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Background: The Substance Abuse and Mental Health Administration (SAMHSA) has invested substantial resources in Certified Community Behavioral Health Centers (CCBHCs) to integrate mental health and addiction treatment and to address the nation's epidemic of opioid-related morbidity and mortality., Methods: Using an audit or "secret shopper" method, we surveyed 311 CCBHCs listed in SAMHSA's Behavioral Health Treatment Services Locator to identify the proportion of centers that offer buprenorphine and/or methadone treatment and the proportion of these that offer a prescriber visit during patients' first visit to the center., Results: We received responses from 82.6% (n = 257) of the CCBHCs that we attempted to contact. Of those contacted, 33.9% said they offered agonist therapy, 33.5% said they could refer patients to a buprenorphine or methadone provider, and 32.7% said they could neither offer nor refer patients for agonist therapy. Of the agencies contacted, only 2.7% could confirm the availability of a prescriber visit at the patient's first visit to the CCBHC., Conclusions: Despite significant federal investment to integrate addiction and mental health treatment in CCBHCs, CCBHCs have not generally become providers of low-threshold buprenorphine and/or methadone treatment for opioid use disorder. Policy-makers should consider how to better incentivize low-threshold access to buprenorphine and methadone treatment in the nation's network of CCBHCs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to determine the frequency of translocations and insertions in the blood of long-term pilots in relation to estimated cumulative radiation dose received while flying, and to compare that to the frequency in a group of similarly aged men without a history of frequent airline travel., Methods: Healthy, non-smoking male pilots aged 40-60 yr were recruited from a single airline. Non-pilot controls were recruited from healthy, non-smoking professional males in the same age range and without a history of frequent flying. Eligibility was determined based on screening surveys. Career pilot radiation doses were calculated individually using airline flight profiles, personal flight history, and the CARI computer program. Translocation frequency was determined using fluorescence in situ hybridization., Results: Blood samples for chromosome analysis were provided by 19 individuals. The mean number of metaphases counted per subject was 2802 in the pilots and 3000 in the controls. The mean number of translocations per cell (genome equivalent) was significantly higher among the pilots (mean +/- SE; 0.0031 +/- 0.0008) than among the controls (0.0010 +/- 0.0003) (p = 0.03, Mann-Whitney U test). However, within the 26 to 72 millisievert range encountered in this study, observed values among the pilots did not follow the dose-response pattern expected based on available models for chronic low dose radiation exposure., Conclusions: There was a statistically significant higher number of translocations per cell among pilots than among controls, although the expected dose-response relationship for radiation was not observed among the pilots.

Background: The airline pilot works within a complex exposure environment that may present physiological challenges to long-term health., Methods: This study investigated self-reported disease outcomes among a large group of active and retired commercial airline pilots in the United States and Canada. A survey methodology was used, including the collection of historical information., Results: Of 10,678 surveys mailed, 6609 were returned (6533 men, 63 women). Given the limitations of survey methodology, increased disease rates among pilots were suggested for melanoma, motor neuron disease, and cataracts. However, rates for other diseases were in general lower than those for the U.S. population., Conclusions: Further study has been initiated to verify and follow reported cases, to expand the study to a larger group, and to collect more in-depth information on flight histories, occupational exposures, and lifestyle factors.

Lower body negative pressure (LBNP; -5 and -15 mmHg) was applied to 14 men (mean age 44 yr) to test the hypothesis that reductions in preload without effect on stroke volume or blood pressure increase selectively muscle sympathetic nerve activity (MSNA), but not the ratio of low- to high-frequency harmonic component of spectral power (P(L)/P(H)), a coarse-graining power spectral estimate of sympathetic heart rate (HR) modulation. LBNP at -5 mmHg lowered central venous pressure and had no effect on stroke volume (Doppler) or systolic blood pressure but reduced vagal HR modulation. This latter finding, a manifestation of arterial baroreceptor unloading, refutes the concept that low levels of LBNP interrogate, selectively, cardiopulmonary reflexes. MSNA increased, whereas P(L)/P(H) and HR were unchanged. This discordance is consistent with selectivity of efferent sympathetic responses to nonhypotensive LBNP and with unloading of tonically active sympathoexcitatory atrial reflexes in some subjects. Hypotensive LBNP (-15 mmHg) increased MSNA and P(L)/P(H), but there was no correlation between these changes within subjects. Therefore, HR variability has limited utility as an estimate of the magnitude of orthostatic changes in sympathetic discharge to muscle.

Mechanisms responsible for presyncope during lower body negative pressure (LBNP) in otherwise healthy subjects are poorly understood. Muscle sympathetic nerve activity (MSNA), blood pressure, heart rate (HR), HR power spectra, central venous pressure (CVP) and stroke volume were determined in 14 healthy men subjected to incremental LBNP. Of these, seven experienced presyncope at LBNP >-15 mmHg. Subjects who tolerated LBNP >-15 mmHg had significantly lower CVP (2.6+/-1.0 versus 7.2+/-1.2 mmHg; means+/-S.E.M., P<0.02), HR (59+/-2 versus 66+/-3 beats/min, P<0.05) and MSNA burst frequency (29.0+/-2.4 versus 39.0+/-3.5 bursts/min, P<0.05) during supine rest. LBNP at -15 mmHg had no effect on blood pressure, but caused similar and significant reductions in stroke volume and cardiac output in both groups. Subjects who tolerated LBNP had significant reflex increases in HR, MSNA burst frequency and burst amplitude with LBNP of -15 mmHg. These responses were absent in those who experienced presyncope. The gain of the cardiac baroreflex regulation of MSNA was markedly attenuated in pre-syncopal subjects (1.2+/-0.6 versus 8.8+/-1.4 bursts/100 heart beats per mmHg; P<0.001). Healthy subjects who experience presyncope in response to LBNP appear more dependent, when supine, upon MSNA to maintain preload, and less able to increase sympathetic vasoconstrictor discharge to skeletal muscle reflexively in response to orthostatic stimuli.

The airline pilot operates within an environment that consists of circadian dysrhythmia, reduced atmospheric pressure, mild hypoxia, low humidity, and exposure to sound, vibration, cosmic-radiation, and magnetic-field exposure. These occupational exposures present physiological challenges to the long term health of the airline pilot. In particular, exposure to cosmic radiation and its carcinogenic potential have recently received considerable attention. Given the complexity of the environment and possible synergistic exposures, there is an immediate requirement for comprehensive research into both cosmic-radiation and magnetic-field exposures in airline pilots. In response, the Airline Pilots Association International in conjunction with the Medical University of South Carolina (Department of Biometry and Epidemiology) has initiated an extensive research program into these occupational exposures. These investigations include ground based calculations, flight-dose estimates, epidemiological survey and exposure assessment, and biological marker analysis.

Background: Airline pilots are exposed to magnetic fields generated by the aircraft's electrical system. The objectives of this study were (1) to directly measure flight deck magnetic fields in terms of personal exposure to the pilots when flying on different aircraft types over a 75-hour flight-duty month, and (2) to compare magnetic field exposures across flight deck types and job titles., Methods: Measurements were taken using personal dosimeters carried by either the Captain or the First Officer on Boeing 737/200, Boeing 747/400, Boeing 767/300ER, and Airbus 320 aircraft., Results: Approximately 1,008 block hours were recorded at a sampling frequency of 3 seconds. Total block time exposure to the pilots ranged from a harmonic geometric mean of 6.7 milliGauss (mG) for the Boeing 767/300ER to 12.7 mG for the Boeing 737/200., Conclusions: Measured flight deck magnetic field levels were substantially above the 0.8-1 mG level typically found in the home or office and suggest the need for further study to evaluate potential health effects of long-term exposure., (Copyright 2000 Wiley-Liss, Inc.)

The concept that spectral analysis of heart rate variability (HRV) can estimate cardiac sympathetic nerve traffic in subjects with both normal and impaired left ventricular systolic function has not been validated against muscle sympathetic nerve activity (MSNA). We used coarse-graining spectral analysis to quantify the harmonic and non-harmonic, or fractal, components of HRV and to determine low-frequency (0.0-0.15 Hz; PL) and high-frequency (0.15-0.5Hz; PH) harmonic power. To test the hypothesis that MSNA and HRV representations of sympathetic nerve activity (PL and PL/PH) increase in parallel in heart failure, we recorded heart rate and MSNA during supine rest in 35 patients (age 52.4+/-2 years; mean+/-S. E.M.), with a mean left ventricular ejection fraction of 22+/-2%, and in 34 age-matched normal subjects. Power density was log10 transformed. Mean MSNA was 52.9+/-2.6 bursts/min in heart failure patients and 34.9+/-1.9 bursts/min in normal subjects (P<0.0001). In normal subjects, but not in heart failure patients, total power (PT) (r=-0.41; P=0.02) and fractal power (PF) (r=-0.36; P=0.04) were inversely related to age. In heart failure patients, total and fractal power were reduced (P<0.009 for both), and were inversely related to MSNA burst frequency (r=-0.55, P=0.001 and r=-0.60, P=0. 0003 respectively). In normal subjects, there was no relationship between MSNA and either PL or PH. In heart failure patients, as anticipated, PH was inversely related to MSNA (r=-0.41; P<0.02). However, PL was also inversely rather than directly related to MSNA (r=0.44 for 1/log10 PL; P<0.01). There was no relationship between other sympathetic (PL/PH) or parasympathetic (PH/PT) indices and MSNA in either heart failure patients or normal subjects. The lack of concordance between these direct and indirect estimates of sympathetic nervous system activity indicates that this component of HRV cannot be used for between-subject comparisons of central sympathetic nervous outflow. It is the absence of low-frequency power that relates most closely to sympathetic activation in heart failure.

Background: Flight crews are exposed to elevated levels of cosmic radiation and to magnetic fields generated by the aircraft's electrical system. The purpose of this study was to quantify these two occupational exposures., Methods: Magnetic fields were measured during 37 flights (23 in the cockpit and 14 in the cabin) using an Emdex Lite personal dosimeter. All cockpit measurements were taken on the B737/200. Cabin measurements were taken in several aircraft types, including the B737, B757, DC9, and L1011. Cosmic radiation was computer estimated for 206 flights using the Federal Aviation Administration's program CARI-3C., Results: Magnetic field levels in the cockpit had a mean value of approximately 17 milliGauss (mG), while cabin measurements were lower (mean values of approximately 3 or less in economy, 6 in first class, 8 in front serving areas). Cosmic radiation equivalent dose rates to bone marrow and skeletal tissue ranged from 0.3 to 5.7 microsieverts per hour., Conclusions: Elevated magnetic field levels in front serving areas and the cockpit suggest the need for further study to evaluate long-term exposure to flight crew members who work in these areas. Cosmic radiation levels are well below occupational limits for adults, but may require some pregnant flight crew members to adjust their flying time or routes.

1. There is a substantial non-harmonic or fractal component to the variability of both heart rate and blood pressure in normal subjects. Heart rate is the more complex of these two signals, with respect to the slope, beta, of the 1/f beta relationship. In congestive heart failure, heart rate spectral power is attenuated, but the fractal and harmonic components of heart rate and systolic blood pressure variability have not been characterized. 2. Two groups, each comprising 20 men, were studied during 15 min of supine rest and spontaneous respiration: one with functional class II-IV heart failure (age 52 +/- 2 years; mean +/- SEM) and a second group of healthy men (age 46 +/- 2 years). 3. Total spectral power for heart rate was significantly reduced in heart failure (P < 0.02), whereas total spectral power for systolic blood pressure was similar in the two groups. In both heart failure and normal subjects, 65-80% of total spectral power in these two signals displayed fractal characteristics. 4. In heart failure, the slope of the 1/f beta relationship for heart rate was significantly steeper than in normal subjects (1.40 +/- 0.08 compared with 1.14 +/- 0.05; P < 0.05), indicating reduced complexity of the fractal component of heart rate variability. There was no significant difference in the 1/f beta slope for systolic blood pressure variability between these two groups, but the blood pressure signals were less complex than heart rate variations in both heart failure (2.31 +/- 0.15; P < 0.006) and normal subjects (2.47 +/- 0.15; P < 0.0001). 5. Parasympathetic nervous system activity, as estimated from heart rate variability was reduced (P < 0.01) in patients with heart failure, whereas trends towards increased sympathetic nervous system activity and decreased non-harmonic power were not significant. 6. The non-harmonic components of cardiac frequency are reduced in heart failure. Non-harmonic power is not attenuated, but the complexity of the heart rate signal is less than in subjects with normal ventricular function. A reduction in parasympathetic modulation appears to contribute to this loss of complexity of heart rate. Consequently, the heart rate signal comes to resemble that of blood pressure. In contrast, the variability and complexity of the systolic blood pressure signal is similar in heart failure and normal subjects. This reduced complexity of heart rate variability may have adverse implications for patients with heart failure.

The purpose of these experiments was to compare the effects of endopeptidase inhibition with oral candoxatril on systemic and forearm hemodynamics and muscle sympathetic nerve activity with responses to a low-dose atrial natriuretic factor infusion. Eleven healthy men received at random on three separate days either intravenous saline, natriuretic factor (1.6 pmol/kg per minute) plus saline, or oral candoxatril (200 mg) plus saline. Measurements were made at baseline and 30, 60, and 90 minutes after interventions. Atrial natriuretic factor lowered diastolic pressure (P < .01), central venous pressure (P < .001), forearm blood flow (P < .05), and forearm vascular compliance (P < .05) but had no effect on systolic pressure, heart rate or its variability, stroke volume, sympathetic nerve activity, plasma norepinephrine, or endothelin-1. Plasma epinephrine increased (P < .01). Candoxatril lowered central venous pressure (P < .001) and increased systolic pressure (from 116 +/- 6 to 120 +/- 7 mm Hg; P < .05), endothelin (from 4.6 +/- 1.1 to 6.8 +/- 3.2 pmol/L; P < .02), and epinephrine (P < .05), without affecting any other variables. Candoxatril and atrial natriuretic factor lowered central venous pressure in healthy men without causing a reflex increase in sympathetic nerve activity or norepinephrine, yet epinephrine rose. This suggests that both interventions may specifically inhibit sympathetic nerve traffic to muscle at physiological plasma atrial natriuretic factor concentrations. However, whereas the peptide lowered blood pressure, candoxatril increased systolic pressure. These contrasting hemodynamic responses may be related to differences in plasma atrial natriuretic peptide concentration and to altered endothelin metabolism by candoxatril.

Our objective in these experiments was to evaluate the effects of atrial natriuretic factor on the gain of the spontaneous baroreceptor-heart rate reflex in humans. On two separate study days, we gave either atrial natriuretic factor during supine rest (16 nmol over 3 minutes, then 16 pmol/kg per minute) or saline (as vehicle) to nine healthy men (age, 23 +/- 1 years; mean +/- SEM) according to a random, double-blind design. Beat-by-beat RR interval and systolic pressure were recorded noninvasively. Sequences during which systolic pressure and the RR interval of the following beat changed in parallel (either increasing [Up] or decreasing [Down]) over at least three consecutive beats were identified and classified as baroreceptor-heart rate reflex sequences. Regression lines relating RR interval to the preceding systolic pressure were derived for each individual sequence. The mean value of the slopes of these regression lines was calculated to obtain the mean spontaneous baroreflex sensitivity for heart rate for each subject. Saline infusion did not change RR interval, systolic pressure, or number of baroreflex sequences nor the slope of the mean spontaneous baroreflex sensitivity for heart rate or slopes of Up or Down sequences. Atrial natriuretic factor, at a dose that lowers central venous pressure, did not affect systolic pressure, respiratory rate, or the number of baroreflex sequences but reduced RR interval from 952 +/- 35 to 930 +/- 40 ms (P < .04) and the mean slope of spontaneous baroreflex sensitivity for heart rate from 32.7 +/- 4.8 to 23.1 +/- 2.8 ms.mm Hg-1 (P < .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: Our objective was to determine whether continuous positive airway pressure augments the low heart rate variability of congestive heart failure, a marker of poor prognosis., Background: Nasal continuous positive airway pressure improves ventricular function in selected patients with heart failure., Methods: In 21 sessions in 16 men (mean [+/- SE] age 56 +/- 2 years) with New York Heart Association functional class II to IV heart failure, we assessed the effects of 45 min with (n = 14) and without (as a time control, n = 7) nasal continuous positive airway pressure (10 cm of water) on heart rate variability and end-expiratory lung volume. Coarse-graining spectral analysis was used to derive total spectral power (PT), its nonharmonic component (fractal power [PF]) and the low (0.0 to 0.15 Hz [PL]) and high (0.15 to 0.50 Hz [PH]) frequency components of harmonic power. Standard deviation of the RR interval, high frequency power and the PH/PT ratio were used to estimate parasympathetic activity in the time and frequency domains, and the PL/PH ratio was used to estimate cardiac sympathetic activity in the frequency domain., Results: Use of continuous positive airway pressure increased end-expiratory lung volume by 445 +/- 82 ml (p < 0.01) and both time (p < 0.006) and frequency domain indexes of heart rate variability: Total spectral power (p < 0.01), nonharmonic power (p < 0.023) and low (p < 0.04) and high (p < 0.05) frequency components of harmonic power all increased. Time alone had no effect on these variables. By comparison, the PH/PT ratio increased during nasal continuous positive airway pressure (p < 0.004), whereas the PL/PH ratio was unchanged. Breathing rate remained constant in both groups., Conclusions: Short-term application of nasal continuous positive airway pressure increases heart rate variability and time and frequency domain indexes of parasympathetic activity without influencing cardiac sympathetic activity. This increase may occur reflexively, through stimulation of pulmonary mechanoreceptor afferents.

To study the effects of atrial natriuretic factor (ANF) on sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) control of heart rate, we gave ANF (50 micrograms over 3 min, then 50 ng.kg-1.min-1) and saline (vehicle) to six normal men [age 22 +/- 2 (SE) yr] during supine rest on two separate study days according to a random double-blind design. R-R interval data were sampled at 1,000 Hz over 7-min time segments, then analyzed by coarse graining spectral analysis of heart rate variability (HRV) to yield indicators of PNS and SNS activity. From the harmonic component of HRV, the integrated power in the low-frequency region (0.0-0.15 Hz, PL) and in the high-frequency region (0.15-0.50 Hz, PH) were calculated. Total spectral power (PT) was obtained and used to normalize the PNS indicator as PH/PT. The quantity PL/PH was taken as an indicator of SNS activity. By the 20th min of its infusion, ANF lowered PT, PH, and the SNS indicator (4.20 +/- 1.9 to 2.37 +/- 0.65; P < 0.05) but did not significantly change the PNS indicator (PH/PT). In contrast, 20-min saline infusion had no effect on these variables. These observations are consistent with our previous documentation of a relative sympathoinhibitory action of ANF on muscle sympathetic nerve activity and support the concept that ANF acts on the autonomic nervous system to decrease sympathetic outflow.

We have shown previously that the heart rate variability (HRV) signal is fractal in nature with a high degree of complexity, as given by the calculated fractal dimension (DF). We have also reported that loss of complexity, as indicated by a reduction in DF of HRV, is associated with orthostatic hypotension and impending syncope. To extend this investigation of cardiovascular responses, we have investigated the signal characteristics of short-term systolic blood pressure variability (BPV) coincident with measurements of HRV during orthostatic stress. Eight healthy men completed a test protocol of 20 min supine rest followed sequentially by 10 min at each of -5, -15, -25, -40, and -50 mmHg lower body negative pressure (LBNP) and 10 min supine recovery. We found that resting BPV and HRV were fractal with approximately 70% of both variables in the fractal component of the variability signal. The slope of the 1/f beta relationship was 1.16 +/- 0.12 for HRV and 2.31 +/- 0.17 for BPV. With increasing levels of orthostatic stress, the 1/f beta slope of HRV increased significantly to 1.68 +/- 0.08 at -50 mmHg LBNP, whereas the 1/f beta slope was unchanged for BPV. Indicators of parasympathetic and sympathetic nervous system activity derived from heart rate variability suggested reduced and increased values, respectively, as the LBNP increased. These data indicate important differences in heart rate and blood pressure control under orthostatic stress.

Exposure to microgravity with space flight, or to earth-based analogs such as head-down tilt (HDT) bedrest, results in cardiovascular deconditioning. With reapplication of gravity, deconditioning is most often observed as an elevated heart rate, a narrowed pulse pressure, and possibly even a failure to maintain blood pressure with symptoms of presyncope or syncope. Noninvasive measurements of heart rate variability (HRV) have been used to study cardiovascular control mechanisms during orthostatic stress (head-up tilt and lower body negative pressure [LBNP]). Recently, the authors developed a new approach to study heart rate and blood pressure control mechanisms. Coarse graining spectral analysis (CGSA) allows simultaneous extraction of not only parasympathetic (PNS) and sympathetic (SNS) indicators from the HRV signal, but also determines the fractal dimension (DF), calculated from the slope (beta) of the log spectral power-log frequency relationship. The fractal dimension is an index of the complexity of the cardiovascular control system. Our investigations have indicated patterns of HRV consistent with reduced PNS and increased SNS activity and reduced DF with the HRV signal during orthostatic stress. These findings also indicate that the cardiovascular system may be less stable when operating at a reduced level of complexity.

The effects of 28 days continuous 6 degrees head-down tilt bed-rest on heart rate variability and the slope of the spontaneous arterial baroreflex were evaluated during supine rest and the first 10 min of 60 degrees head-up tilt. Twelve healthy men were assigned to either a no counter-measure (No-CM), or a counter-measure (CM) group so that there was no difference in maximal oxygen uptake. Counter-measures consisted of short-term, high resistance exercise for 6 days per week from days 7-28, and lower body negative pressure (-28 mmHg) for 15 min on days 16, 18, 20 and 22-28. In spite of balanced between-group fitness, mean RR-interval was different between the No-CM and the CM group prior to bed-rest, but neither this nor any other variables showed significant counter-measure by bed-rest interaction effects. Therefore, all data presented are from the main effects of bed-rest or tilt from the analysis of variance. RR-interval was reduced significantly by bed-rest and by tilt (P < 0.0001). Indicators from spectral analysis of heart-rate variability suggested reduced parasympathetic nervous system activity with bed-rest (P < 0.01) and head-up tilt (P < 0.05), and increased sympathetic nervous system activity after bed-rest (P < 0.01). An indicator of complexity of cardiovascular control mechanisms, taken from the slope (beta) of log spectral power vs. log frequency relationship, suggested reduced complexity with bed-rest (P < 0.05) and head-up tilt (P < 0.01). The spontaneous baroreflex slope was reduced significantly by bed-rest (P < 0.03) and by head-up tilt (P < 0.04). Taken together, these data support the concept of altered autonomic nervous system function in the aetiology of cardiovascular deconditioning with bed-rest or space travel; and it would appear that no benefit is derived from these specific counter-measures.

Heart rate variability (HRV) spectral analysis has been used as a tool for short-term assessment of parasympathetic (PNS) and sympathetic nervous system (SNS) control of heart rate. However, it has been suggested that the PNS and SNS indicators are superimposed on a broad-band noise spectrum in which the power spectral densities are inversely proportional to their frequency (1/f beta). In this study, we have used coarse-graining spectral analysis to extract the harmonic components for calculation of PNS and SNS indicators and to obtain the slope (beta) of the 1/f beta component to estimate fractal dimension (DF) of a trail of HRV. DF was regarded as an indicator of cardiovascular system complexity. Ten healthy young subjects (6 women and 4 men) were studied in supine rest and with sequential applications of four levels of lower body negative pressure (LBNP; -10, -20, -30, and -50 mmHg) and head-up tilt (HUT; 10, 20, 30, and 70 degrees). In the 20 tests, there were six occurrences of presyncopal symptoms that required the test to be terminated before the planned end point. At low levels of LBNP or HUT, arterial pulse pressure (PP) was not changed from rest, and calculated DF was very high (beta approximately 1.00). At the higher levels of LBNP and HUT, PP decreased. Coincident with this reduction in PP, PNS activity decreased, SNS activity increased, and DF was reduced, each with a significant linear relationship to the change in PP (PNS: r = 0.56; SNS: r = 0.57; DF: r = 0.70, P < 0.01). Each occurrence of presyncope was associated a low PNS indicator as well as DF < 2.50 (beta > or = 1.80). These data indicate that the cardiovascular system is operating at a reduced level of complexity and further suggest that reduced complexity might not be compatible with cardiovascular homeostasis.

The kinetics of oxygen uptake (VO2) were observed at the onset of submaximal cycling exercise in seven men and one woman [mean age 22.6 +/- 0.9 (SE) yr] in the upright and supine positions and the supine position with -40 mmHg lower body negative pressure (LBNP). There was no significant difference for peak VO2 and ventilatory threshold between the supine (3,081 +/- 133 and 1,954 +/- 138 ml/min, respectively) and the supine + LBNP positions (3,062 +/- 152 and 1,973 +/- 122 ml/min); however, both were reduced compared with upright exercise (3,483 +/- 200 and 2,353 +/- 125 ml/min). Kinetic analysis applied to six repetitions by each subject indicated a slowing from a mean total lag time (time required to achieve 63% of the difference in VO2 between baseline and new steady state) of 36.3 +/- 2.7 s in upright exercise to 44.1 +/- 3.5 s in the supine position. However, total lag time for the supine + LBNP position (36.0 +/- 2.8 s) did not differ from upright exercise but was significantly faster than supine exercise. These data have been interpreted in support of an O2 transport limitation to VO2 kinetics at the onset of supine exercise that is countered by LBNP, likely through a more rapid increase in perfusion to the exercising muscle at these submaximal work rates.

The spontaneous baroreflex response was evaluated during supine rest and head up tilt (60 degrees) before and immediately after a 28 day 6 degrees HDT bedrest in 6 healthy adult men (age 30-42 years). Sequences of 3 or more beats where RR-interval and systolic blood pressure changed in the same direction were used to evaluate baroreflex response slope (BRS). Prior to bedrest, the mean BRS and RR-interval were 18.0 +/- 3.9 ms/mm Hg and 926 +/- 61 ms at rest and 10.5 +/- 2.5 ms/mm Hg and 772 +/- 63 ms during the first 10 min of 60 degrees tilt. Following bedrest, these values changed to 15.6 +/- 2.7 ms/mm Hg and 780 +/- 53 ms at rest, and to 6.5 +/- 1.2 ms/mm Hg and 636 +/- 44 ms during tilt. Thus, (1) the spontaneous baroreflex can be evaluated in human subjects during experiments of orthostatic stress; (2) the baroreflex slope was reduced on going from supine to the head up tilt position; and (3) 28 days of bedrest reduced the spontaneous baroreflex slope.

Two hundred forty-four anemic hemodialysis patients were randomized into recombinant erythropoietin and placebo-treated groups during a 12-wk double-blind phase, followed by a 24-wk open-label period. Mean platelet count rose from the baseline value of 242 x 10(9)/L to 264 x 10(9)/L on day 5 of epoetin therapy (P < 0.001, paired t test). Mean platelet count peaked at 290 x 10(9)/L on day 40 and remained at a significantly elevated level below the peak thereafter. The peak platelet count did not exceed the normal range in a majority of cases. Platelet count was unaffected by placebo. Patients without an erythropoietic response during the first few weeks of therapy exhibited a rise in platelet count comparable to that in patients with a satisfactory erythropoiesis. Patients with low initial serum ferritin concentrations had baseline platelet counts comparable to those with normal or high ferritin values and showed a similar rise in platelet count during therapy. As a group, patients with baseline platelet counts above 400 x 10(9)/L showed no rise in platelet count, whereas those with normal or reduced platelet counts showed a marked thrombopoietic response to epoetin. Erythropoietin therapy did not significantly alter the incidence of blood access thrombosis when compared with placebo treatment.

Following space flight or head down tilt bed rest, cardiovascular deconditioning is often observed as a failure to maintain arterial blood pressure with symptoms of presyncope or syncope. LBNP can be used as a stressor of the cardiovascular system to observe the regulatory process. We have recently developed a new method to study cardiovascular control. Coarse graining spectral analysis (CGSA), allows simultaneous extraction of the harmonic components to evaluate sympathetic and parasympathetic nervous activities, and of the underlying complexity of the physiological response as given by the slope (beta) or fractal dimension (DF). The recognition that system complexity plays a major role in maintenance of cardiovascular stability is a relatively new concept. It was the purpose of the present study to examine the underlying complexity of heart rate and systolic blood pressure (SBP) variablities as indicated by the DF and power spectral analysis. Eight healthy men completed a test protocol of 20 min supine rest followed sequentially by 10 min at -5, -15, -25, -40, and -50 mmHg LBNP, and 10 min supine recovery. At rest, DF of R-R interval was 3.57 (beta = 1.56 +/- 0.12). There was a progressive decline in DF with LBNP, until at -50 mmHg, DF decreased to 1.2 (beta = 2.66 +/- 0.09). The DF for SBP was 1.3 (beta = 2.1 +/- 0.18) at rest, and was not significantly changed during LBNP. In the mid- and high-frequency ranges of the spectra, there was a moderately high degree of coherence between the variability in R-R interval and SBP. These findings indicate that short term SBP has a relatively low and unchanged complexity compared to heart rate. The changes in DF of heart rate variability were marked with increasing levels of LBNP. The results of this, and our previous study, indicate that a decline of DF to a critical level (near 1.4) is associated with orthostatic hypotension. These data show the utility of simple, non-invasive methods of data collection in conjunction with sophisticated data analysis techniques to point to possible mechanisms of orthostatic hypotension.

The cardiovascular responses to a 10-min 1.22 rad (70 degrees) head-up tilt orthostatic tolerance test (OST) was observed in eight healthy men following each of a 5-min supine baseline (control), 4 h of 0.1 rad (6 degrees) head-down tilt (HDT), or 4 h 0.52 rad (30 degrees) head-up tilt (HUT). An important clinical observation was presyncopal symptoms in six of eight subjects following 4 h HDT, but in no subjects following 4 h HUT. Immediately prior to the OST, there were no differences in heart rate, stroke volume, cardiac output, mean arterial pressure and total peripheral resistance for HDT and HUT. However, stroke volume and cardiac output were greater for the control group. Mean arterial pressure for the control group was less than HDT but not HUT. Over the full 10-min period of OST, the mean arterial pressure was not different between groups. Heart rate increased to the same level for all three treatments. Stroke volume decreased across the full time period for control and HDT, but only at 3 and 9 min for HUT. There was a higher total peripheral resistance in the HDT group than control or HUT. The pre-ejection period to left ventricular ejection time ratio was less in HDT than for control or HUT groups. These data indicate a rapid adaptation of the cardiovascular system to 4 h HDT that appears to be inappropriate on reapplication of a head to foot gravity vector. We speculate that the cause of the impaired orthostatic tolerance is decreased tone in venous capacitance vessels so that venous return is inadequate.

The dynamics of ventilation (VE), oxygen uptake (VO2), carbon dioxide output (VCO2), and heart rate (fc) were studied in 12 healthy young men during upright and supine exercise. Responses to maximal and to two different types of submaximal exercise tests were contrasted. During incremental exercise to exhaustion, the maximal work rate, VO2max, VEmax, fc,max, and ventilatory threshold were all significantly reduced in supine compared to upright exercise (P less than 0.01-0.001). Following step increases or decreases in work rate between 25 W and 105 W, both VO2 and VCO2 responded more slowly in supine than upright exercise. Dynamics were also studied in two different pseudorandom binary-sequence (PRBS) exercise tests, with the work rate varying between 25 W and 105 W with either 5-s or 30-s durations of each PRBS unit. In both of these tests, there were no differences caused by body position in the amplitude or phase shifts obtained from Fourier analysis for any observed variable. These data show that the body position alters the dynamic response to the more traditional step increase in work rate, but not during PRBS exercise. It is speculated that the elevation of cardiac output observed with supine exercise in combination with the continuously varying work-rate pattern of the PRBS exercise allowed adequate, perhaps near steady-state, perfusion of the working muscles in these tests, whereas at the onset of a step increase in work rate, greater demands were placed on the mechanisms of blood flow redistribution.

The dynamic response characteristics of the oxygen uptake (VO2) response were investigated during upright cycle ergometer exercise in six healthy male volunteers. The exercise test consisted of a pseudorandom binary sequence (PRBS) with 15 units per sequence, each unit 15 s long, for a total period of 225 s. Six identical sequences were completed in a single test session. Each subject exercised under both normoxic and hypoxic (FIO2 = 14%) conditions. VO2 was measured breath-by-breath. The data were analyzed in the frequency domain by Fourier analysis to yield amplitude and phase shift coefficients for the relationship between the input work rate and the output responses of VO2 and heart rate (HR). The amplitude of the VO2/work rate was significantly reduced by hypoxia compared to normoxia over a wide range of frequencies. The mean VO2 was not different between hypoxia and normoxia. The phase shift for the VO2/work rate response was significantly greater for hypoxia than normoxia. The amplitude of the HR/work rate relationship was not significantly altered by hypoxia; however, the mean HR was higher during hypoxia. The phase shift of the HR/work rate response was significantly different between hypoxia and normoxia only at certain frequencies. These data indicate that the effects of hypoxia on the cardiorespiratory response to exercise can be characterized by the use of PRBS exercise and Fourier analysis techniques. A significant reduction in the ability of the cardiorespiratory system to adapt to changes in work rate appears to be caused by a reduction in the arterial O2 content.

The cardiovascular responses to 4 h of 6 degrees head-down tilt (HDT) were compared to those of 4 h of 30 degrees head-up tilt (HUT) following a period of 1 h baseline in the 30 degrees HUT position. Eight healthy males completed each tilt position. Immediately on assuming HDT, heart rate decreased slightly from baseline, but did not differ from HUT. Stroke volume and cardiac output both increased significantly by as much as 54% and 26%, respectively, in the first minute of HDT. The difference between HDT and HUT was no longer present after 30 min. Mean arterial blood pressure was unchanged throughout 4 h or HUT or HDT. The ratio of pre-injection period to left ventricular ejection time was significantly decreased across all 4 h of HDT. Plasma volume was slightly elevated over the 4 h of HDT, while plasma hemoglobin concentration was significantly reduced. No evidence of a diuresis was found with 4 h HDT. Plasma catecholamines were not different between HDT and HUT. The present results show that the immediate transition from a HUT to a HDT position causes a dramatic change in cardiovascular variables. These changes are generally transient with baseline values resumed by many variables within 30 min of exposure to 6 degrees HDT.

The question "can the approach used for radiation protection standards, i.e., to extrapolate dose--response relationships to low doses, be applied to combustion pollutants?" provided a basis for discussion. The linear, nonthreshold model postulated by ICRP and UNSCEAR for late effects of ionizing radiation is described and discussed. The utility and problems of applying this model to the effects of air pollutants constitute the focus of this paper. The conclusion is that, in the absence of evidence to the contrary, one should assume the same type of dose--effect relation for chemical air pollutants as for ionizing radiation.