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Biomedical subjects

David A Ludwig

Publications and source records attributed to David A Ludwig.

15 recordsLinked to original sources

R-wave amplitude in lead II of an electrocardiograph correlates with central hypovolemia in human beings.

OBJECTIVES: Previous animal and human experiments have suggested that reduction in central blood volume either increases or decreases the amplitude of R waves in various electrocardiograph (ECG) leads depending on underlying pathophysiology. In this investigation, we used graded central hypovolemia in adult volunteer subjects to test the hypothesis that moderate reductions in central blood volume increases R-wave amplitude in lead II of an ECG. METHODS: A four-lead ECG tracing, heart rate (HR), estimated stroke volume (SV), systolic blood pressure, diastolic blood pressure, and mean arterial pressure were measured during baseline supine rest and during progressive reductions of central blood volume to an estimated volume loss of >1,000 mL with application of lower-body negative pressure (LBNP) in 13 healthy human volunteer subjects. RESULTS: Lower-body negative pressure resulted in a significant progressive reduction in central blood volume, as indicated by a maximal decrease of 65% in SV and maximal elevation of 56% in HR from baseline to -60 mm Hg LBNP. R-wave amplitude increased (p < 0.0001) linearly with progressive LBNP. The amalgamated correlation (R2) between average stroke volume and average R-wave amplitude at each LBNP stage was -0.989. CONCLUSIONS: These results support our hypothesis that reduction of central blood volume in human beings is associated with increased R-wave amplitude in lead II of an ECG.

Adult↗

Heart rate variability and its association with mortality in prehospital trauma patients.

BACKGROUND: Accurate prehospital triage of trauma patients is difficult, especially in mass casualty situations. Accordingly, the U.S. Military has initiated a program directed toward improving noninvasive prehospital triage algorithms based on available physiologic data. The purpose of this study was to assess heart rate variability and its association with mortality in prehospital trauma patients. METHODS: Trauma patients without significant head injury requiring helicopter transport were identified from a retrospective research database. An equal number, unmatched sample of patients who lived were compared with those who died (n = 15 per group). All patients were transported to a single Level I urban trauma center. The primary independent variable was mortality. Patients with Abbreviated Injury Scale head scores >2 were excluded from the analysis, so that the effects seen were based on hemorrhagic shock. Age, sex, Glasgow Coma Scale score (GCS), blood pressure, pulse pressure, pulse, intubation rate, SpO2, mechanism of injury, transport time, and time of death after admission were recorded. R-waves from the first available 120 seconds of usable data were detected from normal electrocardiograms and heart rate variability was assessed. RESULTS: Patients who died demonstrated a lower GCS (7.9 +/- 1.4 versus 14.4 +/- 0.2; p = 0.0001) and higher intubation rate (53% of patients who died versus 0% patients who lived). Pulse rate, arterial pressure, and SpO2 were not distinguishable statistically between groups (p = 0.08), but pulse pressure was lower in patients who died (39 +/- 3 versus 50 +/- 2 mm Hg; p = 0.01). Compared with patients who lived, those who died had lower normalized low-frequency (LF) power (42 +/- 6 versus 62 +/- 4 LFnu; p = 0.009), higher high-frequency (HF) power (42 +/- 3 versus 32 +/- 3 HFnu; p = 0.04) and higher HF-to-LF ratio (144 +/- 30 versus 62 +/- 11nu; p = 0.01). With absolute HF/LF adjusted for GCS, the intergroup variance accounted for by HF/LF was reduced to 6% (p = 0.16). CONCLUSIONS: Analysis of heart rate variability provides insight into adequacy of autonomic compensation to severe trauma. In our cohort of trauma patients, low pulse pressures coupled with relatively higher parasympathetic than sympathetic modulation characterized and separated patients who died versus patients who survived traumatic injuries when standard physiologic measurements are not different. These data do not suggest advantages of heart rate variability analysis over GCS scores, but suggest future possibilities for remote noninvasive triage of casualties when GCS scores are unattainable.

Abbreviated Injury Scale↗

Association of ambulatory blood pressure and dietary caffeine in adolescents.

BACKGROUND: Although relatively little is known about the responsible factors, there is an increased prevalence of essential hypertension in youth. Our previous research using casual blood pressure (BP) suggests a role for caffeine intake. The objective of this study was to assess the association between caffeine intake and ambulatory BP patterns among adolescents and to replicate our previous findings that compared caffeine intake to BP values obtained at a single time point. METHODS: Eighty-two African-American and non-Hispanic white adolescents (15 to 19 years old) with normal systolic BP selected foods and beverages for a 4-day sodium-controlled diet. Subjects were stratified into three groups based on the amount of caffeine in these foods. Ambulatory BP measures (24-h) were recorded during 1 day of the 4-day diet. The effects of ethnicity, caffeine, and the interaction of ethnicity and caffeine on BP were assessed for daytime and nighttime hours controlling for gender and body mass index. RESULTS: The level of dietary caffeine was positively associated with daytime systolic BP (F(2,76) = 3.1, P = .05, partial R(2) = 0.07) and daytime diastolic BP (F = 3.53(2,76), P = .03, partial R(2) = 0.07). Caffeine's effect on systolic BP was most pronounced for African-American subjects. These results replicated our earlier findings. There was no association between caffeine intake and nighttime BP. CONCLUSIONS: This investigation replicates and extends our previous findings that caffeine consumption impacts the BP of adolescents, during the daytime when sympathetic nervous system responses dominate BP control. Controlled studies that examine the pressor effects of caffeine intake at levels typical of the dietary patterns of today's adolescents are needed.

Adolescent↗

African-American adolescents' stress responses after the 9/11/01 terrorist attacks.

PURPOSE: To examine the impact of indirect exposure to the 9/11/01 attacks upon physical and emotional stress-related responses in a community sample of African-American (AA) adolescents. METHODS: Three months after the 9/11/01 terrorist attacks, 406 AA adolescents (mean age [SD] of 16.1 +/- 1.3 years) from an inner-city high school in Augusta, GA were evaluated with a 12-item 5-point Likert scale measuring loss of psychosocial resources (PRS) such as control, hope, optimism, and perceived support, a 17-item 5-point Likert scale measuring post-traumatic stress symptomatology (PCL), and measures of state and trait anger, anger expression, and hostility. Given the observational nature of the study, statistical differences and correlations were evaluated for effect size before statistical testing (5% minimum variance explained). Bootstrapping was used for testing mean differences and differences between correlations. RESULTS: PCL scores indicated that approximately 10% of the sample was experiencing probable clinically significant levels of post-traumatic distress (PCL score > 50). The PCL and PRS were moderately correlated with a r = .59. Gender differences for the PCL and PRS were small, accounting for 1% of the total variance. Higher PCL scores were associated with higher state anger (r = .47), as well as measures of anger-out (r = .32) and trait anger (r = .34). Higher PRS scores were associated only with higher state anger (r = .27). Scores on the two 9/11/01-related scales were not statistically associated (i.e., less than 5% of the variance explained) with traits of anger control, anger-in, or hostility. CONCLUSIONS: The majority of students were not overly stressed by indirect exposure to the events of 9/11/01, perhaps owing to the temporal, social, and/or geographical distance from the event. Those who reported greater negative impact appeared to also be experiencing higher levels of current anger and exhibited a characterologic style of higher overt anger expression.

Adolescent↗

Use and misuse of p-values in designed and observational studies: guide for researchers and reviewers.

Analysis of scientific data involves many components, one of which is often statistical testing with the calculation of p-values. However, researchers too often pepper their papers with p-values in the absence of critical thinking about their results. In fact, statistical tests in their various forms address just one question: does an observed difference exceed that which might reasonably be expected solely as a result of sampling error and/or random allocation of experimental material? Such tests are best applied to the results of designed studies with reasonable control of experimental error and sampling error, as well as acquisition of a sufficient sample size. Nevertheless, attributing an observed difference to a specific treatment effect requires critical thinking on the part of the scientist. Observational studies involve data sets whose size is usually a matter of convenience with results that reflect a number of potentially confounding factors. In this situation, statistical testing is not appropriate and p-values may be misleading; other more modern statistical tools should be used instead, including graphic analysis, computer-intensive methods, regression trees, and other procedures broadly classified as bioinformatics, data mining, and exploratory data analysis. In this review, the utility of p-values calculated from designed experiments and observational studies are discussed, leading to the formation of a decision tree to aid researchers and reviewers in understanding both the benefits and limitations of statistical testing.

Clinical Trials as Topic↗

Stroke volume and sympathetic responses to lower-body negative pressure reveal new insight into circulatory shock in humans.

We measured various hemodynamic responses and muscle sympathetic nerve activity (MSNA) in human subjects during a graded lower-body negative pressure (LBNP) protocol to test the hypotheses that: (1) reduced stroke volume (SV) is linearly related to increased MSNA; and (2) the onset of symptoms of impending cardiovascular collapse is associated with hypoadrenergic responses to central hypovolemia. We measured heart rates, arterial blood pressures, sympathetic neural activity (MSNA; peroneal nerve microneurography), and relative changes (% Delta) in SV (thoracic electrical bioimpedance) in 13 men during exposure to graded levels of LBNP. After a 12-min baseline data collection period, LBNP was initiated at -15 mm Hg for 12 min followed by continuous stepwise increments to -30, -45, and -60 mm Hg for 12 min each. Eight subjects completed the LBNP protocol (finishers), while the protocol was terminated prematurely during -60 mm Hg in five subjects due to onset of symptoms of cardiovascular collapse (nonfinishers). Of these subjects, we were able to record MSNA successfully throughout the LBNP protocol in four finishers and two nonfinishers. The relationship between average change in stroke volume and average change in MSNA was linear (% DeltaMSNA=464-3.6 [% DeltaSV], r2=0.98). On average, MSNA was greater in the nonfinishers at each level of LBNP compared to finishers, but peripheral resistance was lower. Our results support the hypothesis that MSNA activation is inversely related and linear to stroke volume reductions during central hypovolemia. Sympathetic withdrawal rather than hypoadrenergic function may represent a fundamental mechanism for the development of circulatory shock.

Adult↗

The association of caffeinated beverages with blood pressure in adolescents.

OBJECTIVE: To assess the association between the consumption of caffeinated beverages and blood pressure in African American and white adolescents. DESIGN: This study was part of ongoing research examining stress-induced hemodynamic responses in adolescents. African American and white adolescents (n = 159) selected foods and beverages for a 3-day sodium-controlled diet. Caffeine in these foods was used to stratify participants into 3 categories (0-50 mg/d, >50-100 mg/d, and >100 mg/d). Before menu selection, blood pressure readings were obtained. STATISTICAL ANALYSIS: A general linear model (multiple regression with both categorical and continuous variables) was developed to assess the effects of race, category of caffeine intake, and interaction of race and caffeine intake on systolic and diastolic blood pressure controlling for sex and body mass index (calculated as weight in kilograms divided by height in meters squared). RESULTS: The association between systolic blood pressure and caffeine category varied by race (P =.001). African Americans consuming more than 100 mg/d of caffeine had higher systolic blood pressure readings than the groups consuming 0 to 50 mg/d (mean difference, 6.0 mm Hg; 95% confidence interval [CI], 2.3 to 9.7) or more than 50 to 100 mg/d (mean difference, 7.1 mm Hg; 95% CI, 3.4 to 10.7). The effect on diastolic blood pressure was less pronounced (P =.08). The diastolic blood pressure of the group consuming more than 100 mg/d was 3.7 mm Hg (95% CI, 0.41 to 7.0) higher than the group consuming more than 50 to 100 mg/d and was not statistically different from the group consuming 0 to 50 mg/d (mean difference, 2.4 mm Hg; 95% CI, -0.9 to 5.8). There was no evidence that the association between diastolic blood pressure and caffeine intake varied by race (P =.80). CONCLUSIONS: For adolescents, especially African American adolescents, caffeine intake may increase blood pressure and thereby increase the risk of hypertension. Alternatively, caffeinated drink consumption may be a marker for dietary and lifestyle practices that together influence blood pressure. Additional research is needed owing to rising rates of adolescent hypertension and soft drink consumption.

Adolescent↗

Effects of inspiratory impedance on the carotid-cardiac baroreflex response in humans.

We were interested in a therapeutic device designed to increase carotid-cardiac baroreflex sensitivity (BRS) since high BRS is associated with a lower risk for development of hypotension in humans with experimentally-induced central hypovolemia. We hypothesized that spontaneous breathing through an impedance threshold device (ITD) designed to increase negative intrathoracic pressure during inspiration and elevate arterial blood pressure would acutely increase BRS in humans. We tested this hypothesis by measuring heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures, and carotid-cardiac BRS in 10 female and 10 male subjects breathing through a face mask at three separate ITD conditions: (a) 6 cm H(2)O; (b) 12 cm H(2)O; and (c) a control (0 cm H(2)O). HR was increased (P = 0. 013) from 64 +/- 3 bpm during control to 68 +/- 3 bpm at 6 cm H(2)O ITD and 71 +/- 4 bpm at 12 cm H(2)O ITD breathing conditions. During ITD breathing, BRS was not altered but responses were shifted to higher arterial pressures. However, SBP and DBP were elevated for both the 6 and 12 cm H(2)O conditions compared to the 0 cm H(2)O condition, but returned to control (sham) levels by 30 minutes after cessation of ITD breathing. There were no gender effects for BRS or any hemodynamic responses to breathing through the ITD. We conclude that breathing with inspiratory impedance at relatively low pressures can increase baseline arterial blood pressure, i. e., reset the operational point for SBP on the baroreflex stimulus-response relationship, in healthy subjects. This resetting of the cardiac baroreflex may represent a mechanism that allows blood pressure to increase without a reflex-mediated reduction in HR.

Adult↗

Food habits are related to glycemic control among people with type 2 diabetes mellitus.

OBJECTIVE: To investigate the food habits of people with type 2 diabetes and to identify those habits related to glycemic control. DESIGN: The purposive sampling plan targeted people (40 to 65 years old) living in two urban communities in the Southeastern United States with type 2 diabetes for >1 year (60% women, 50% African Americans and low-income individuals). In-depth interviews were used to identify food habits. Glycated hemoglobin (HbA(1c)) was measured to assess glycemic control. SUBJECTS: The final sample contained 89 participants (62% women, 48% African American, and 43% below 200% of the poverty level). STATISTICAL ANALYSES PERFORMED: Analysis of variance, principal component/factor analysis, cluster analysis, and multiple regression were used to relate food habits to glycemic control. RESULTS: A four-factor solution derived from 15 food habits explained 51.5% of the total variance in HbA(1c) values. High factor scores for three factors (Basic Eating Practices, Meal Planning, and Carbohydrate/Vegetable Strategies) and low factor scores for a fourth factor (Challenges of Dining Out) were related to lower HbA(1c) values. Based on similar patterns across the 15 food habits, participants were clustered into four groupings. The clusters differing on HbA(1c) (mean+/-standard deviation) were Healthful Eating Lifestyle (6.25+/-0.25), Disciplined Eating Approach (7.31+/-0.35), Limited Dietary Focus (8.28+/-0.33), and Poor Dietary Management (9.05+/-0.24). These groupings reflected different food habit factor profiles. CONCLUSIONS: Knowledge of the specific food habits of people with diabetes can offer a way to structure a meaningful dialog with clients about dietary self-management and guide the collaborative development of relevant dietary goals.

Adult↗

Gender influences endothelial-dependent arterial dilatation via arterial size in youth.

BACKGROUND: Reduced endothelial-dependent arterial dilatation (EDAD) has been suggested as an early marker of arteriosclerosis, since it has been reported to correlate with known cardiovascular disease (CVD) risk factors. It is unclear, however, whether gender plays a mediating or a moderating role in these relationships. The aim of this study was to evaluate the influence of gender on EDAD in youth at risk for CVD. METHODS: The sample population of 261 individuals (mean age, 20 yr; SD, 3 yr) consisted of 148 African Americans, 113 European Americans, 133 males, and 128 females, all with a verified family history of CVD (ie, hypertension, myocardial infarction). Anthropometrics, sociometrics, hemodynamics, brachial artery diameter, left ventricular mass, and relative wall thickness were measured and used as independent variables. EDAD (dependent variable) was expressed as percent (%) change of brachial artery diameter to reactive hyperemia induced by pressure cuff occlusion and release. Artery diameters were calculated via an automated border detection system. RESULTS: Percent EDAD change was inversely related to initial diameter of the brachial artery. Mean percent EDAD change was 14.37% for female subjects compared with 10.48% for male subjects. The gender difference was a function of smaller initial artery size in the female subjects. When initial diameter and gender were considered simultaneously within a multivariate model, the gender effect was eliminated. Although a large prediameter effect remained, the relationship between prediameter and EDAD was greater in female than in male subjects (ie, interaction/moderating effect). CONCLUSION: The data suggest that the smaller the artery is, the more it will dilate. Further EDAD investigations are needed to predict arteriosclerosis, taking into account of the gender difference in vessel size.

Adolescent↗

Hemodynamics associated with breathing through an inspiratory impedance threshold device in human volunteers.

OBJECTIVE: Increased negative intrathoracic pressure during spontaneous inspiration through an impedance threshold device (ITD) causes elevated arterial blood pressure in humans. This study was performed to determine whether the acute increase in blood pressure induced by breathing through an ITD is associated with increased stroke volume and cardiac output. DESIGN: Randomized, blinded, controlled trial. SETTING: Laboratory. SUBJECTS: Ten women and ten men. INTERVENTIONS: We measured hemodynamic and respiratory responses during two separate ITD conditions: 1) breathing through a face mask with an ITD (impedance of 6 cm H2O [0.59 kPa]) and 2) breathing through the same face mask with a sham ITD (control). Stroke volume was measured by thoracic bioimpedance. MEASUREMENTS AND MAIN RESULTS: Compared with the control condition, ITD produced higher stroke volume (124 +/- 3 vs. 137 +/- 3 mL; p = .013), heart rate (63 +/- 3 vs. 68 +/- 3 beats/min; p = .049), cardiac output (7.69 vs. 9.34 L/min; p = .001), and systolic blood pressure (115 +/- 2 to 122 +/- 2 mm Hg [15.33 +/- 0.3 to 16.26 +/- 0.3 kPa]; p = .005) without affecting expired minute ventilation (6.2 +/- 0.4 to 6.5 +/- 0.4 L/min; p = .609). CONCLUSIONS: Breathing with an ITD at relatively low impedance increases systolic blood pressure by increasing stroke volume and cardiac output. The ITD may provide short-term protection against cardiovascular collapse induced by orthostatic stress or hemorrhage.

Adult↗

Bed rest affects ventricular and arterial elastances in monkeys: implications for humans.

METHODS: Experimental data were obtained from five chronically instrumented rhesus monkeys exposed to 96 h of 10 degrees head-down bed rest (HDBR) and another 96 h of 80 degrees upright control separated by 9 d of ambulatory recovery in a counter-balanced, crossover experiment design to test the hypotheses that: 1) headward and footward fluid shifts would increase systemic arterial (Eart) and left ventricular end-systolic (Ees) elastances; and 2) changes in Eart and Ees would be related in magnitude and direction. Ees and Eart were calculated from measurements taken during five observation periods for initial 2-h and 4-d exposures to HDBR that produced headward volume shifts, and acute exposure to graded levels of lower body negative pressure (LBNP) designed to produce orthostatic volume shifts. RESULTS: There was no effect of HDBR on Ees and Eart for any observation period (initial 2-h, 4-d, or LBNP). Eart increased in a similar pattern during the 4-d exposure to both control and HDBR. Ees increased with increasing LBNP levels for both control and HDBR while Eart remained unchanged. CONCLUSION: Our data are consistent with the notion that elevated Eart may represent an adaptation to physical inactivity that is associated with cardiovascular deconditioning.

Adaptation, Physiological↗

Effects of repeated Valsalva maneuver straining on cardiac and vasoconstrictive baroreflex responses.

INTRODUCTION: We hypothesized that repeated respiratory straining maneuvers (repeated SM) designed to elevate arterial BPs (arterial baroreceptor loading) would acutely increase baroreflex responses. METHODS: We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures), and changes in heart rate and diastolic BP after reductions in BP induced by a 15-s Valsalva maneuver in 10 female and 10 male subjects at 1, 3, 6, and 24 h after performing repeated SM. Baroreflex responses were also measured in each subject at 1, 3, 6, and 24 h at the same time on a separate day without repeated SM (control) in a randomized, counter-balanced cross-over experimental design. RESULTS: There was no statistical difference in carotid-cardiac and peripheral vascular baroreflex responses measured across time following repeated SM compared with the control condition. Integrated cardiac baroreflex response (deltaHR/ deltaSBP) measured during performance of a Valsalva maneuver was increased by approximately 50% to 1.1 +/- 0.2 bpm x mm Hg(-1) at 1 h and 1.0 +/- 0.1 bpm x mm Hg(-1) at 3 h following repeated SM compared with the control condition (0.7 +/- 0.1 bpm x mm Hg(-1) at both 1 and 3 h, respectively). However, integrated cardiac baroreflex response after repeated SM returned to control levels at 6 and 24 h after training. These responses did not differ between men and women. CONCLUSIONS: Our results are consistent with the notion that arterial baroreceptor loading induced by repeated SM increased aortic, but not carotid, cardiac baroreflex responses for as long as 3 h after repeated SM. We conclude that repeated SM increases cardiac baroreflex responsiveness which may provide patients, astronauts, and high-performance aircraft pilots with protection from development of orthostatic hypotension.

Adult↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗