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AIM: To identify independent predictors of contrast medium-induced acute kidney injury (CI-AKI) after enhanced multidetector-row computed tomography (MDCT) prior to transcatheter aortic valve implantation (TAVI) in high-risk patients. MATERIALS AND METHODS: The present single-centre study analysed retrospectively 361 patients who were assessed using MDCT prior to TAVI. CI-AKI was defined as an increase in serum creatinine (SCr) of ≥ 25% or ≥ 0.5 mg/dl in at least one sample over baseline (24 h before MDCT) and at 24, 48, and 72 h after MDCT. RESULTS: A total of 38 patients (10.5%) experienced CI-AKI. As compared to patients without CI-AKI, they presented more frequently with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2), (81.6% versus 64.4%, p = 0.045) and tended to receive higher volumes of iodinated contrast media (ICM; 55.3% versus 39%, p = 0.057). There was a significant interaction between baseline eGFR and the amount of intravenous ICM administered (pfor interaction = <0.001) identifying the amount of ICM >90 ml as independent predictive factor of CI-AKI only in patients with baseline eGFR <60 ml/min/1.73m(2) (OR 2.615; 95% CI: 1.21-5.64). CONCLUSION: One in ten elderly patients with aortic stenosis undergoing MDCT to plan a TAVI procedure experienced CI-AKI after intravenous ICM injection. Intravenous administration of <90 ml of ICM reduces this risk in patients with or without pre-existing impaired renal function. However, in the majority of patients renal function recovers before the TAVI procedure.

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Bed rest, both with and without head-down tilt, has been extensively used as an earth-bound analog to study physiologic effects mimicking those occurring in weightlessness during spaceflight. We have been able to show in six subjects that 4 weeks of head-down tilt bed rest induces a significant decrease in interleukin-2 secretion by PHA-stimulated T lymphocytes. Another study, lasting 113 days, with two subjects showed a decreased interleukin-2 receptor expression in PHA-stimulated peripheral blood mononuclear cells but a decreased interleukin-2 production in one subject only. Under the same conditions, interleukin-1 production was largely increased in both subjects. Several other immune parameters were also analyzed. Increased interleukin-1 production could contribute to bone mineral loss encountered during bed rest and decreased interleukin-2 secretion could play a role in the appearance of infectious diseases often observed during bed red.

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This study examined the heart rate response to lower body negative pressure (LBNP) during 17 weeks of horizontal bed rest to estimate the development and duration of orthostatic instability elicited by this model for space flight. Based on data from Skylab, the authors hypothesized that orthostatic (LBNP) instability would appear during the first 3 to 4 weeks, and would then remain constant for the duration of bed rest. Heart rates of four healthy adult male subjects were monitored at rest and during LBNP for 1 week of ambulatory control, 17 weeks of horizontal bed rest, and 5 weeks of recovery. The LBNP protocol consisted of 10 minutes of control (atmospheric pressure) and 5 minutes each at 5, 10, 20, 30, 40, and 50 mm Hg decompression, followed by a 10-minute recovery period; this protocol was repeated weekly to document the progressive changes in heart rate response to LBNP. Lower body negative pressure was terminated early if symptoms compatible with the onset of syncope occurred. Throughout the study, heart rate was unchanged at 5, 10, and 20 mm Hg, but it increased at 30, 40, and 50 mm Hg LBNP. During the pre-bed rest period, peak heart rate was 97 +/- 10 beats/min (mean +/- SE), occurring at 50 mm Hg for all four subjects. After 3 days of bed rest, all monitored heart rate responses, including values after release of LBNP, were only slightly elevated (NS) above pre-bed rest level. Peak heart rate was 118 +/- 21 beats/min at 50 mm Hg decompression (NS; N = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

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STUDY DESIGN: We measured the cross-sectional area of the intervertebral discs of normal volunteers after an overnight rest; before, during, and after 5 or 17 weeks of bed rest; and before and after 8 days of weightlessness. OBJECTIVES: This study sought to determine the degree of expansion of the lumbar discs resulting from bed rest and space flight. SUMMARY OF BACKGROUND DATA: Weightlessness and bed rest, an analog for weightlessness, reduce the mechanical loading on the musculoskeletal system. When unloaded, intervertebral discs will expand, increasing the nutritional diffusion distance and altering the mechanical properties of the spine. METHODS: Magnetic resonance imaging was used to measure the cross-sectional area and transverse relaxation time (T2) of the intervertebral discs. RESULTS: Overnight or longer bed rest causes expansion of the disc area, which reaches an equilibrium value of about 22% (range 10-40%) above baseline within 4 days. Increases in disc area were associated with modest increases in disc T2. During bed rest, disc height increased approximately 1 mm, about one-half of previous estimates based on body height measurements. After 5 weeks of bed rest, disc area returned to baseline within a few days of ambulation, whereas after 17 weeks, disc area remained above baseline 6 weeks after reambulation. After 8 days of weightlessness, T2, disc area, and lumbar length were not significantly different from baseline values 24 hours after landing. CONCLUSIONS: Significant adaptive changes in the intervertebral discs can be expected during weightlessness. These changes, which are rapidly reversible after short-duration flights, may be an important factor during and after long-duration missions.

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The effects of long-term bed rest on zinc and copper balances were measured in seven healthy men. Volunteers aged 22-54 y (mean +/- SD, 34 +/- 12 y), 168-185 cm in height (173 +/- 5 cm), and 64-86 kg in weight (74 +/- 9 kg) remained on a metabolic ward for 29 wk. Subjects were ambulatory during weeks 1-5, remained in continuous bed rest for weeks 6-22, and were reambulated during weeks 23-29. Copper and zinc were measured in weekly urine and fecal composites. Dietary intakes provided (mean +/- SD) 19.2 +/- 1.2 mumol Cu (1.22 +/- 0.08 mg), 211 +/- 11 mumol Zn (13.81 +/- 0.72 mg), 25.2 +/- 1.2 mmol Ca (1011 +/- 46 mg), 1086 +/- 46 mmol N (15.21 +/- 0.65 g), and 48.1 +/- 1.4 mmol K (1489 +/- 44 mg)/d. Bed rest increased fecal zinc excretion and decreased zinc balance, whereas copper balance was unchanged. Reambulation decreased fecal zinc excretion and increased both zinc and copper balances. These results suggest that during long-term bed rest or space flight, individuals will lose total body zinc and will retain more zinc and copper when they reambulate.

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This paper emphasizes the devastating effects of displacement of calcium during space flight, due to increased bone turnover.

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This work reports on the muscle loss and recovery after 17 wk of continuous bed rest and 8 wk of reambulation in eight normal male volunteers. Muscle changes were assessed by urinary levels of 3-methylhistidine (3-MeH), nitrogen balance, dual-photon absorptiometry (DPA), magnetic resonance imaging (MRI), and isokinetic muscle performance. The total body lean tissue loss during bed rest calculated from nitrogen balance was 3.9 +/- 2.1 (SD) kg (P < 0.05). Although the total loss is minimal, DPA scans showed that nearly all of the lean tissue loss occurred in the lower limbs. Similarly, MRI muscle volume measurements showed greater percent loss in the limbs relative to the back muscles. MRI, DPA, and nitrogen balance suggest that muscle atrophy continued throughout bed rest with rapid recovery after reambulation. Isokinetic muscle strength decreased significantly (P < 0.05) in the thigh and calf with no loss in the arms and with rapid recovery during reambulation. We conclude that there is great variability in the degree and location of muscle loss in bed rest and that the lower limb muscles are primarily affected.

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A technique of quantitative digital roentgenography (QDR) being a current modification of dual photon absorptiometry (DPA) was used to measure bone mineral density (BMD) in the crewmembers of the 6-9th expeditions onboard Mir orbital station after space missions of 132 to 176 days in duration. Total mineral losses were, on average, 0.4% of a preflight level, and in the most test subjects the postflight BMD of the skull, ribs and arms increased and that of lumbar vertebrae, pelvis and legs decreased. The most marked local postflight mineral losses occurred in the proximal femur bone (the femoral neck and the greater trochanter--up to 14%). The observed changes did not depend on flight duration. These findings are being compared to the results of similar studies conducted during the 120-day (NASA) and 370-day (IBMP) hypokinesia experiments. The possibility of existing the general mechanism of modifying mineral status of the skeleton due to different situation related deficiency of musculoskeletal load.

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The purpose of this work was to determine the rate and extent of bone loss and recovery from long-term disuse and in particular from disuse after exposure to weightlessness. For this purpose, bed rest is used to simulate the reduced stress and strain on the skeleton. This study reports on the bone loss and recovery after 17 weeks of continuous bed rest and 6 months of reambulation in six normal male volunteers. Bone regions measured were the lumbar spine, hip, tibia, forearm, calcaneus, total body, and segmental regions from the total-body scan. The total body, lumbar spine, femoral neck, trochanter, tibia, and calcaneus demonstrated significant loss, p less than 0.05. Expressed as the percentage change from baseline, these were 1.4, 3.9, 3.6, 4.6, 2.2, and 10.4, respectively. Although several areas showed positive slopes during reambulation, only the calcaneus was significant (p less than 0.05), with nearly 100% recovery. Segmental analysis of the total-body scans showed significant loss (p less than 0.05) in the lumbar spine, total spine, pelvis, trunk, and legs. During reambulation, the majority of the regions demonstrated positive slopes, although only the pelvis and trunk were significant (p less than 0.05). Potential redistribution of bone mineral was observed: during bed rest the bone mineral increased in the skull of all subjects. The change in total BMD and calcium from calcium balance were significantly (p less than 0.05) correlated, R = 0.88.

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Inactivity causes profound changes. We determined the nature of the body composition changes due to inactivity, and sought to determine if these changes are secondary to changes in energy absorption. Volunteers were 15 healthy males who lived on a metabolic research ward under close staff supervision for 11 weeks. Subjects were ambulatory during the first 6 weeks and remained in continuous bed rest for the last 5 weeks of the study. Six male volunteers (age 24-61 years, height 175.7 +/- 4.2 cm) were selected for body composition measurements. Nine different male volunteers (age 21-50 years, height 177.7 +/- 5.0 cm) were selected for energy absorption measurements. The volunteers were fed weighed conventional foods on a constant 7-d rotation menu. The average daily caloric content was 2,592 kcal. Comparing the 5 weeks of continuous bed rest with the previous 6 weeks of ambulation we observed: no change in energy absorption or total body weight during bed rest, but a significant decrease in lean body mass and a significant increase in total body fat (p less than 0.05).

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A group of 68 premenopausal women participated in a controlled 12 month exercise program. Two groups were matched according to age, body size (body mass index), and typical activity level. Data collection included bone mineral density (BMD) of the lumbar spine with dual-photon absorptiometry and of the os calcis with single-photon absorptiometry, lean body mass, urinary calcium/creatinine, and urinary gamma-carboxyglutamic acid (Gla). Subjects were given a daily 500 mg supplement of elemental calcium. There was no significant difference between groups in terms of diet, in urinary calcium/creatinine or Gla, or in lean body mass. The weight lifting group had a nonsignificant increase in mean lumbar BMD of 0.81% and the control group exhibited a nonsignificant decrease of 0.5%. However, a paired t-test revealed a significant change in the means in either group or as matched pairs. The relatively small change seen as a result of this modified Nautilus exercise program may prevent moderate weight lifting from being a practical answer for osteoporosis, even in a highly motivated population.

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Newer bone densitometers using dual-photon absorptiometry (DPA) or dual energy x-ray absorptiometry (DEXA) are capable of measuring the total-body bone mineral; regional analysis of these scans would have significant utility if adequate precision were possible. This study investigated short term precision by weekly scanning (three to five times) normal subjects (total 48 scans) and long term precision by scanning a whole-body phantom 30 times over 15 mo. For the 30 phantom scans, a coefficient of variation (CV) of bone mineral content (BMC) and bone mineral density (BMD) was calculated for each region. Nonrandom changes were analyzed by plotting the phantom data with time and testing the slope of the fitted line for significance. Similarly for the subjects, a CV for each region and the mean value for all subjects was obtained. From this study we conclude (a) BMD is more precise than BMC, (b) long-term precision was poorer than short term, (c) long-term regional BMD precision (%) was: head, 3.2; arms, 2.8; legs, 1.6; ribs, 2.6; pelvis, 3.8; thoracic spine, 3.8; lumbar spine, 7.1; total spine, 2.4; trunk, 2.2; total body, 1.2.

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The purpose of this study was to assess the effect of bed rest on appendicular muscle torque. Fifteen healthy male volunteers between the ages of 21 and 54 participated in the study. The subjects were put on five weeks of strict horizontal bed rest. They were allowed to sit up for bowel movements only; however, no lower extremity weight-bearing was allowed. During bed rest, the subjects were required to ingest a fixed nutritionally adequate diet. Data for muscle torque were obtained using a Cybex II dynamometer, Upper Body Exercise Table (UBXT), and a data analysis computer (HUMAC). The subjects were tested on Cybex at the speed of 60 degrees/sec during the week before starting bed rest and the day after starting reambulation. The muscle groups tested were soleus, gastrocnemius-soleus, dorsiflexors, knee flexors, knee extensors, elbow flexors, and elbow extensors. The torque in all groups but elbow extensors was reduced by 24%, 26%, 8%, 8%, 19%, and 7%, respectively. Student's t-test for paired means demonstrated significant loss of torque in all muscle groups except elbow extensors (p less than 0.05). The results of this study suggest that a strengthening exercise program should be administered to these patients while they are on bed rest, and that the earliest possible attempt should be made to ambulate patients after prolonged bed rest to minimize the loss of muscle torque.

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Magnetic resonance imaging of the spine was performed in six healthy male volunteers before and after 5 weeks of continuous bed rest. Imaging studies consisted of a single 1-cm sagittal section obtained with a spin-echo technique through the center of the spinal column. The T2s of the lumbar vertebral body and nucleus pulposus and the area of the latter were measured. In both vertebrae and disks, there was a significant decrease in T2 after bed rest. The nucleus pulposus also decreased in size with bed rest. The decrease in relaxation time of the lumbar vertebrae could be explained by the replacement of hematopoietic marrow by fatty marrow, a known consequence of paralytic immobilization. The decreases in size and T2 of the disks probably represent loss of water. The significance of these changes to the mechanical integrity of these structures after immobilization or space flight is not known but will depend in part on whether changes are progressive with increasing length of immobilization and on the rate and extent that they are reversed after reambulation. These results indicate that relaxation times can be altered by simple disuse, which often accompanies the underlying disease.

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The effects of bed rest and fluoride supplementation on zinc, copper, and nitrogen balances and Zn and Cu serum levels were measured in 15 healthy males. Subjects aged 19-54 y remained on a metabolic research ward for 10 wk. During weeks 1-5, subjects were ambulatory. During wks 6-10 they remained in continuous bed rest. During weeks 3-10 nine subjects received 10 or 20 mg F/d as sodium fluoride. Daily urine and weekly fecal composites were made and biweekly fasting blood samples were taken. Dietary intakes were 1.40 +/- 0.17 mg Cu/d (22.0 +/- 2.7 mumol Cu/d), 10.82 +/- 0.49 mg Zn/d (165.6 +/- 7.6 mumol Zn/d), and 14.27 +/- 0.23 g N/d (1019 +/- 16 mmol N/d). Bed rest increased urinary Zn and N excretions and fecal Zn excretions and decreased Zn balance (p less than 0.05) whereas Cu balance was unchanged. During bed rest, F supplementation increased Zn and N balances compared with untreated control subjects (p less than 0.05). These results are compatible with bone and muscle atrophy during bed rest and increased bone formation with F supplementation.

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Maintenance of a skeleton capable of resisting the stresses of everyday life is dependent on the mechanical forces applied to the skeleton during normal activity in a 1-G environment. When the effects of 1-G on the longitudinal skeleton are removed, as with space travel or inactivity, bone and bone mineral are lost because bone resorption is greater than bone formation. Ninety healthy young men were studied during 5-36 weeks of continuous bed rest. During inactivity, urinary calcium increases rapidly and by the sixth week of bed rest, output has risen by 100 mg/day, plateaus for several weeks, and then decreases but remains above ambulatory baseline thereafter. This occurred even though they received vitamin D supplements throughout the study. Calcium balance becomes negative after 2 weeks and by the end of the first month, 200 mg/day is lost. The loss continues at this rate for at least 36 weeks. Calcaneal mineral loses 5% of its mass each month. Attempts to prevent disuse osteoporosis with both mechanical and biochemical means, including exercise, skeletal compression, increased hydrostatic pressure to the lower body, supplemental calcium and/or phosphorus, calcitonin, or etidronate were not successful.

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Healthy men with a daily intake of 0.37 mg fluoride were given dichloromethylene diphosphonate (Cl2MDP) or a placebo during a period of ambulation followed by bed rest. In both groups, serum ionic fluoride was unchanged, and fluoride balances were negative, but Cl2MDP significantly reduced loss of fluoride in the treated groups.

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In a program of studies of disuse osteoporosis, fluoride balances were determined in healthy men during ambulation and then during bed rest for 6 to 17 wk. Control subjects ingested basal diets containing 0.4 mg fluoride per day, whereas experimental subjects received 10-mg fluoride supplements in divided doses with meals. Fluoride and calcium were measured in diets, urine, and feces. Serum analyses included calcium and ionic fluoride. Fluoride balances during both phases were uniformly negative in control subjects (mean -0.46 mg/day) but uniformly positive in supplement subjects (mean +2.58 mg/day). Calcium balances were markedly negative during bed rest in both groups. Serum fluoride concentrations increased proportionally to fluoride intake, averaging 0.016 ppm in the controls and 0.045 ppm in the supplement subjects. The supplement of 10 mg fluoride daily did not protect against bed rest-induced calcium loss, or cause any clinical or laboratory abnormality in any subject.

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Fluoride balances were determined in healthy adult males under metabolic ward conditions. This is the first fluoride study to use the diffusion method in exploring the balances of subjects ingesting basal (i.e., everyday) diets with deionized water for cooking and drinking. Certain groups were given daily supplements of 5 or 10 mg. fluoride as sodium fluoride in divided doses with meals. Fluoride was measured in the diets, sodium fluoride tablets, urine, feces, and serum. Approximately 90% of the fluoride excreted was found in the urine and the remainder in the feces in all groups. In the control subjects, fluoride balances were uniformly negative (mean of -0.40 mg/day); in contrast, balances were uniformly positive (mean of +1.38 and +2.88 mg/day, respectively) in subjects receiving 5 or 10 mg F supplements daily. Serum ionic fluoride concentration increased proportionally to fluoride intake and averaged 0.016, 0.029, and 0.040 ppm in the control, 5-mg and 10-mg groups, respectively. These fluoride supplements did not cause any clinical or laboratory abnormality in any subjects.

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