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PubMed1996

Fundamental relations between short-term RR interval and arterial pressure oscillations in humans.

BACKGROUND: One of the principal explanations for respiratory sinus arrhythmia is that it reflects arterial baroreflex buffering of respiration-induced arterial pressure fluctuations. If this explanation is correct, then elimination of RR interval fluctuations should increase respiratory arterial pressure fluctuations. METHODS AND RESULTS: We measured RR interval and arterial pressure fluctuations during normal sinus rhythm and fixed-rate atrial pacing at 17.2+/-1.8 (SEM) beats per minute greater than the sinus rate in 16 healthy men and 4 healthy women, 20 to 34 years of age. Measurements were made during controlled-frequency breathing (15 breaths per minute or 0.25 Hz) with subjects in the supine and 40 degree head-up tilt positions. We characterized RR interval and arterial pressure variabilities in low-frequency (0.05 to 0.15 Hz) and respiratory-frequency (0.20 to 0.30 Hz) ranges with fast Fourier transform power spectra and used cross-spectral analysis to determine the phase relation between the two signals. As expected, cardiac pacing eliminated beat-to-beat RR interval variability. Against expectations, however, cardiac pacing in the supine position significantly reduced arterial pressure oscillations in the respiratory frequency (systolic, 6.8+/-1.8 to 2.9 +/-0.6 mm Hg2/Hz, P=.017). In contrast, cardiac pacing in the 40 degree tilt position increased arterial pressure variability (systolic, 8.0+/-1.8 to 10.8 +/-2.6, P=.027). Cross-spectral analysis showed that 40 degree tilt shifted the phase relation between systolic pressure and RR interval at the respiratory frequency from positive to negative (9 +/-7 degrees versus -17+/-11 degrees, P=.04); that is, in the supine position, RR interval changes appeared to lead arterial pressure changes, and in the upright position, RR interval changes appeared to follow arterial pressure changes. CONCLUSIONS: These results demonstrate that respiratory sinus arrhythmia can actually contribute to respiratory arterial pressure fluctuations. Therefore, respiratory sinus arrhythmia does not represent simple baroreflex buffering of arterial pressure.

Adult↗
PubMed1996

Computerized mappings of the cerebral cortex: a multiresolution flattening method and a surface-based coordinate system.

We present a new method for generating two-dimensional maps of the cerebral cortex. Our computerized, two-stage flattening method takes as its input any well-defined representation of a surface within the three-dimensional cortex. The first stage rapidly converts this surface to a topologically correct two-dimensional map, without regard for the amount of distortion introduced. The second stage reduces distortions using a multiresolution strategy that makes gross shape changes on a coarsely sampled map and further shape refinements on progressively finer resolution maps. We demonstrate the utility of this approach by creating flat maps of the entire cerebral cortex in the macaque monkey and by displaying various types of experimental data on such maps. We also introduce a surface-based coordinate system that has advantages over conventional stereotaxic coordinates and is relevant to studies of cortical organization in humans as well as non-human primates. Together, these methods provide an improved basis for quantitative studies of individual variability in cortical organization.

Animals↗
PubMedDate not supplied

Oral branched-chain amino acids decrease whole-body proteolysis.

BACKGROUND: This study reports the effects of ingesting branched-chain amino acids (leucine, valine, and isoleucine) on protein metabolism in four men. METHODS: To calculate leg protein synthesis and breakdown, we used a new model that utilized the infusion of L-[ring-13C6]phenylalanine and the sampling of the leg arterial-venous difference and muscle biopsies. In addition, protein-bound enrichments provided for the direct calculation of muscle fractional synthetic rate. Four control subjects ingested an equivalent amount of essential amino acids (threonine, methionine, and histidine) to discern the effects of branched-chain amino acid nitrogen vs the effects of essential amino acid nitrogen. Each drink also included 50 g of carbohydrate. RESULTS: Consumption of the branched-chain and the essential amino acid solutions produced significant threefold and fourfold elevations in their respective arterial concentrations. Protein synthesis and breakdown were unaffected by branched-chain amino acids, but they increased by 43% (p < .05) and 36% (p < .03), respectively, in the group consuming the essential amino acids. However, net leg balance of phenylalanine was unchanged by either drink. Direct measurement of protein synthesis by tracer incorporation into muscle protein (fractional synthetic rate) revealed no changes within or between drinks. Whole-body phenylalanine flux was significantly suppressed by each solution but to a greater extent by the branched-chain amino acids (15% and 20%, respectively) (p < .001). CONCLUSIONS: These results suggest that branched-chain amino acid ingestion suppresses whole-body proteolysis in tissues other than skeletal muscle in normal men.

Adult↗
PubMedDate not supplied

The effect of nonablative laser energy on joint capsular properties. An in vitro histologic and biochemical study using a rabbit model.

The purpose of this study was to evaluate the effect of laser energy at nonablative levels on joint capsular histologic and biochemical properties in an in vitro rabbit model. The medial and lateral portions of the femoropatellar joint capsule from both stifles of 12 mature New Zealand White rabbits were used. Specimens were divided into three treatment groups (5 watts, 10 watts, and 15 watt) and one control group using a randomized block design. Specimens were placed in a 37 degrees bath of lactated Ringer's solution and laser energy was applied using a holmium:yttrium-aluminum-garnet laser in four transverse passes across the tissue at a velocity of 2 mm/sec with the handpiece set 1.5 mm from the synovial surface. Histologic analysis revealed thermal alteration of collagen (fusion) and fibroblasts (pyknosis) at all energy densities, with higher laser energy causing significantly greater morphologic changes over a larger area (P < 0.05). Application of laser energy did not significantly alter the biochemical parameters evaluated, including type I collagen content and nonreducible crosslinks (P > 0.05). This study demonstrated that nonablative laser energy caused significant thermal damage to the joint capsular tissue in an energy-dependent fashion, but type I collagen content and nonreducible crosslinks (P > 0.05). This study demonstrated that nonablative laser energy caused significant thermal damage to the joint capsular tissue in an energy-dependent fashion, but type I Collagen content and nonreducible corsslinks were not significantly altered.

Aluminum Silicates↗
PubMed1994

Phase-amplitude resetting of the human circadian pacemaker via bright light: a further analysis.

We present here an analysis of strong, weak, and critical bright-light resetting trials in humans, and report not only phase but also amplitude data for the first time. For this analysis, an appropriate iterative smoothing procedure for phase transition curves is introduced, in which the data are sequenced so as to minimize the perpendicular distance from the data to the smoothed fit. From these smoothed data, we create polar phase-amplitude resetting maps (PARMs) in order to fully illustrate the effects of the resetting stimuli on both circadian amplitude and phase, and thereby to determine whether these resetting results can be described by a phase-only model or whether a phase-amplitude model is required. Our results indicate that a single 5-hr episode of bright light induces weak type 1 resetting of the human circadian pacemaker. Two cycles of exposure to the same stimulus on consecutive days induce critical resetting, in which significant amplitude reduction may be observed. A three-cycle stimulus induces strong type 0 resetting with different effects on circadian amplitude, depending on the initial phase of the stimulus application. When a three-cycle stimulus is centered near the nadir of the temperature cycle, large phase shifts are achieved via amplitude suppression. However, when this stimulus is centered away from the temperature nadir, smaller phase shifts are achieved in which both small increases and small decreases in circadian amplitude are observed. These data indicate that the human circadian pacemaker is not a simple, phase-only oscillator. Instead, a full description of human circadian resetting responses to light requires analysis of both phase and amplitude data--a finding that is consistent with a phase-amplitude model of the circadian resetting mechanism.

Adolescent↗
PubMed1994

Sensitivity of the human circadian pacemaker to moderately bright light.

The aim of the present study was to evaluate the sensitivity of the human circadian pacemaker to the resetting effect of moderately bright light (approximately 1260 lux), and to assess the direct effect of such light exposure by comparison to a control group of subjects undergoing the same behavioral manipulations but with a similarly timed exposure to darkness instead of light. Endogenous circadian phase and amplitude were assessed in dim light (approximately 10-15 lux) before and after two consecutive series of three 5-hr exposures to approximately 1260 lux or to darkness (approximately 0.03 lux) in two different groups of young healthy men, using the constant-routine technique. The light or darkness exposure was centered 1.5 hr after the initial fitted endogenous temperature minimum and 12 hr opposite the newly scheduled midpoint of the sleep episode, in order to induce a phase advance in the light-exposed subjects. The phase of the endogenous circadian pacemaker was assessed by a dual-harmonic regression model from core body temperature recorded every minute during constant routines. Urinary volume was measured at each micturition, subjective alertness every 20 min, and cognitive performance hourly. The endogenous circadian phase shifted to a significantly earlier time after each series of light exposures in the treatment group than it did in the control group (two-way analysis of variance for repeated measures: F = 67.91, p = 0.0001). The analysis of circadian curves of urine production, subjective alertness, and cognitive performance scores revealed that all variables maintained stable temporal relationships with the endogenous circadian temperature minimum--an indication that these rhythms shifted in the same direction and by an equivalent amount. Despite comparable behavioral schedules, including the timing of bedrest/sleep and social contacts, circadian temperature rhythm of control subjects free-ran under dim light conditions, indicating that moderately bright light exerted a direct biological effect on the human circadian pacemaker in the treatment group. The present study also demonstrated that light of approximately 1260 lux (which is of substantially lower intensity that the approximately 7000-12,000 lux used in prior experiments) produces robust phase advances of the endogenous circadian temperature rhythm, which has been shown to be an accurate marker of the output of the circadian pacemaker (Czeisler et al., 1989). These results support the hypothesis that the phase-shifting effect of light on the human circadian pacemaker has a strongly nonlinear relationship to illuminance levels, such that it is preserved despite marked reductions in light intensity.

Adolescent↗
PubMed1997

The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats.

A 14-day orbital spaceflight was performed using ovariectomized Fisher 344 rats to determine the combined effects of estrogen deficiency and near weightlessness on tibia radial bone growth and cancellous bone turnover. Twelve ovariectomized rats with established cancellous osteopenia were flown aboard the space shuttle Columbia (STS-62). Thirty ovariectomized rats were housed on earth as ground controls: 12 in animal enclosure modules, 12 in vivarium cages, and 6 killed the day of launch for baseline measurements. An additional 18 ovary-intact rats were housed in vivarium cages as ground controls: 8 rats were killed as baseline controls and the remaining 10 rats were killed 14 days later. Ovariectomy increased periosteal bone formation at the tibia-fibula synostosis; cancellous bone resorption and formation in the secondary spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA) levels for the prepro-alpha2(1) subunit of type 1 collagen, osteocalcin, transforming growth factor-beta, and insulin-like growth factor I in the contralateral proximal tibial metaphysis and for the collagen subunit in periosteum pooled from tibiae and femora and decreased cancellous bone area. Compared to ovariectomized weight-bearing rats, the flight group experienced decreases in periosteal bone formation, collagen subunit mRNA levels, and cancellous bone area. The flight rats had a small decrease in the cancellous mineral apposition rate, but no change in the calculated bone formation rate. Also, spaceflight had no effect on cancellous osteoblast and osteoclast perimeters or on mRNA levels for bone matrix proteins and signaling peptides. On the other hand, spaceflight resulted in an increase in bone resorption, as ascertained from the diminished retention of a preflight fluorochrome label. This latter finding suggests that osteoclast activity was increased. In a follow-up ground-based experiment, unilateral sciatic neurotomy of ovariectomized rats resulted in cancellous bone loss in the unloaded limb in excess of that induced by gonadal hormone deficiency. This additional bone loss was arrested by estrogen replacement. We conclude from these studies that estrogen alters the expression of signaling peptides believed to mediate skeletal adaptation to changes in mechanical usage and likewise modifies the skeletal response to mechanical unloading.

Animals↗
PubMed1993

A reevaluation of the vestibulo-ocular reflex: new ideas of its purpose, properties, neural substrate, and disorders.

Conventional views of the vestibulo-ocular reflex (VOR) have emphasized testing with caloric stimuli and by passively rotating patients at low frequencies in a chair. The properties of the VOR tested under these conditions differ from the performance of this reflex during the natural function for which it evolved--locomotion. Only the VOR (and not visually mediated eye movements) can cope with the high-frequency angular and linear perturbations of the head that occur during locomotion; this is achieved by generating eye movements at short latency (< 16 msec). Interpretation of vestibular testing is enhanced by the realization that, although the di- and trisynaptic components of the VOR are essential for this short-latency response, the overall accuracy and plasticity of the VOR depend upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously encode inputs from the labyrinthine semicircular canals and otoliths, as well as from the visual and somatosensory systems. The central vestibular pathways branch to contact vestibular cortex (for perception) and the spinal cord (for control of posture). Thus, the vestibular nuclei basically coordinate the stabilization of gaze and posture, and contribute to the perception of verticality and self-motion. Consequently, brainstem disorders that disrupt the VOR cause not just only nystagmus, but also instability of posture (eg, increased fore-aft sway in patients with downbeat nystagmus) and disturbance of spatial orientation (eg, tilt of the subjective visual vertical in Wallenberg's syndrome).

Brain Diseases↗
PubMed1997

Prostaglandin E2 (PGE2) and risedronate was superior to PGE2 alone in maintaining newly added bone in the cortical bone site after withdrawal in older intact rats.

The objects of this study were (1) to determine the effects of risedronate (Ris) and prostaglandin E2 (PGE2) alone and in combination, on tibial diaphyses of older intact female rats; and (2) to observe the fate of any extra bone if formed after withdrawal of the treatment. Nine-month-old female Sprague-Dawley rats were treated with 6 mg of PGE2/kg/day, 1 or 5 micrograms of Ris/kg twice a week, or 6 mg of PGE2/kg/day plus 1 or 5 micrograms of Ris/kg twice a week for the first 60 days and followed by vehicle injections for another 60 days. Cross-sections of double fluorescent labeled, undecalcified tibial diaphyses proximal to the tibiofibular junction were processed for histomorphometry. We found that: (1) neither the 1 microgram nor the 5 micrograms of Ris treatment in the 60-day on/60-day off group showed any histomorphometric differences from age-related controls; (2) while the 60 days of PGE2 treatment added extra cortical bone (6%) on the tibial shaft (due to stimulation of periosteal, endocortical, and marrow trabecular bone formation), the new endocortical and most of the new marrow trabecular bone were lost when treatment was withdrawn; however, the new periosteal bone remained; (3) PGE2 with Ris added the same amount of new bone to tibial diaphysis as did PGE2 alone and upon withdrawal, new marrow trabecular bone was lost but new periosteal and endocortical bones were preserved in PGE2 + 1 microgram of Ris on/off group. In contrast, all the new bone was maintained in the PGE2 + 5 micrograms of Ris on/off group; (4) PGE2 + Ris cotreatment failed to block the increase in cortical bone porosity induced by PGE2; and (5) in the PGE2 alone and PGE2 + 1 microgram of Ris on/off groups bone turnover was higher than that in the PGE2 + 5 micrograms of Ris on/off group. These results indicate that on/off treatment with PGE2 and Ris is superior to PGE2 alone in that it forms the same amount of new bone during treatment, but preserves more cortical bone during withdrawal. Depression of bone resorption and turnover were the tissue mechanisms responsible for this protection.

Age Factors↗
PubMed1997

Prostaglandin E2 increases the skeletal response to mechanical loading.

The study tested the influence of prostaglandin E2 (PGE2) on the skeletal response to increased in vivo mechanical loading through a four-point bending device. One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/- 34 g) were divided into 12 groups to accommodate all possible combinations of doses of loads (25, 30, or 35 N) and PGE2 (0, 0.1, 0.3, or 1 mg/kg). Rats received subcutaneous injections of PGE2 daily and in vivo loading of the right tibia every Monday, Wednesday, and Friday for four weeks. Histomorphometric analysis of the periosteal and endocortical surfaces following in vivo dual fluorochrome labeling was performed on both the loaded region of the right tibial diaphysis and a similar region of the left tibial diaphysis. Without PGE2, the threshold for loading to stimulate bone formation was 30 N (peak strain 1360 mu epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the endocortical surface. Without loading, the minimum dose of PGE2 to stimulate bone formation at all surfaces was 1 mg/kg/day. When 1 mg/kg/day PGE2 was combined with the minimum effective load, an additive effect of PGE2 and loading on bone formation was observed at the endocortical surface, but a synergistic effect was noted at the periosteal surface. No combined effect of ineffective doses of loading and PGE2 was found. A synergistic effect at peak strains of approximately 1625 mu epsilon on the periosteal surface could suggest either the involvement of locally produced growth factors or autoregulation of endogenous synthesis of PGE2 by exogenously administered PGE2.

Animals↗
PubMed1993

Acclimatization and tolerance to extreme altitude.

During the last ten years, two major experiments have elucidated the factors determining acclimatization and tolerance to extreme altitude (over 7000 m). These were the American Medical Research Expedition to Everest, and the low pressure chamber simulation, Operation Everest II. Extreme hyperventilation is one of the most important responses to extreme altitude. Its chief value is that it allows the climber to maintain an alveolar PO2 which keeps the arterial PO2 above dangerously low levels. Even so, there is evidence of residual impairment of central nervous system function after ascents to extreme altitude, and maximal oxygen consumption falls precipitously above 7000 m. The term 'acclimatization' is probably not appropriate for altitudes above 8000 m, because the body steadily deteriorates at these altitudes. Tolerance to extreme altitude is critically dependent on barometric pressure, and even seasonal changes in pressure probably affect climbing performance near the summit of Mt Everest. Supplementary oxygen always improves exercise tolerance at extreme altitudes, and rescue oxygen should be available on climbing expeditions to 8000 m peaks.

Acclimatization↗
PubMed1990

Collagen in the spicule organic matrix of the gorgonian Leptogorgia virgulata.

Decalcification of the calcareous spicules from the gorgonian Leptogorgia virgulata reveals an organic matrix that may be divided into water insoluble and soluble fractions. The insoluble fraction displays characteristics typical of collagen, which is an unusual component of an invertebrate calcium carbonate structure. This matrix fraction exhibits a collagenous amino acid profile and behavior upon SDS-PAGE. Furthermore, the reducible crosslink, dihydroxylysinonorleucine (DHLNL), is detected in this fraction. The composition of the matrix varies seasonally; i.e., the collagenous composition is most prevalent in the summer. These results indicate that the insoluble matrix is a dynamic structure. Potential roles of this matrix in spicule calcification are discussed.

Amino Acids↗
PubMed1993

Salivary total protein and experimental Coriolis sickness.

Symptomatic reporting has been used in quantifying the severity of motion sickness including Coriolis sickness. This study was designed to objectively examine if the dynamic changes of salivary protein concentration relate to the severity of Coriolis sickness. Healthy adults with normal vestibular function underwent a modified Coriolis Sickness Susceptibility Index (CSSI) test, utilizing a staircase profile. Salivary samples were obtained prior to stimulation, 15, 30, and 45 min following stimulus onset, and/or upon reaching "nausea-II" endpoint. Total protein concentration tended to rise over the initial 30 min of stimulation, and then level off or decline. A statistically significant difference was found between the pre-stimulation and 30 min samples. Although some variability existed among the subjects, the general pattern of changes along the time course was similar. An inverse correlation approaching statistical significance was found between control (non-stimulus) total protein levels, and minutes of Coriolis stimulation required to reach the "nausea-II" endpoint. Thus, baseline salivary total protein levels can be of use in predicting susceptibility of Coriolis sickness and other forms of motion sickness.

Adult↗
PubMed1993

Human vertical eye movement responses to earth horizontal pitch.

The vertical eye movements in humans produced in response to head-over-heels constant velocity pitch rotation about a horizontal axis resemble those from other species. At 60 degrees/s these are persistent and tend to have non-reversing slow components that are compensatory to the direction of rotation. In most, but not all subjects, the slow component velocity was well characterized by a rapid build-up followed by an exponential decay to a non-zero baseline. Super-imposed was a cyclic or modulation component whose frequency corresponded to the time for one revolution and whose maximum amplitude occurred during a specific head orientation. All response components (exponential decay, baseline and modulation) were larger during pitch backward compared to pitch forward runs. Decay time constants were shorter during the backward runs, thus, unlike left to right yaw axis rotation, pitch responses display significant asymmetries between paired forward and backward runs.

Adult↗
PubMed1993

Polyamines in the lateral vestibular nuclei of the squirrel monkey and their potential role in vestibular compensation.

Polyamine synthesis increases in response to injurious stimuli including axotomy and denervation. Reduced eye nystagmus and head-deviation have been observed in unilateral labyrinthectomized (UL) guinea pigs treated with an inhibitor of polyamine synthesis, alpha-difluoromethylornithine (DFMO). We quantified polyamines in the lateral vestibular nuclei (LVN) of control and UL squirrel monkeys during the phase of vestibular compensation (VC) and performed an experiment to determine if DFMO reduces nystagmus previously observed in the guinea pig. Polyamines were detected in the LVN of control and UL squirrel monkeys. Putrescine and spermidine increased in the ipsilateral LVN 3 days after UL with no change in the contralateral LVN. No left-right differences were noted in the 5-day post-UL monkey. DFMO reduced nystagmus in a UL squirrel monkey. These findings suggest that polyamines are important in vestibular function and may contribute to nystagmus observed in VC.

Animals↗