Short-term course of drinking in an untreated sample of at-risk drinkers.

OBJECTIVE: We know little about the short-term course of drinking, particularly the stability or instability of at-risk drinking in untreated drinkers. Because few at-risk drinkers obtain help for their drinking, it is important to understand the short-term fluctuations between at-risk drinking and full-fledged alcohol use disorders, as well as remission of at-risk drinking. METHOD: We used four waves of data (each 6 months apart) from a probability community sample of 733 at-risk drinkers in six states in the southern United States to determine variation in abstinence, drinking patterns and alcohol use disorders over a 2-year period. For this analysis, we excluded those who reported receiving services for drinking during the 2-year study period (retrospectively at baseline), leaving a sample size of 664 (444 male); 479 (306 male) completed all four interviews. RESULTS: Although the majority (88%) of the sample was nonabstinent throughout the study, we found significant decreases in average number of drinks per drinking day and recent (past 6 months) alcohol disorders, and an increase in 6-month abstinence. Almost 30% of those with no recent alcohol disorder at baseline (n = 280) later met diagnostic criteria in at least one interview. Of those with a recent alcohol disorder at baseline (n = 199), one third met criteria in at least two subsequent interviews. CONCLUSIONS: There is some evidence for short-term progression from at-risk drinking to alcohol disorder. However, there is stronger evidence for declining problems and a fluctuation in and out of recovery and relapse, which may reflect an effort to maintain controlled drinking. Understanding this short-term course is important for primary and secondary prevention efforts and for screening of at-risk drinking in primary care and in the workplace.

Body temperature and thermoregulation during submaximal exercise after 115-day spaceflight.

BACKGROUND: Altered thermoregulation has been reported following spaceflight simulations (bed rest and water immersion) but has never been examined after actual spaceflight. HYPOTHESIS: We tested the null hypothesis that body temperatures and heat loss responses during exercise would be similar before and after spaceflight. METHODS: Two male crewmembers of the 115-d Mir 18 mission performed supine submaximal cycle exercise (20 min at 40% and 20 min at 65% of preflight VO2peak) once at 145-146 d preflight and once at 5 d postflight (R + 5). RESULTS: After flight neither crewmember could complete the exercise protocol, stopping after 28-29 min. The core temperature (Tin, ingestible telemetry pill) at test termination was similar (37.8 degrees C for both subjects) pre- and postflight despite shorter postflight test duration. The slopes of the skin blood flow (laser Doppler)/Tin relationship (subject 1: 396 vs. 214; subject 2: 704 vs. 143% change Perfusion Unit/degree C), and the sweating rate (dew point hygrometry)/Tin relationship (subject 1: 6.3 vs. 2.0; subject 2: 4.6 vs. 0.7 mg.min-1.cm-2.degree C-1), were both reduced postflight without appreciable change in the Tin thresholds for sweating or skin blood flow. CONCLUSION: In this preliminary report for two crewmembers, the sensitivity of the heat loss responses were reduced after long-duration spaceflight, resulting in a faster rate of rise in core temperature.

Upright exercise or supine lower body negative pressure exercise maintains exercise responses after bed rest.

Adaptation to bed rest or space flight is accompanied by an impaired ability to exercise in an upright position. We hypothesized that a daily, 30-min bout of intense, interval exercise in upright posture or supine against lower body negative pressure (LBNP) would maintain upright exercise heart rate and respiratory responses after bed rest. Twenty-four men (31 +/- 3 yr) underwent 5 d of 6 degree head-down tilt: eight performed no exercise (CON), eight performed upright treadmill exercise (UPex), and eight performed supine treadmill exercise against LBNP at -51.3 +/- 0.4 mm Hg (LBNPex). Submaximal treadmill exercise responses (56, 74, and 85% of VO2peak) were measured pre- and post-bed rest. In CON, submaximal heart rate, respiratory exchange ratio, and ventilation were significantly greater (P < or = 0.05) after bed rest. In UPex and LBNPex, submaximal exercise responses were similar pre- and post-bed rest. Our results indicate that a daily 30-min bout of intense, interval upright exercise training or supine exercise training against LBNP is sufficient to maintain upright exercise responses after 5 d of bed rest. These results may have important implications for the development of exercise countermeasures during space flight.

Effect of fluid ingestion on orthostatic responses following acute exercise.

Orthostatic tolerance is impaired following an acute bout of exercise. This study examined the effect of fluid ingestion following treadmill exercise in restoring the cardiovascular responses to an orthostatic stress. Five men (age, 29.6 +/- 3.4 yrs) were exposed to a graded lower body negative (LBNP) pressure protocol (0 to -50 mmHg) during euhydration without exercise (C), 20 minutes after exercise dehydration (D), 20 minutes after exercise and fluid ingestion (FI20), and 60 minutes after exercise and fluid ingestion (FI60). Fluid ingestion (mean +/- SE) consisted of water-ingestion equivalent to 50% of the body weight lost during exercise (520 +/- 15 ml). Exercise dehydration resulted in significantly higher heart rates (119 +/- 8 vs 82 +/- 7 bpm), lower systolic blood pressures (95 +/- 1.7 vs 108 +/- 2.3 mmHg), a smaller increase in leg circumference (3.7 +/- 4 vs 6.9 +/- 1.0 mm), and an attenuated increase in total peripheral resistance (2.58 +/- 1.2 vs 4.28 +/- 0.9 mmHg/L/min) at -50 mmHg LBNP compared to the C condition. Fluid ingestion (both 20 and 60), partially restored the heart rate, systolic blood pressure, and total peripheral resistance responses to LBNP, but did not influence the change in leg circumference during LBNP (4 +/- 0.3 for R20 and 2.8 +/- 0.4 mm for R60). These data illustrate the effectiveness of fluid ingestion on improving orthostatic responses following exercise, and suggest that dehydration is a contributing factor to orthostatic intolerance following exercise.

Resistance exercise training and the orthostatic response.

Resistance exercise has been suggested to increase blood volume, increase the sensitivity of the carotid baroreceptor cardiac reflex response (BARO), and decrease leg compliance, all factors that are expected to improve orthostatic tolerance. To further test these hypotheses, cardiovascular responses to standing and to pre-syncopal limited lower body negative pressure (LBNP) were measured in two groups of sedentary men before and after a 12-week period of either exercise (n = 10) or no exercise (control, n = 9). Resistance exercise training consisted of nine isotonic exercises, four sets of each, 3 days per week, stressing all major muscle groups. After exercise training, leg muscle volumes increased (P < 0.05) by 4-14%, lean body mass increased (P = 0.00) by 2.0 (0.5) kg, leg compliance and BARO were not significantly altered, and the maximal LBNP tolerated without pre-syncope was not significantly different. Supine resting heart rate was reduced (P = 0.03) without attenuating the heart rate or blood pressure responses during the stand test or LBNP. Also, blood volume (125I and 51Cr) and red cell mass were increased (P < 0.02) by 2.8% and 3.9%, respectively. These findings indicate that intense resistance exercise increases blood volume but does not consistently improve orthostatic tolerance.

Effects of head-down bed rest on complex heart rate variability: response to LBNP testing.

Head-down bed rest is used to model physiological changes during spaceflight. We postulated that bed rest would decrease the degree of complex physiological heart rate variability. We analyzed continuous heart rate data from digitized Holter recordings in eight healthy female volunteers (age 28-34 yr) who underwent a 13-day 6 degree head-down bed rest study with serial lower body negative pressure (LBNP) trials. Heart rate variability was measured on 4-min data sets using conventional time and frequency domain measures as well as with a new measure of signal "complexity" (approximate entropy). Data were obtained pre-bed rest (control), during bed rest (day 4 and day 9 or 11), and 2 days post-bed rest (recovery). Tolerance to LBNP was significantly (P < 0.02) reduced on both bed rest days vs. pre-bed rest. Heart rate variability was assessed at peak LBNP. Heart rate approximate entropy was significantly (P < 0.05) decreased at day 4 and day 9 or 11, returning toward normal during recovery. Heart rate standard deviation and the ratio of high- to low-power frequency did not change significantly. We conclude that short-term bed rest is associated with a decrease in the complex variability of heart rate during LBNP testing in healthy young adult women. Measurement of heart rate complexity, using a method derived from nonlinear dynamics ("chaos theory"), may provide a sensitive marker of this loss of physiological variability, complementing conventional time and frequency domain statistical measures.

Blood volume responses of men and women to bed rest.

This paper reviews a series of studies that indicate that estrogens play an important role in blood volume regulation. The first study illustrates that the plasma volume (PV) of ambulatory women fluctuates during the menstrual cycle, increasing during periods of elevated estrogens. In the second study, it was shown that exogenous and endogenous elevations in blood estrogens attenuate the decrease in PV during bed rest. In the third study, the hypothesis was tested that women, who naturally have a higher blood estrogen content compared with men, will have a smaller loss of PV during bed rest. Ten men and ten women underwent a 13-day, 6 degrees head-down bed rest. Plasma volume and red cell mass (RCM) were measured before and after bed rest using 125I and 51Cr labeling, respectively. Before bed rest, the men and women had similar blood volume (BV) and PV (mL/kg body weight), but the women had a smaller (P < .01) RCM (22.2 +/- 0.9 versus 26.2 +/- 0.8 mL/kg, mean +/- SE). During bed rest, the decrease in RCM (mL/kg) was similar in men and women. However, the decrease in BV was greater in men (8.0 +/- 0.8 mL/kg versus 5.8 +/- 0.8 mL/kg), because of a greater reduction in PV (6.3 +/- 0.6 mL/kg versus 4.1 +/- 0.6 mL/kg). Because the decline in BV has been proposed to contribute to the cardiovascular deconditioning after bed rest, it is possible that women may experience less cardiac and circulatory strain on reambulation.

The effect of dDAVP with saline loading on fluid balance during LBNP and standing after 24-hr head-down bedrest.

Shuttle astronauts currently drink approximately a quart of water with eight salt tablets before reentry to restore lost body fluid and thereby reduce the likelihood of cardiovascular instability and syncope during reentry and after landing. However, the saline loading countermeasure is not entirely effective in restoring orthostatic tolerance to preflight levels. We tested the hypothesis that the effectiveness of this countermeasure could be improved with the use of a vasopressin analog, 1-deamino-8-D-arginine vasopressin (dDAVP). The rationale for this approach is that reducing urine formation with exogenous vasopressin should increase the magnitude and duration of the vascular volume expansion produced by the saline load, and in so doing improve orthostatic tolerance during reentry and postflight.

The effect of blood volume loss on cardiovascular response to lower body negative pressure using a mathematical model.

Different mathematical models of varying complexity have been proposed in recent years to study the cardiovascular (CV) system. However, only a few of them specifically address the response to lower body negative pressure (LBNP), a stress that can be applied in weightlessness to predict changes in orthostatic tolerance. Also, the simulated results produced by these models agree only partially with experimental observations. In contrast, the model proposed by Melchior et al., and modified by Karam et al. is a simple representation of the CV system capable of accurately reproducing observed LBNP responses up to presyncopal levels. There are significant changes in LBNP response due to a loss of blood volume and other alterations that occur in weightlessness and related one-g conditions such as bedrest. A few days of bedrest can cause up to 15% blood volume loss (BVL), with consequent decreases in both stroke volume and cardiac output, and increases in heart rate, mean arterial pressure, and total peripheral resistance. These changes are more pronounced at higher levels of LBNP. This paper presents the results of a simulation study using our CV model to examine the effect of BVL on LBNP response.

Human cardiovascular response to sympathomimetic agents during head-down bed rest: the effect of dietary sodium.

Changes in sympathoadrenal function and cardiovascular deconditioning have long been recognized as a feature of the physiological adaptation to microgravity. The deconditioning process, coupled with altered hydration status, is thought to significantly contribute to orthostatic intolerance upon return to Earth gravity. The cardiovascular response to stimulation by sympathomimetic agents before, during, and after exposure to simulated microgravity was determined in healthy volunteers equilibrated on normal or high sodium diets in order to further the understanding of the deconditioning process.

Occurrence of presyncope in subjects without ventricular innervation.

1. To determine whether activation of the left ventricular C-fibre mechanoreceptors initiates the vasodepressor reflex that often causes syncope, we exposed six orthotopic cardiac transplant patients and six matched, healthy control subjects to progressively increasing lower body negative pressure until the onset of vasodepressor responses. 2. There was no significant difference (P = 0.78) between the central hypovolaemia tolerances of the cardiac transplant and the control groups. 3. The decrease in systolic blood pressure before the onset of vasodepressor reflexes was greater in the cardiac transplant group. The cardiac transplant group did not maintain diastolic blood pressure during central hypovolaemia. From baseline to the onset of vasodepression, there were no differences in leg circumference, forearm blood flow and forearm vascular resistance responses between the two groups. 4. We conclude that the left ventricular mechanoreceptors may not be the primary afferent trigger for syncope.

Transcapillary fluid responses to lower body negative pressure.

The effect of lower body negative pressure (LBNP) on transcapillary fluid balance is unknown. Therefore, our objective was to assess leg interstitial fluid pressures (IFP), leg circumference, plasma volume (PV), and net whole body transcapillary fluid transport (TFT) during and after supine LBNP and to evaluate the addition of oral saline ingestion on transcapillary exchange. Six healthy men 23-41 yr old underwent 4 h of 30 mmHg LBNP, followed by 50 min of supine recovery on two separate occasions, once with and once without ingestion of 1 liter of isotonic saline. IFP was measured continuously in subcutis as well as superficial and deep regions of the tibialis anterior muscle by slit catheters. TFT was calculated by subtracting urine production and calculated insensible fluid loss from changes in PV. During exposure to LBNP, IFP decreased in parallel with chamber pressure, foot venous pressure did not change, leg circumference increased by 3 +/- 0.35% (SE) (P < 0.05), and PV decreased by 14 +/- 2.3%. IFP returned to near control levels after LBNP. At the end of minute 50 of recovery, PV remained decreased (by 7.5 +/- 5.2%) and leg circumference remained elevated (by 1 +/- 0.37%). LBNP alone produced significant movement of fluid into the lower body but no net TFT (-7 +/- 12 ml/h). During LBNP with saline ingestion, 72 +/- 4% of the ingested fluid volume filtered out of the vascular space (TFT = 145 +/- 10 ml/h), and PV decreased by 6 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Orthostatic intolerance during a 13-day bed rest does not result from increased leg compliance.

Increased leg compliance (LC) has been proposed as a mechanism for orthostatic intolerance after spaceflight or bed rest. Using venous occlusion plethysmography with mercury-in-Silastic strain gauge, we evaluated LC before, during, and after a 13-day head-down (-6 degrees) bed rest in 10 men. LC was measured by the relationship between the increased calf areas (in cm2) at thigh cuff occlusions of 20, 30, 50, 70, and 80 mmHg. Orthostatic tolerance was evaluated by a presyncopal-limited lower body negative pressure test (PSL-LBNP) before and after bed rest. The 10 subjects were divided into TOL (n = 5) and INT (n = 5) groups for which the orthostatic tolerance was similar and lower after bed rest, respectively. For TOL (INT) before bed rest, calf area increases were 2.2 +/- 0.5 (SE) (1.3 +/- 0.4), 3.5 +/- 0.7 (2.3 +/- 0.5), 5.0 +/- 0.9 (3.5 +/- 0.6), 5.6 +/- 0.9 (4.4 +/- 0.6), and 6.4 +/- 1.1 (4.7 +/- 0.6) cm2 for thigh occlusion pressures of 20, 30, 50, 70, and 80 mmHg, respectively. Neither for INT nor for TOL were these results significantly changed by bed rest. These results suggest that other mechanisms than increased LC have to be taken into account to explain the decreased orthostatic tolerance induced by this 13-day bed rest.

Simulation of the fluid retention effects of a vasopressin analog using the Guyton model of circulation.

Fluid-loading (FL) consisting of water and salt tablets equivalent of 32 oz of isotonic saline is a countermeasure currently in use by NASA to improve the orthostatic tolerance of astronauts during Shuttle reentry. However, the effectiveness of this countermeasure has been observed to decrease with the duration of space flight. Possible ways to improve fluid retention and thus the effectiveness of FL include use of analogs of vasopressin such as lypressin (LVP). This study used a computer simulation approach to analyze the potential benefits on fluid retention with LVP administered before FL.

Development of lower body negative pressure as a countermeasure for orthostatic intolerance.

Exposure to prolonged (1-4 hr) lower body negative pressure (LBNP) is a countermeasure against postflight orthostatic intolerance which is used in the Soviet space program and planned for use in the American space program. LBNP in combination with fluid-loading is believed to act by promoting a transient positive fluid balance resulting in an increase in vascular, as well as extravascular fluid. Inflight LBNP also may provide beneficial orthostatic effects by restoring baroreceptor reflex functions and/or lower body venous compliance. Current research efforts at the Johnson Space Center are directed towards increasing the effectiveness and efficiency of the LBNP and saline countermeasure. A promising avenue may involve combining pharmacologic agents, such as inhaled anti-diuretic hormone, or mineralocorticoids, with mechanical stimuli such as LBNP.

Sweating and skin blood flow during exercise: effects of age and maximal oxygen uptake.

Individuals greater than or equal to 60 yr of age are more susceptible to hyperthermia than younger people. However, the mechanisms involved remain unclear. To gain further insight, we examined the heat loss responses of 7 young (24-30 yr) and 13 older (58-74 yr) men during 20 min of cycle exercise [67.5% maximal O2 uptake (VO2max)] in a warm environment (30 degrees C, 55% relative humidity). Forearm blood flow (FBF) and chest sweat rate (SR) were plotted as a function of the weighted average of mean skin and esophageal temperatures [Tes(w)] during exercise. The sensitivity and threshold for each response were defined as the slope and Tes(w) at the onset of the response, respectively. When the young sedentary men were compared with a subgroup (n = 7) of the older physically active men with similar VO2max, the SR and FBF responses of the two groups did not differ significantly. However, when the young men were compared with a subgroup of older sedentary men with a similar maximal O2 pulse, the SR and FBF sensitivities were significantly reduced by 62 and 40%, respectively. These findings suggest that during a short exercise bout either 1) there is no primary effect of aging on heat loss responses but, rather, changes are associated with the age-related decrease in VO2max or 2) the decline in heat loss responses due to aging may be masked by repeated exercise training.

Changes in body fluid compartments during a 28-day bed rest.

The extravascular fluid responses to real or simulated space-flight are not well-documented. In this study serial isotope measurements were used to obtain measurements of the body fluid responses of 10 22-29-year-old men during 28 d of simulated microgravity (bed rest). The subjects were maintained on a controlled metabolic diet for 7 d before the study, during 14 d of ambulatory control, 28 d of horizontal bed rest, and 14 d of ambulant recovery. Fluid compartments were measured on control days 1 and 9, bed rest days 2, 14, and 28, and recovery days 7 and 14. By day 2 of bed rest, plasma volume (PV) and extra-cellular volume (ECV) decreased significantly by an average 209 and 533 ml, respectively. Red cell volume (RCV) and total body water (TBW) decreased more slowly, with average losses of 128 and 1,316 ml, respectively, after 28 d of bed rest. Early in the bed rest, TBW loss was mostly from the ECV. Thereafter, the TBW deficit was derived from the intracellular compartment, which decreased an average of 838 ml after 28 d. These results suggest losses from all fluid compartments during bed rest, with no evidence of restoration of ECV after 1-2 weeks.

Repeatability and protocol comparability of presyncopal symptom limited lower body negative pressure exposures.

Data on repeatability and comparability of different presyncopal symptom-limited lower body negative pressure (PSL-LBNP) exposure protocols, while scarce, are critical to the interpretation of studies using PSL-LBNP methods. To investigate if PSL-LBNP tolerance, heart rate, and blood pressure were repeatable, 11 subjects were exposed to 4 PSL-LBNP tests; each test occurring at the same time of day, separated by at least 72 h, and using the same protocol. No significant differences were found in either the heart rate or blood pressure responses to the PSL-LBNP or the tolerance indices (cumulative stress index; maximum negative pressure tolerated; and duration of negative pressure exposure). To study the comparability of different PSL-LBNP protocols, nine subjects were exposed randomly to five PSL-LBNP tests using protocols that varied in stage duration but not pressure profile. The protocols had 1-, 3-, 5-, 7-, or 9-min stage durations. These PSL-LBNP exposures were conducted at the same time of day and separated by at least 72 h. While no differences were noted in either the response pattern or magnitude of heart rate or blood pressure to the differing protocols, the cumulative stress index and the duration of negative pressure exposure varied proportionally with the length of the stage durations. With the exception of the 1-min protocol, the maximum negative pressure tolerated did not vary regardless of the protocol used.(ABSTRACT TRUNCATED AT 250 WORDS)

Automated blood pressure measurements during exercise.

One of the critical parameters measured during exercise is blood pressure. However, the accurate measurement of systolic and diastolic blood pressure during exercise is difficult with auscultation and impractical with direct arterial techniques. The purpose of this study was to compare an automated system (Colin, Inc. STBP-680) with auscultation in humans during rest and exercise and to compare the automated system with direct arterial blood pressure measurement in a canine model during pharmacological challenges that resulted in a wide range of blood pressure values. Compared with direct arterial blood pressure taken in the canine model, the STBP-680 gave good estimates of diastolic blood pressure and adequately monitored relative changes in systolic blood pressure, diastolic blood pressure, and mean arterial pressure (mean arterial pressures in all instances were calculated as one-third systolic plus two-thirds diastolic blood pressures). Compared with auscultation methods in humans, the STBP-680 gave similar estimates of resting diastolic blood pressure and monitored relative changes in resting systolic blood pressures, diastolic blood pressures, and mean arterial pressures. During both treadmill and cycle ergometer exercise in humans, the STBP-680 monitored changes in systolic blood pressure, phase IV diastolic blood pressure, and mean arterial pressure. Further, the STBP-680 estimated exactly and noted relative changes in heart rate in every test. However, during exercise, quantitative estimations of systolic blood pressure by the STBP-680 were higher than those found using auscultation. Where exact, quantitative measures of blood pressure are needed, direct arterial measurement continues to be the most accurate method. However, where indirect methods can be used, the STBP-680 may provide a suitable alternative that reduces many of the technical concerns of auscultation in young, healthy individuals.

Responses to dehydration and rehydration during heat exposure in young and older men.

Body temperature, plasma responses, and subjective ratings of thirst and hotness were studied in 5 older men (OM, 61-67 yr) and 6 younger men (YM, 21-29 yr) during 180-min thermal dehydration and subsequent 60-min rehydration (45 degrees C, 25% relative humidity). Rectal temperature (Tre) increased more rapidly and to a greater magnitude in OM, while average total body sweat rates and chest sweat rates were not significantly different. During dehydration, both OM and YM lost similar body weight (1.52 +/- 0.11 vs. 1.55 +/- 0.22%, mean +/- SE). However, in OM, plasma volume (Pv) decreased (-11.3 +/- 2.8 vs. -4.9 +/- 2.9%), and plasma osmolality (Posm) increased to a greater extent (+5.0 +/- 0.32 vs. 1.1 +/- 0.24 mosmol/kg) compared with YM. On rehydration, OM and YM similarly replaced water debt (46.6 +/- 4.9 vs. 49.0 +/- 3.0%). Within 30 min of drinking, YM had restored Pv and Posm, whereas OM showed slower responses, restoring Posm after 60 min and Pv only after a subsequent 30 min at 25 degrees C. Despite a higher Tre and greater change in Pv and Posm, OM rated themselves less thirsty and not significantly hotter than YM. These findings suggest that aging results in decreased ability to maintain Tre during heat stress and that the mechanisms comprise a combination of alterations in body fluid distribution and perception.