Deconditioning is a risk factor for cardiovascular disease. The physiology of vascular adaptation to deconditioning has not been elucidated. The purpose of the present study was to assess the effects of bed rest deconditioning on vascular dimension and function of leg conduit arteries. In addition, the effectiveness of resistive vibration exercise as a countermeasure for vascular deconditioning during bed rest was evaluated. Sixteen healthy men were randomly assigned to bed rest (BR-Ctrl) or to bed rest with resistive vibration exercise (BR-RVE). Before and after 25 and 52 days of strict horizontal bed rest, arterial diameter, blood flow, flow-mediated dilatation (FMD), and nitroglycerin-mediated dilatation were measured by echo Doppler ultrasound. In the BR-Ctrl group, the diameter of the common femoral artery decreased by 13 +/- 3% after 25 and 17 +/- 1% after 52 days of bed rest (P < 0.001). In the BR-RVE group this decrease in diameter was significantly attenuated (5 +/- 2% after 25 days and 6 +/- 2% after 52 days, P < 0.01 vs. BR-Ctrl). Baseline blood flow did not change after bed rest in either group. After 52 days of bed rest, FMD and nitroglycerin-mediated dilatation of the superficial femoral artery were increased in both groups, possibly by increased nitric oxide sensitivity. In conclusion, bed rest deconditioning is accompanied by a reduction in the diameter of the conduit arteries and by an increased reactivity to nitric oxide. Resistive vibration exercise effectively attenuates the diameter decrease of leg conduit arteries after bed rest.

Flow-mediated dilatation (FMD) of the brachial and radial arteries is an important research tool for assessment of endothelial function in vivo, and is nitric oxide (NO) dependent. The leg skeletal muscle vascular bed is an important territory for studies in exercise physiology. However, the role of endothelial NO in the FMD response of lower limb arteries has never been investigated. The purpose of this study was to examine the contribution of NO to FMD in the superficial femoral artery in healthy subjects. Since physical inactivity may affect endothelial function, and therefore NO availability, spinal cord-injured (SCI) individuals were included as a model of extreme deconditioning. In eight healthy men (34 ± 13 years) and six SCI individuals (37 ± 10 years), the 5 min FMD response in the superficial femoral artery was assessed by echo-Doppler, both during infusion of saline and during infusion of the NO synthase blocker N G -monomethyl-L-arginine (L-NMMA). In a subset of the controls (n = 6), the 10 min FMD response was also examined using the same procedure. The 5 min FMD response in controls (4.2 ± 0.3%) was significantly diminished during L-NMMA infusion (1.0 ± 0.2%, P < 0.001). In SCI, L-NMMA also significantly decreased the FMD response (from 8.2 ± 0.4% during saline to 2.4 ± 0.5% during L-NMMA infusion). The hyperaemic flow response during the first 45 s after cuff deflation was lower in both groups during infusion of L-NMMA, but the effect of L-NMMA on FMD persisted in both groups after correction for the shear stress stimulus. The 10 min FMD was not affected by L-NMMA (saline: 5.4 ± 1.6%, L-NMMA: 5.6 ± 1.5%). Superficial femoral artery FMD in response to distal arterial occlusion for a period of 5 min is predominantly mediated by NO in healthy men and in the extremely deconditioned legs of SCI individuals.

Physical inactivity or deconditioning is an independent risk factor for atherosclerosis and cardiovascular disease. In contrast to exercise, the vascular changes that occur as a result of deconditioning have not been characterized. We used 4 wk of unilateral lower limb suspension (ULLS) to study arterial and venous adaptations to deconditioning. In contrast to previous studies, this model is not confounded by denervation or microgravity. Seven healthy subjects participated in the study. Arterial and venous characteristics of the legs were assessed by echo Doppler ultrasound and venous occlusion plethysmography. The diameter of the common and superficial femoral artery decreased by 12% after 4 wk of ULLS. Baseline calf blood flow, as measured by plethysmography, decreased from 2.1 +/- 0.2 to 1.6 +/- 0.2 ml.min(-1).dl tissue(-1). Both arterial diameter and calf blood flow returned to baseline values after 4 wk of recovery. There was no indication of a decrease in flow-mediated dilation of the superficial femoral artery after ULLS deconditioning. This means that functional adaptations to inactivity are not simply the inverse of adaptations to exercise. The venous pressure-volume curve is shifted downward after ULLS, without any effect on compliance. In conclusion, deconditioning by 4 wk of ULLS causes significant changes in both the arterial and the venous system.

Objective: To assess the time course of adaptations in leg vascular dimension and function within the first 6 weeks after a spinal cord injury (SCI).Design: Longitudinal study design. Setting: University medical center and rehabilitation clinic. Participants: Six men were studied serially at 1, 2, 3, 4, and 6 weeks after SCI.Interventions: Not applicable. Main Outcome Measures: Diameter, blood flow, and shear rate levels of the common femoral artery (CFA), superficial femoral artery (SFA), brachial artery, and carotid artery were measured with echo Doppler ultrasound (diameter, blood flow, shear rate). Endothelial function in the SFA was measured with flow-mediated dilation (FMD). In addition, leg volume and blood pressure measurements were performed.Results: Femoral artery diameter (CFA, 25%; SFA, 16%; PϽ.01) and leg volume (22%, PϽ.01) decreased simultaneously, and these reductions were largely accomplished within 3 weeks postinjury. Significant increases were observed for basal shear rate levels (64% increase at week 3; 117% increase at week 6; PϽ.01), absolute FMD responses (8% increase at week 3, 23% increase at week 6; PϽ.05) and relative FMD responses (26% increase at week 3, 44% increase at week 6; PϽ.001).Conclusions: Our findings show a rapid onset of adaptations in arterial dimension and function to extreme inactivity in humans. Vascular adaptations include extensive reductions in femoral diameter and leg volume, as well as increased basal shear rate levels and FMD responses, which all appear to be largely accomplished within 3 weeks after an SCI.

Venous occlusion plethysmography is commonly used as a tool to assess BF (blood flow) and VR (vascular resistance) at baseline and during PORH (post-occlusive reactive hyperaemia). However, little is known about the reproducibility of this method. The purpose of the present study was to investigate short- (hours) and medium (week)-term reproducibility of forearm, calf and thigh BF and VR at baseline and during PORH. Reproducibility was assessed by the CV (coefficient of variation). In eight subjects, baseline BF and VR of the forearm, calf and thigh were measured using venous occlusion plethysmography (50 mmHg). PORH and minimal VR were measured after 13 min of arterial occlusion (220 mmHg). Reproducibility of baseline forearm and calf BF was acceptable and in agreement with previous studies (CV, 12.9-21.2%). Short- and medium-term reproducibility of thigh BF was good (CV, 5.9% and 8.7% respectively). Baseline VR showed acceptable-to-good reproducibility for forearm, calf and thigh (8.3-22.5%). Forearm PORH showed a CV of 6.1% (short term) and 8.6% (medium term); this was 6.1% (short term) and 6.4% (medium term) for the calf and 6.4% (short term) and 8.0% (medium term) for the thigh. Minimal VR showed good-to-acceptable reproducibility (CV, 6.1-11.7%). In conclusion, forearm, calf and thigh BF and PORH measured by plethysmography have an acceptable-to-good short- and medium-term reproducibility. Short- and medium-term reproducibility of forearm and calf baseline BF are acceptable and thigh baseline BF has a good short- and medium-term reproducibility. Therefore plethysmography is a suitable low-cost tool to assess thigh baseline BF and PORH.

Classical venous occlusion plethysmography (VOP) of the leg, often used to assess venous compliance, measures properties of the whole calf, including volume changes at the arterial side and the interstitial fluid accumulation that occurs as a result of the enhanced capillary pressure during venous occlusion. We present an ultrasound technique to measure the compliance of one major conduit vein in the leg. Ultrasound measurements of the popliteal vein were compared with classical VOP measurements, which were performed simultaneously in one subject. Six healthy individuals were measured on three occasions to assess short- and long-term reproducibility of the measurements. Six motor complete spinal cord-injured (SCI) individuals were included to compare venous compliance in subjects with known pathological changes of the venous system with controls. The ultrasound and VOP measurements of venous compliance correlated significantly (r(2) = 0.39, P = 0.001). Ultrasound provides reproducible measurements with short- and long-term coefficients of variation ranging from 10 to 15% for popliteal vein compliance and from 2 to 9% for absolute diameters at the different venous pressure steps. In addition, by using ultrasound, we were able to detect an 80% reduction in the compliance of the popliteal vein in SCI individuals compared with controls (P < 0.01). In conclusion, ultrasound is a suitable and reproducible method to measure conduit vein compliance and provides the possibility to specifically assess compliance of one vein instead of the whole calf.

Deconditioning is a risk factor for cardiovascular disease. Exercise reduces this risk, possibly by improving the vascular endothelial nitric oxide (NO) pathway. The effect of deconditioning on the NO pathway is largely unknown. This study was designed to assess baseline NO availability in the leg vascular bed after extreme, long-term deconditioning (spinal cord-injured individuals, SCI) as well as after moderate, short-term deconditioning (4 weeks of unilateral lower limb suspension, ULLS). For this purpose, seven SCI were compared with seven matched controls. Additionally, seven healthy subjects were studied pre-and post-ULLS. Leg blood flow was measured by venous occlusion plethysmography at baseline and during infusion of 5 incremental dosages of N G -monomethyl-L-arginine (L-NMMA) into the femoral artery. Sodium nitroprusside (SNP) was infused to test vascular responsiveness to NO. Baseline leg vascular resistance tended to be higher in SCI compared with controls (37 ± 4 versus 31 ± 2 arbitrary units (AU), P = 0.06). Deconditioning altered neither the vasoconstrictor response to L-NMMA (increase in resistance in SCI versus controls: 102 ± 33% versus 69 ± 9%; pre-versus post-ULLS: 95 ± 18% versus 119 ± 15%), nor the vascular responsiveness to NO. In conclusion, two human in vivo models of deconditioning show a preserved baseline NO availability in the leg skeletal muscle vascular bed.

We demonstrate that extensive arterial vascular adaptations occur within 3-8 wk of inactivity in humans. We put forth the hypothesis that the diameter decrease represents an adaptation to a lack of variation in peak shear stress. Furthermore, an enhanced flow-mediated dilation in deconditioned arteries implies that functional vascular adaptations to inactivity are not simply the inverse of adaptations to exercise.