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.

Managed care in the public sector: lessons learned from the Los Angeles PARTNERS program.

PARTNERS is the Los Angeles County Department of Mental Health's capitated managed care treatment program. To explore the context in which public sector managed care reforms are occurring and to understand the obstacles to implementing such programs, qualitative data were collected from administrators, case managers, and clients. Administrators were found to need assistance in negotiating managed care contracts and in tracking costs. Case managers, although concerned about increased clinical demands, enjoyed the flexibility and creativity their new roles allowed. Clients were satisfied with their increased independence, even though many had to change their site of care. Beyond considering these concerns, the range of community stakeholders who may be affected by such interventions must be addressed.

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.

Simultaneous cerebrovascular and cardiovascular responses during presyncope.

BACKGROUND AND PURPOSE: Presyncope, characterized by symptoms and signs indicative of imminent syncope, can be aborted in many situations before loss of consciousness occurs. The plasticity of cerebral autoregulation in healthy humans and its behavior during this syncopal prodrome are unclear, although systemic hemodynamic instability has been suggested as a key factor in the precipitation of syncope. Using lower body negative pressure (LBNP) to simulate central hypovolemia, we previously observed falling mean flow velocities (MFVs) with maintained mean arterial blood pressure (MABP). These findings, and recent reports suggesting increased vascular tone within the cerebral vasculature at presyncope, cannot be explained by the classic static cerebral autoregulation curve; neither can they be totally explained by a recent suggestion of a rightward shift in this curve. METHODS: Four male and five female healthy volunteers were exposed to presyncopal LBNP to evaluate their cerebrovascular and cardiovascular responses by use of continuous acquisition of MFV from the right middle cerebral artery with transcranial Doppler sonography, MABP (Finapres), and heart rate (ECG). RESULTS: At presyncope, MFV dropped on average by 27.3 +/- 14% of its baseline value (P < .05), while MABP remained at 2.0 +/- 27% above its baseline level. Estimated cerebrovascular resistance increased during LBNP. The percentage change from baseline to presyncope in MFV and MABP revealed consistent decreases in MFV before MABP. CONCLUSIONS: Increased estimated cerebrovascular resistance, falling MFV, and constant MABP are evidence of an increase in cerebral vascular tone with falling flow, suggesting a downward shift in the cerebral autoregulation curve. Cerebral vessels may have a differential sensitivity to sympathetic drive or more than one type of sympathetic innervation. Future work to induce dynamic changes in MABP during LBNP may help in assessing the plasticity of the cerebral autoregulation mechanism.

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.

Cardiovascular responses to exhaustive upright cycle exercise in highly trained older men.

It is unclear whether the markedly enhanced aerobic exercise capacity of older endurance-trained men relative to their sedentary age peers is mediated primarily by central or peripheral cardiovascular mechanisms. To address this question, we performed radionuclide ventriculography with respiratory gas exchange measurements during exhaustive upright cycle ergometry in 16 endurance-trained men aged 63 +/- 7 yr and in 35 untrained men of similar age. As expected, maximal O2 consumption during treadmill exercise was much higher in athletes than in controls. At rest and during fixed submaximal cycle work rates through 100 W, athletes demonstrated lower heart rates and greater stroke volume indexes than controls while maintaining similar cardiac indexes and O2 uptake (VO2). At exhaustion, athletes achieved 53% higher work rates and peak VO2 per kilogram body weight than the sedentary men. The higher peak VO2 in athletes was achieved by a 22.5% larger cardiac index and a 15.6% greater arteriovenous O2 difference. The larger peak cardiac index in the athletes than in sedentary controls was mediated entirely by a greater stroke volume index; peak heart rates were virtually identical. The athletes' greater stroke volume index was achieved through an 11% larger end-diastolic volume index and a 7% higher ejection fraction, both of borderline significance. At exhaustion, athletes demonstrated a lower systemic vascular resistance than controls, despite a higher value at rest. Athletes also showed greater exercise-induced increments in heart rate, stroke volume index, and cardiac index and a greater reduction in systemic vascular resistance from rest to maximal workload.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of lower body negative pressure to assess changes in heart rate response to orthostatic-like stress during 17 weeks of bed rest.

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

Cardiovascular responses to standing: effect of hydration.

Many astronauts experience intolerance to orthostatic stress after space flight, despite the ingestion of salt tablets and water equivalent to 0.9% saline just before their return to Earth. Previous research indicates that the ingestion of 1.07% saline solution increased plasma volume more than did 0.9% saline. Therefore, the authors hypothesized that the 1.07% saline would be more effective in reducing orthostatic stress during standing. In this study, six men (22-47 years) performed a 5-minute "stand test" (5 minutes supine followed by 5 minutes standing) under four hydration conditions: 1) hypohydrated (HYPO, 20 mg intravenous [IV] Lasix), 2) euhydrated (EU), 3) rehydrated with 1 L 0.9% saline 2 hours after Lasix, or 4) rehydrated with 1 L 1.07% saline. Stand tests were done 4 5 hours after rehydration. Plasma volume was reduced 10% after Lasix, and was restored by both rehydration solutions. When subjects stood, their diastolic pressure, mean pressure, heart rate (HR), and peripheral resistance increased (P < .05), and their stroke volume (SV), cardiac output (CO), and thoracic fluid (TF, by impedance cardiography) decreased (P < .05). Systolic arterial pressure (SBP) increased when subjects stood after saline, but decreased if subjects were HYPO or EU (P < .05 for 1.07% versus HYPO and EU). Heart rate (HR), another indicator of orthostatic stress, did not differ among hydration states. During the last minute of the stand test, TF was greater if subjects had fluid countermeasures. Stroke volume, CO, and TF were significantly less during minute 5 of standing than during minute 3. Whether they would continue to fall in a longer stand test is not known. The results for SBP indicate that 1.07% saline may have advantages over 0.9% saline as a countermeasure to postspace-flight or postbedrest orthostatic intolerance.

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.

Cardiovascular responses to lower body negative pressure in trained and untrained older men.

To determine whether aerobic conditioning alters the orthostatic responses of older subjects, cardiovascular performance was monitored during graded lower body negative pressure in nine highly trained male senior athletes (A) aged 59-73 yr [maximum O2 uptake (VO2 max) = 52.4 +/- 1.7 ml.kg-1 x min-1] and nine age-matched control subjects (C) (VO2 max = 31.0 +/- 2.9 ml.kg-1 x min-1). Cardiac volumes were determined from gated blood pool scintigrams by use of 99mTc-labeled erythrocytes. During lower body negative pressure (0 to -50 mmHg), left ventricular end-diastolic and end-systolic volume indexes and stroke volume index decreased in both groups while heart rate increased. The decreases in cardiac volumes and mean arterial pressure and the increase in heart rate between 0 and -50 mmHg were significantly less in A than in C. For example, end-diastolic volume index decreased by 32 +/- 4 ml in C vs. 14 +/- 2 ml in A (P < 0.01), mean arterial pressure declined 7 +/- 5 mmHg in C and increased by 5 +/- 3 mmHg in A (P < 0.05), and heart rate increased 13 +/- 3 beats/min in C and 7 +/- 1 beats/min in A (P < 0.05). These data suggest that increased VO2 max among older men is associated with improved orthostatic responses.