. The SCI patients in both groups were in their first two months post injury. Data were recorded at rest and during 7 min each at 20??, 40??, 60?? and 80?? HUT. Techniques used to estimate regulatory capability and reflex activity included: Mean values and spectral power of heart rate (HR) and arterial blood pressure (BP), baroreflex sequence measurements and cross correlation between HR and systolic blood pressure (SBP). An index of baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), and the percentage occurrence of systolic blood pressure (BP) ramps and baroreflex sequences were calculated from baroreflex sequence measurements. The spectral power of HR and BP, the cross correlation of systolic BP and heart rate (HR) were examined in low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4 Hz) ranges. The BRS index was significantly (p andlt; 0.05) decreased from supine to 80o HUT in AB and TETRA. This index in PARA was the lowest at each tilt position in the three groups, and decreased with tilt. The percentage of heart beats involved in systolic BP ramps and in baroreflex sequences significantly (pandlt;0.05) rose from supine to 80o HUT in AB, was relatively unchanged in PARA and declined in TETRA. Both of these indexes were significantly (pandlt;0.05) lowerin the SCI than in the AB group at each tilt level. The BEI values were greatest in AB, and declined with tilt in all groups. Spinal cord injured patients had less power of BP and HR fluctuations than AB in both LF and HF regions. The LF spectral power of BP and HR increased with tilt in AB, remained unchanged in PARA and decreased in TETRA. The HF spectral power of HR decreased in all three groups. The peak HR / BP cross correlation in the LF region was greatest in AB, and significantly (pandlt;0.05) increased during HUT in AB, remained fairly constant in PARA, and declined in TETRA. The peak cross correlation in the HF region significantly (pandlt;0.05) decreased with tilt in all groups, and the SCI group had lower values than AB at each tilt level. We conclude that both PARA and TETRA had a smaller percentage of SBP ramps, BRS, and lower BEI than AB, likely indicating decreased stimulation of arterial baroreceptors, and less engagement of feedback control. The mixed sympathetic, parasympathetic innervations of paraplegics, or their elevated HR, may contribute to their significantly lower BRS. Our data indicate that the pathways utilized to evoke baroreflex regulation of HR are compromised by SCI and this loss may be a major contributor to the decrease in orthostatic tolerance following injury.

RESUMEN OBJETIVO: Determinar la prevalencia de Hipotensión ortostática (HO) en el adulto mayor que se hospitaliza por enfermedades médicas tanto a la admisión como al momento del alta. MÉTODO: 33 pacientes mayores de 60 años hospitalizados en los Servicios de Medicina entre los meses de Setiembre a Noviembre del 2004 participaron en el estudio. Se midió la Presión arterial a las 6:30am en posición supina y en bipedestación al 3er y 5to minuto. Considerando a la HO como la reducción de la PAS20mm. Hg. y/o PAD10mm Hg. al 3er y 5to minuto de pasar de la posición supina a la posición erguida. Además se aplicó un cuestionario para determinar los factores de riesgo y síntomas de la HO. RESULTADOS: Se encontró una prevalencia de HO de 36.4% en la población anciana estudiada. Se identificó una relación entre HO y mayor tiempo de estancia hospitalaria; Además se logró determinar que los medicamentos más usados por los pacientes con HO eran los diuréticos (66.7%) y los IECAS (44.4%); Los síntomas más frecuentes fueron los mareos (75%), caídas (58.3%), escotomas (50%). No se encontró relación entre la HO y otros factores de riesgo. CONCLUSIÓN: La prevalencia de HO encontrada es relativamente alta (36.4%) por lo que hay que tenerla en cuenta al momento de realizar el examen físico. La HO se encuentra asociada a un mayor tiempo hospitalario y a la ingesta de fármacos como diuréticos e IECAS. Se recomienda seguir investigando otras posibles asociaciones de la HO como por ejemplo mortalidad.

Orthostatic hypotension (OH) is a prevalent condition among individuals with spinal cord injury (SCI). After an injury, OH often reduces the benefit of neurorehabilitation and also prolongs periods of inactivity that lead to secondary complications. This study investigated whether the cardiovascular response to head-up tilting can be improved using functional electrical stimulation (FES) and rhythmic passive movements of the lower extremities. Participants with high thoracic and cervical SCI were recruited. While the participants were tilted head-up to 70 degrees, four conditions were applied in a random sequence: 1) no intervention, 2) rhythmic passive leg movements, 3) isometric FES, and 4) a combination of FES and passive leg movements. The measured cardiovascular parameters indicated that a combination of FES and passive leg movements induced the most desirable response to head-up tilting. The proposed intervention will enable more individuals with SCI to participate in beneficial neurorehabilitation that uses a novel tilt table.

Orthostatic hypotension (OH) is a prevalent condition among individuals with spinal cord injury (SCI). After an injury, OH often reduces the benefit of neurorehabilitation and also prolongs periods of inactivity that lead to secondary complications. This study investigated whether the cardiovascular response to head-up tilting can be improved using functional electrical stimulation (FES) and rhythmic passive movements of the lower extremities. Participants with high thoracic and cervical SCI were recruited. While the participants were tilted head-up to 70 degrees, four conditions were applied in a random sequence: 1) no intervention, 2) rhythmic passive leg movements, 3) isometric FES, and 4) a combination of FES and passive leg movements. The measured cardiovascular parameters indicated that a combination of FES and passive leg movements induced the most desirable response to head-up tilting. The proposed intervention will enable more individuals with SCI to participate in beneficial neurorehabilitation that uses a novel tilt table.

Despite years of research, the role that hypovolemia plays in orthostatic intolerance after head down bed rest (BR) and spaceflight remains unclear. Additionally, the efficacy of oral saline countermeasures, employed in an attempt to restore plasma volume (PV) after BR is questionable. Several previous studies have suggested that a new homeostatic set point is achieved in space or during BR, making attempts to restore PV temporary at best. We tested the hypotheses that one day of BR would induce a transient increase in PV followed by hypovolemia and new hormonal balance; that a salt tablet and water fluid loading (FL) countermeasure would be ineffective in restoring PV; and also that the FL would not attenuate the exaggerated hormonal responses to orthostatic stress that are expected after 28hr of BR. Plasma volume, serum sodium and osmolarity, and plasma ANP, AVP, renin, angiotensin II, aldosterone, and catecholamines were measured in nine male subjects undergoing 5 different protocols (28hr Bed Rest without Fluid Loading = 28NFL, 28hr Bed Rest with Fluid Loading = 28FL, 4hr Seated Control = 4NFLS, 4hr Seated Control with Fluid Loading = 4FLS, and 4hr Bed Rest = 4BR) in a randomized repeated measures design. The FL countermeasure was 15 ml/kg of body weight of water with 1g of NaCl per 125ml of water. Orthostatic testing by lower body negative pressure (LBNP) was performed before and after all protocols. In agreement with our first hypothesis, we observed transient reductions in renin, angiotensin II, and aldosterone, which after 25.5hr were restored to baseline, slightly augmented, and suppressed, respectively. Also after 25.5hr, PV was reduced in the 28hr BR protocols and was not restored in 28FL; however, the FL protocol increased PV during 4FLS. We additionally observed augmented renin and aldosterone responses, as well as generally elevated angiotensin II after 28NFL, but not after 28FL or any of the 4hr protocols. Furthermore, no changes in plasma norepinephrine responses to LBNP were documented from Pre-Post test in any protocol. Our results indicate that: 1) PV is reduced after short term BR and is not restored by an oral FL; 2) renin-angiotensin-aldosterone system (RAAS) responses to orthostatic stress are augmented after 28hr of BR and the amplified response can be abrogated by FL; and 3) plasma norepinephrine responses during orthostatic stress are not affected by BR or FL, suggesting that RAAS activity may be modulated by FL independently of sympathetic activity and PV during orthostasis after bed rest.

Despite years of research, the role that hypovolemia plays in orthostatic intolerance after head down bed rest (BR) and spaceflight remains unclear. Additionally, the efficacy of oral saline countermeasures, employed in an attempt to restore plasma volume (PV) after BR is questionable. Several previous studies have suggested that a new homeostatic set point is achieved in space or during BR, making attempts to restore PV temporary at best. We tested the hypotheses that one day of BR would induce a transient increase in PV followed by hypovolemia and new hormonal balance; that a salt tablet and water fluid loading (FL) countermeasure would be ineffective in restoring PV; and also that the FL would not attenuate the exaggerated hormonal responses to orthostatic stress that are expected after 28hr of BR. Plasma volume, serum sodium and osmolarity, and plasma ANP, AVP, renin, angiotensin II, aldosterone, and catecholamines were measured in nine male subjects undergoing 5 different protocols (28hr Bed Rest without Fluid Loading = 28NFL, 28hr Bed Rest with Fluid Loading = 28FL, 4hr Seated Control = 4NFLS, 4hr Seated Control with Fluid Loading = 4FLS, and 4hr Bed Rest = 4BR) in a randomized repeated measures design. The FL countermeasure was 15 ml/kg of body weight of water with 1g of NaCl per 125ml of water. Orthostatic testing by lower body negative pressure (LBNP) was performed before and after all protocols. In agreement with our first hypothesis, we observed transient reductions in renin, angiotensin II, and aldosterone, which after 25.5hr were restored to baseline, slightly augmented, and suppressed, respectively. Also after 25.5hr, PV was reduced in the 28hr BR protocols and was not restored in 28FL; however, the FL protocol increased PV during 4FLS. We additionally observed augmented renin and aldosterone responses, as well as generally elevated angiotensin II after 28NFL, but not after 28FL or any of the 4hr protocols. Furthermore, no changes in plasma norepinephrine responses to LBNP were documented from Pre-Post test in any protocol. Our results indicate that: 1) PV is reduced after short term BR and is not restored by an oral FL; 2) renin-angiotensin-aldosterone system (RAAS) responses to orthostatic stress are augmented after 28hr of BR and the amplified response can be abrogated by FL; and 3) plasma norepinephrine responses during orthostatic stress are not affected by BR or FL, suggesting that RAAS activity may be modulated by FL independently of sympathetic activity and PV during orthostasis after bed rest.

The potential role of lower limb blood pooling in reducing venous return to the heart during orthostasis and elevated venous pressure is investigated. This study compares lower limb capacitance, microvascular filtration, and peripheral resistance between a group of highly trained endurance athletes and a group of their sedentary peers. Seven endurance trained males were selected between the ages of 23-33 [(29.1 4.1 yr), mean SD]. The subjects weekly cycling mileage ranged from 80 to 150 miles per week with an average of 125 8.5 miles/week. Nine healthy, age-matched sedentary subjects (25.8 4.8 yr.) were selected for the control group, based upon their reporting they had not participated in repeated lower-body or cardiovascular exercise in the months prior to their study. Results show that both subject groups had similar calf venous capacitances, rates of capillary fluid filtration, and local flow shunting (vascular resistance change) in response to venous thigh occlusion and 70 head-up tilt (HUT). The only significant difference found between groups was the cyclist groups smaller rise in heart rate in response to HUT. The findings of this study suggest that cyclists are not predisposed to orthostatic intolerance due to any changes in lower limb function.