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Purpose: To assess the effects of manipulating the loading of successive sets of midthigh clean pulls on the potentiation capabilities of 7 international-level US weightlifters (4 men, 3 women). Methods: Isometric and dynamic peak-force characteristics were measured with a force plate at 500 Hz. Velocity during dynamic pulls was measured using 2 potentiometers that were suspended from the top of the right and left sides of the testing system and attached to both ends of the bar. Five dynamic-performance trials were used (in the following order) as the potentiation protocol: women at 60, 80, 100, 120, and 80 kg and men at 60, 140, 180, 220, and 140 kg. Trials 2 vs 5 were specifically analyzed to assess potentiation capabilities. Isometric midthigh pulls were assessed for peak force and rate of force development. Dynamic lifts were assessed for peak force (PF), peak velocity (PV), peak power (PP), and rate of force development (RFD). Results: Although all values (PF, PV, PP, and RFD) were higher postpotentiation, the only statistically higher value was found for PV (ICCα = .95, P = .011, η2 = .69). Conclusions: Results suggest that manipulating set-loading configuration can result in a potentiation effect when heavily loaded sets are followed by a lighter set. This potentiation effect was primarily characterized by an increase in the PV in elite weightlifters. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to study the effects of an 11-week training period performed by female weightlifters. Two weeks before this investigation, baseline measures for total testosterone, cortisol, and testosterone:cortisol ratio were collected. The 11-week training program consisted of the core exercises (i.e., clean, clean and jerk, and snatch) and other supplemental exercises (i.e., clean pull, snatch pull, squat, and front squat). Hormonal, isometric, and dynamic middle thigh pull force-time curve characteristics were assessed biweekly throughout the duration of the investigation, whereas volume load and training intensity were assessed weekly throughout the investigation. The testosterone:cortisol ratio of the baseline (1.19 +/- 0.64) was significantly different from the ratio of weeks 1 (0.67 +/- 0.36) and 9 (0.94 +/- 0.66). When the week-to-week values were compared, week 1 (0.67 +/- 0.36) was significantly different (P < 0.05; eta = 0.84) from week 3 (1.06 +/- 0.54). A very strong correlation (r = -0.83; r = 0.69) was found between the percentage change of the testosterone:cortisol ratio and volume load from weeks 1 to 11. Moderate to very strong correlations were noted between the percentage change in volume load and isometric peak force, peak force during the 30% isometric peak force trial, and peak force during the 100-kg trial during the 11 weeks of training. The primary finding of this study was that alterations in training volume load can result in concomitant changes in the anabolic-to-catabolic balance, as indicated by the testosterone:cortisol ratio, and the ability to generate maximal forces. [ABSTRACT FROM AUTHOR]

Stretching is commonly used by many athletes in different sports. Although acute stretching, as part of a warm-up, can enhance range of motion, it may also reduce performance. Acute stretching can reduce peak force, rate of force production, and power output. Chronic stretching may enhance performance, although the mechanism is unclear. Acute stretching has little effect on injury. However, chronic stretching (not part of warm-up) may have some injury reduction potential. [ABSTRACT FROM AUTHOR]

Abstract: Stone, MH, Hornsby, G, Mizuguchi, S, Sato, K, Gahreman, D, Duca, M, Carroll, K, Ramsey, MW, Stone, ME, and Haff, GG. The use of free weight squats in sports: a narrative review-squatting movements, adaptation, and sports performance: physiological. J Strength Cond Res 38(8): 1494-1508, 2024-The squat and its variants can provide numerous benefits including positively affecting sports performance and injury prevention, injury severity reduction, and rehabilitation. The positive benefits of squat are likely the result of training-induced neural alterations and mechanical and morphological adaptations in tendons, skeletal muscles, and bones, resulting in increased tissue stiffness and cross-sectional area (CSA). Although direct evidence is lacking, structural adaptations can also be expected to occur in ligaments. These adaptations are thought to beneficially increase force transmission and mechanical resistance (e.g., resistance to mechanical strain) and reduce the likelihood and severity of injuries. Adaptations such as these, also likely play an important role in rehabilitation, particularly for injuries that require restricted use or immobilization of body parts and thus lead to a consequential reduction in the CSA and alterations in the mechanical properties of tendons, skeletal muscles, and ligaments. Both volume and particularly intensity (e.g., levels of loading used) of training seem to be important for the mechanical and morphological adaptations for at least skeletal muscles, tendons, and bones. Therefore, the training intensity and volume used for the squat and its variations should progressively become greater while adhering to the concept of periodization and recognized training principles., (Copyright © 2024 National Strength and Conditioning Association.)

Abstract: Lang, HM, Duffourc, MM, Bazyler, CD, Ramsey, MW, and Gentles, JA. The relationship between cell-free DNA and resistance training volume load. J Strength Cond Res 38(6): 1008-1012, 2024-The primary purpose of this study was to assess the sensitivity of cell-free DNA (cf-DNA) to different resistance training volume loads. The secondary purpose was to examine the relationship between change in cf-DNA and relative strength. Researchers hypothesized that (a) cf-DNA concentrations would increase with increasing volume load and (b) increases in relative strength would result in predicted decreases to %Δ of cf-DNA. Thirty subjects were recruited for this study, 15 men and 15 women. Blood was collected through venous draws into 4-ml vacutainers at 3 time points: immediately before (T1), after 3 sets (T2), and after 6 sets (T3) of the back squat exercise. A critical alpha of 0.05 was set for inferential statistics. A repeated-measures ANOVA showed that cf-DNA increased significantly from T1 (407.72 ± 320.83) to T2 (1,244.6 ± 875.83) ( p < 0.01) and T1 (407.72 ± 320.83) to T3 (1,331.15 ± 1,141.66) ( p < 0.01), whereas no difference was found from T2 to T3 ( p = 1.00). The linear regression model used to examine the predictive capabilities relative strength had on cf-DNA %Δ from T1 to T3 was found to be significant ( p = 0.04; R2 = 0.15). The results of this study demonstrate the short response of cf-DNA in relation to variations in resistance training volume load. Results also demonstrated the positive relationship between relative strength and cf-DNA %Δ. The current study builds on the body of research that cf-DNA provides insight regarding the level of immune response after exercise training., (Copyright © 2024 National Strength and Conditioning Association.)

Solid tumors contain hypoxic regions that contribute to anticancer therapy resistance. Thus, mitigating tumor hypoxia may enhance the efficacy of radiation therapy which is commonly utilized for patients with prostate cancer. Increasing perfusion pressure in the prostate with head-up tilt (HUT) may augment prostate tumor perfusion and decrease hypoxia. The purpose of this study was to determine if an increase in the vascular hydrostatic gradient via 70° HUT increases tumor perfusion and decreases tumor hypoxia in a preclinical orthotopic model of prostate cancer. Male Copenhagen rats (n = 17) were orthotopically injected with Dunning R-3327 (AT-1) prostate adenocarcinoma cells to induce prostate tumors. After tumors were established, prostate tumor perfusion and hypoxia were measured in rats during level (0°) and 70° HUT positions. To compare the magnitude of the hydrostatic column to that present in humans, ultrasound was used to measure the heart to prostate distance in male human subjects to estimate the prostate vascular hydrostatic pressure with the upright posture. In young rats, no differences were detected in prostate tumor perfusion or prostate tumor hypoxia with 70° HUT versus the level position. However, from the retrospective study, young rats increased prostate vascular resistance to HUT, whereas aged rats lacked this response. Tumor vessels co-opted from existing functional vasculature in young rats may be sufficient to negate increases in perfusion pressure with HUT seen in aged rats. Additionally, in humans, the estimated hydrostatic column at the level of the prostate is five times greater than that of the rat. Therefore, 70° HUT may elicit increases in prostate/prostate tumor blood flow in humans that is not seen in rats., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: To understand African Americans' perceptions, barriers, and facilitators to recruitment, enrollment, adoption, maintenance, and retention in a nutrition and physical activity promotion program., Design: Four focus groups were conducted., Setting: Two community settings located in Jackson and Hattiesburg, Mississippi., Participants: Participants (n = 28) were aged 18-50 years., Main Outcome Measure(s): Barriers and facilitators associated with healthy eating, physical activity, achieving a healthy weight, and participation in a health behavior change program., Analysis: A conventional thematic content analysis approach includes data familiarization, initial code generation, initial theme generation, themes review, and team review for finalization of themes., Results: Major themes related to health behaviors and participation in a behavior change program were identified by participants, including time constraints, costs, social support, consistency and self-efficacy, motivation for longevity and disease prevention, physical appearance, fear of injury/pain, social norms/stigma associated with outdoor physical activity, body criticism from family members, and having empathic and validating program staff support., Conclusions and Implications: Several social determinants of health were identified as essential considerations for promoting healthy nutrition and physical activity behaviors among African American adult Mississippians. Cultural and spiritual implications were also identified. Study insights inform policy approaches for designing culturally appropriate health behavior change programs in the Deep South., (Copyright © 2022 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Purpose: Little is known about racial/ethnic minority substance use and disorder-related disparities among sexual minorities as compared to their heterosexual counterparts. This study aimed to understand the associations between sexual minority status and substance use and disorders among U.S. adults stratified by race/ethnicity. Methods : We analyzed data from a sample of U.S. adults ( n  = 35,981) surveyed during the 2012-2013 National Epidemiological Survey on Alcohol and Related Conditions-III. Respondents were categorized into four sexual minority statuses: heterosexual, gay/lesbian, bisexual, and conflicting. Respondents' substance (tobacco, alcohol, and marijuana) use and disorders were also assessed using standard measures. Weighted multivariable logistic regressions were used to examine the relationships between sexual minority status and substance use and disorders, stratified by race/ethnicity, adjusting for socio-demographic characteristics. Results : Sexual minority adults experienced a higher prevalence of substance use and disorders than heterosexuals. For example, bisexuals were more likely than heterosexuals to use marijuana (AOR = 3.45, 95% CI = 2.64-4.50) and have tobacco use disorders (AOR = 2.58, 95% CI = 2.02-3.28). These associations were stronger among racial/ethnic minorities. For instance, bisexual non-Hispanic Blacks were more than twice as likely (AOR = 3.17, 95% CI = 2.16-4.65) to be current tobacco users than their heterosexual counterparts; while this association was weaker for bisexual non-Hispanic Whites (AOR = 1.99, 95% CI = 1.47-2.71). Conclusion : Sexual minority adults, especially those who are also racial/ethnic minorities, experience a significantly higher burden of substance use and disorders than heterosexuals. Efforts to screen and treat substance use and disorders among this particular population are critically needed to improve their health outcomes and reduce health disparities.

Cytokine and hormone concentrations can be linked to the manipulation of training variables and to subsequent alterations in performance., Subjects: Nine D-1 collegiate throwers and 4 control subjects participated in this preliminary and exploratory report., Methods: Hormone (testosterone (T) and cortisol (C)) and adipokine (adiponectin, leptin, and resistin) measurements were taken at weeks 1, 7, and 11 for the throwers and weeks 1 and 11 for the control group. The throwers participated in an 11-week periodized resistance training and throws program during the fall preparatory period. Volume load was recorded throughout the study., Results: Hormone values did not exhibit statistically significant changes across time; however, there were notable changes for C, the testosterone to cortisol ratio (T:C), and adiponectin., Conclusions: T:C was increased as volume load decreased, and adiponectin increased in concert with decreases in C and increases in the T:C, possibly suggesting a lesser degree of obesity-related inflammation and a higher degree of "fitness" and preparedness.

It is unclear whether health risk behaviors differ by nuanced marital statuses and race/ethnicity. We examined the association between detailed marital status and current cigarette smoking among U.S. adults by race/ethnicity. Data were from four Health Information National Trends (HINTS) study cycles collected in 2011-2017 with a nationally representative sample of adults 30 years and older (n = 11,889). Current cigarette smoking prevalence was compared across detailed marital statuses (married, cohabiting, divorced, widowed, separated, single/never married) by race/ethnicity. Adults who had the highest prevalence of cigarette smoking were non-Hispanic Black cohabitors (36.2%), separated non-Hispanic White adults (35.3%), and single/never married Hispanic adults (28.2%). It is noteworthy that widowed adults had lower cigarette smoking prevalence than those who were divorced or separated across races/ethnicities. Taken together, this study demonstrates how cigarette smoking prevalence varies by intersection of marital status and race/ethnicity. Ensuring the equitable implementation of a comprehensive best-practice tobacco prevention and control program that includes prevention and treatment is important to reduce the burden of cigarette smoking in these populations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Daily undulating periodization (DUP), using daily alterations in repetitions, has been advocated as a superior method of resistance training, while traditional forms of programming for periodization (Block) have been questioned. Nineteen Division I track and field athletes were assigned to either a 10-week Block or DUP training group. Year and event were controlled. Over the course of the study, there were four testing sessions, which were used to evaluate a variety of strength characteristics, including maximum isometric strength, rate of force development, and one repetition maximum (1RM). Although, performance trends favored the Block group for strength and rate of force development, no statistical differences were found between the two groups. However, different ( p ≤ 0.05) estimated volumes of work (VL) and amounts of improvement per VL were found between groups. Based upon calculated training efficiency scores, these data indicate that a Block training model is more efficient in producing strength gains than a DUP model. Additionally, alterations in testosterone (T), cortisol (C) and the T:C ratio were measured. Although there were no statistically ( p ≤ 0.05) different hormone alterations between groups, relationships between training variables and hormone concentrations including the T:C ratio, indicate that Block may be more efficacious in terms of fatigue management., Competing Interests: The authors declare no conflict of interest.

Kavanaugh, AA, Mizuguchi, S, Sands, WA, Ramsey, MW, and Stone, MH. Long-term changes in jump performance and maximum strength in a cohort of NCAA division I women's volleyball Athletes. J Strength Cond Res 32(1): 66-75, 2018-The purpose of this investigation was to quantify the magnitude of change in maximal strength and jumping abilities over approximately 1, 2, and 3 years of supervised sport and resistance training in National Collegiate Athletic Association (NCAA) division I women's volleyball athletes. This was an exploratory study on a cohort of women's volleyball athletes (n = 29) split into 3 groups based on the length of the time spent in a supervised resistance training program: group 1 (n = 11): 0.7 ± 0.3 years, group 2 (n = 9): 1.6 ± 0.2 years, and group 3 (n = 9): 2.4 ± 0.6 years. Monitoring tests consisted of standing height (cm), body mass (kg), body fat (%), static jump height (SJH) and countermovement JH (CMJH) with 0-, 11-, and 20-kg loads (cm), and midthigh clean pull isometric peak force (IPF) and allometrically scaled IPF (IPFa) (N·kg). Increasing trends were observed for all variables from groups 1 to 2 to 3. Statistically greater improvements (p ≤ 0.05) with moderate to large effect sizes were found between groups 1 and 3 for SJH 0 (19.7%, d = 1.35), SJH 11 (23.8%, d = 1.23), SJH 20 (30.6%, d = 1.20), CMJH 11 (22.6%, d = 1.18), IPF (44.4%, d = 1.22), and IPFa (41.2%, d = 1.32). A combination of traditional resistance training exercises and weightlifting variations at various loads, in addition to volleyball practice, seem to be effective at increasing maximal strength by 44% and vertical JH by 20-30% in NCAA division I women's volleyball athletes after about 2.5 years of training. Furthermore, these characteristics can be improved in the absence of additional plyometric training outside normal volleyball-specific practice.

The purpose of this monitoring study was to investigate how alterations in training affect changes in force-related characteristics and weightlifting performance., Subjects: Seven competitive weightlifters participated in the study., Methods: The weightlifters performed a block style periodized plan across 20 weeks. Force plate data from the isometric mid-thigh pull and static jumps with 0 kg, 11 kg, and 20 kg were collected near the end of each training block (weeks 1, 6, 10, 13, 17, and 20). Weightlifting performance was measured at weeks 0, 7, 11, and 20., Results: Very strong correlations were noted between weightlifting performances and isometric rate of force development (RFD), isometric peak force (PF), peak power (PP), and jump height (JH). Men responded in a more predictable manner than the women. During periods of higher training volume, RFD was depressed to a greater extent than PF. JH at 20 kg responded in a manner reflecting the expected fatigue response more so than JH at 0 kg and 11 kg., Conclusions: PF appears to have been more resistant to volume alterations than RFD and JH at 20 kg. RFD and JH at 20 kg appear to be superior monitoring metrics due to their "sensitivity.", Competing Interests: The authors declare no conflicts of interest.

Stuart, CA, Lee, ML, South, MA, Howell, MEA, Cartwright, BM, Ramsey, MW, and Stone, MH. Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798-808, 2017-Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow-twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and glucose transporter type 4 (GLUT4) expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole-body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pretraining baseline., Competing Interests: The authors have no conflict of interest disclosures.

Insulin resistance in metabolic syndrome subjects is profound in spite of muscle insulin receptor and insulin-responsive glucose transporter (GLUT4) expression being nearly normal. Insulin receptor tyrosine kinase phosphorylation of insulin receptor substrate-1 (IRS-1) at Tyr896 is a necessary step in insulin stimulation of translocation of GLUT4 to the cell surface. Serine phosphorylation of IRS-1 by some kinases diminishes insulin action in mice. We evaluated the phosphorylation status of muscle IRS-1 in 33 subjects with the metabolic syndrome and seventeen lean controls. Each underwent euglycemic insulin clamps and a thigh muscle biopsy before and after 8 weeks of either strength or endurance training. Muscle IRS-1 phosphorylation at six sites was quantified by immunoblots. Metabolic syndrome muscle IRS-1 had excess phosphorylation at Ser337 and Ser636 but not at Ser307, Ser789, or Ser1101. Ser337 is a target for phosphorylation by glycogen synthase kinase 3 (GSK3) and Ser636 is phosphorylated by c-Jun N-terminal kinase 1 (JNK1). Exercise training without weight loss did not change the IRS-1 serine phosphorylation. These data suggest that baseline hyperphosphorylation of at least two key serines within muscle IRS-1 diminishes the transmission of the insulin signal and thereby decreases the insulin-stimulated translocation of GLUT4. Excess fasting phosphorylation of muscle IRS-1 at Ser636 may be a major cause of the insulin resistance seen in obesity and might prevent improvement in insulin responsiveness when exercise training is not accompanied by weight loss., (© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Aim: The aim of the study was to investigate the applicability of a repeated change-of-direction (RCoD) test for NCAA Division-I male soccer players., Methods: The RCoD test consisted of 5 diagonal direction changes per repetition with a soccer ball to be struck at the end. Each player performed 15 repetitions with approximately 10 seconds to jog back between repetitions. Data were collected in two sessions. In the first session, 13 players were examined for heart rate responses and blood lactate concentrations. In the second session, 22 players were examined for the test's ability to discriminate the primary from secondary players (78.0±16.1 and 10.4±13.3 minutes per match, respectively)., Results: Heart rate data were available only from 9 players due to artifacts. The peak heart rate (200.2±6.6 beats∙min-1: 99.9±3.0% maximum) and blood lactate concentration (14.8±2.4 mmol∙L-1 immediately after) resulted in approximately 3.5 and 6.4-fold increases from the resting values, respectively. These values appear comparable to those during intense periods of soccer matches. In addition, the average repetition time of the test was found to discriminate the primary (4.85±0.23 s) from the secondary players (5.10±0.24 s) (P=0.02)., Conclusion: The RCoD test appears to induce physiological responses similar to intense periods of soccer matches with respect to heart rate and blood lactate concentration. Players with better average repetition times tend to be those who play major minutes.

Introduction: Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome., Methods: Eighteen nondiabetic, sedentary subjects, 11 with the metabolic syndrome, participated in 8 wk of increasing intensity stationary cycle training., Results: Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (V·O 2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. The activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of type 2× fibers decreased with a concomitant increase in type 2a mixed fibers in the control subjects, but in metabolic syndrome, type 2× fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups, and GLUT4 expression increased in the metabolic syndrome subjects. The excess phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1., Conclusions: In the absence of weight loss, the cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis and increased the expression of insulin receptors and GLUT4 in muscle but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337, and this is not ameliorated by 8 wk of endurance exercise training.

Context: The metabolic syndrome, characterized by central obesity with dyslipidemia, hypertension, and hyperglycemia, identifies people at high risk for type 2 diabetes., Objective: Our objective was to determine how the insulin resistance of the metabolic syndrome is related to muscle fiber composition., Design: Thirty-nine sedentary men and women (including 22 with the metabolic syndrome) had insulin responsiveness quantified using euglycemic clamps and underwent biopsies of the vastus lateralis muscle. Expression of insulin receptors, insulin receptor substrate-1, glucose transporter 4, and ATP synthase were quantified with immunoblots and immunohistochemistry., Participants and Setting: Participants were nondiabetic, metabolic syndrome volunteers and sedentary control subjects studied at an outpatient clinic., Main Outcome Measures: Insulin responsiveness during an insulin clamp and the fiber composition of a muscle biopsy specimen were evaluated., Results: There were fewer type I fibers and more mixed (type IIa) fibers in metabolic syndrome subjects. Insulin responsiveness and maximal oxygen uptake correlated with the proportion of type I fibers. Insulin receptor, insulin receptor substrate-1, and glucose transporter 4 expression were not different in whole muscle but all were significantly less in the type I fibers of metabolic syndrome subjects when adjusted for fiber proportion and fiber size. Fat oxidation and muscle mitochondrial expression were not different in the metabolic syndrome subjects., Conclusion: Lower proportion of type I fibers in metabolic syndrome muscle correlated with the severity of insulin resistance. Even though whole muscle content was normal, key elements of insulin action were consistently less in type I muscle fibers, suggesting their distribution was important in mediating insulin effects.

Adipose tissue (AT), which typically comprises an increased percentage of body mass with advancing age, receives a large proportion of resting cardiac output. During exercise, an old age-associated inability to increase vascular resistance within the intra-abdominal AT may compromise the ability of the cardiovascular system to redistribute blood flow to the active musculature, contributing to the decline in exercise capacity observed in this population. We tested the hypotheses that 1) there would be an elevated perfusion of AT during exercise with old age that was associated with diminished vasoconstrictor responses of adipose-resistance arteries, and 2) chronic exercise training would mitigate the age-associated alterations in AT blood flow and vascular function. Young (6 mo; n = 40) and old (24 mo; n = 28) male Fischer 344 rats were divided into young sedentary (YSed), old sedentary (OSed), young exercise trained (YET), or old exercise trained (OET) groups, where training consisted of 10-12 wk of treadmill exercise. In vivo blood flow at rest and during exercise and in vitro α-adrenergic and myogenic vasoconstrictor responses in resistance arteries from AT were measured in all groups. In response to exercise, there was a directionally opposite change in AT blood flow in the OSed group (≈ 150% increase) and YSed (≈ 55% decrease) vs. resting values. Both α-adrenergic and myogenic vasoconstriction were diminished in OSed vs. YSed AT-resistance arteries. Exercise training resulted in a similar AT hyperemic response between age groups during exercise (YET, 9.9 ± 0.5 ml · min(-1) · 100(-1) g; OET, 8.1 ± 0.9 ml · min(-1) · 100(-1) g) and was associated with enhanced myogenic and α-adrenergic vasoconstriction of AT-resistance arteries from the OET group relative to OSed. These results indicate that there is an inability to increase vascular resistance in AT during exercise with old age, due, in part, to a diminished vasoconstriction of AT arteries. Furthermore, the results indicate that exercise training can augment vasoconstriction of AT arteries and mitigate age-related alterations in the regulation of AT blood flow during exercise.

With old age, blood flow to the high-oxidative red skeletal muscle is reduced and blood flow to the low-oxidative white muscle is elevated during exercise. Changes in the number of feed arteries perforating the muscle are thought to contribute to this altered hyperemic response during exercise. We tested the hypothesis that exercise training would ameliorate age-related differences in blood flow during exercise and feed artery structure in skeletal muscle. Young (6-7 mo old, n = 36) and old (24 mo old, n = 25) male Fischer 344 rats were divided into young sedentary (Sed), old Sed, young exercise-trained (ET), and old ET groups, where training consisted of 10-12 wk of treadmill exercise. In Sed and ET rats, blood flow to the red and white portions of the gastrocnemius muscle (Gast(Red) and Gast(White)) and the number and luminal cross-sectional area (CSA) of all feed arteries perforating the muscle were measured at rest and during exercise. In the old ET group, blood flow was greater to Gast(Red) (264 ± 13 and 195 ± 9 ml · min(-1) · 100 g(-1) in old ET and old Sed, respectively) and lower to Gast(White) (78 ± 5 and 120 ± 6 ml · min(-1) · 100 g(-1) in old ET and old Sed, respectively) than in the old Sed group. There was no difference in the number of feed arteries between the old ET and old Sed group, although the CSA of feed arteries from old ET rats was larger. In young ET rats, there was an increase in the number of feed arteries perforating the muscle. Exercise training mitigated old age-associated differences in blood flow during exercise within gastrocnemius muscle. However, training-induced adaptations in resistance artery morphology differed between young (increase in feed artery number) and old (increase in artery CSA) animals. The altered blood flow pattern induced by exercise training with old age would improve the local matching of O(2) delivery to consumption within the skeletal muscle.

Recently, the comparison of "periodized" strength training methods has been a focus of both exercise and sport science. Daily undulating periodization (DUP), using daily alterations in repetitions, has been developed and touted as a superior method of training, while block forms of programming for periodization have been questioned. Therefore, the purpose of this study is to compare block to DUP in Division I track and field athletes. Thirty-one athletes were assigned to either a 10-wk block or DUP training group in which sex, year, and event were matched. Over the course of the study, there were 4 testing sessions, which were used to evaluate a variety of strength characteristics. Although performance trends favored the block group for strength and rate of force development, no statistically significant differences were found between the 2 training groups. However, statistically different (P ≤ .05) values were found for estimated volume of work (volume load) and the amount of improvement per volume load between block and DUP groups. Based on calculated training efficiency scores, these data indicate that a block training model is more efficient than a DUP model in producing strength gains.

Context: Strength training induces muscle remodeling and may improve insulin responsiveness., Objective: This study will quantify the impact of resistance training on insulin sensitivity in subjects with the metabolic syndrome and correlate this with activation of intramuscular pathways mediating mitochondrial biogenesis and muscle fiber hypertrophy., Design: Ten subjects with the metabolic syndrome (MS) and nine sedentary controls underwent 8 wk of supervised resistance exercise training with pre- and posttraining anthropometric and muscle biochemical assessments., Setting: Resistance exercise training took place in a sports laboratory on a college campus., Main Outcome Measures: Pre- and posttraining insulin responsiveness was quantified using a euglycemic clamp. Changes in expression of muscle 5-AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathways were quantified using immunoblots., Results: Strength and stamina increased in both groups. Insulin sensitivity increased in controls (steady-state glucose infusion rate = 7.0 ± 2.0 mg/kg · min pretraining training vs. 8.7 ± 3.1 mg/kg · min posttraining; P < 0.01) but did not improve in MS subjects (3.3 ± 1.3 pre vs. 3.1 ± 1.0 post). Muscle glucose transporter 4 increased 67% in controls and 36% in the MS subjects. Control subjects increased muscle phospho-AMPK (43%), peroxisome proliferator-activated receptor γ coactivator 1α (57%), and ATP synthase (60%), more than MS subjects (8, 28, and 21%, respectively). In contrast, muscle phospho-mTOR increased most in the MS group (57 vs. 32%)., Conclusion: Failure of resistance training to improve insulin responsiveness in MS subjects was coincident with diminished phosphorylation of muscle AMPK, but increased phosphorylation of mTOR, suggesting activation of the mTOR pathway could be involved in inhibition of exercise training-related increases in AMPK and its activation and downstream events.

Purpose: To investigate the relationship between maximum strength and differences in jump height during weighted and unweighted (body weight) static (SJ) and countermovement jumps (CMJ)., Methods: Sixty-three collegiate athletes (mean +/- SD; age= 19.9 +/- 1.3 y; body mass = 72.9 +/- 19.6 kg; height = 172.8 +/- 7.7 cm) performed two trials of the SJ and CMJ with 0 kg and 20 kg on a force plate; and two trials of mid-thigh isometric clean pulls in a custom rack over a force plate (1000-Hz sampling). Jump height (JH) was calculated from flight time. Force-time curve analyses determined the following: isometric peak force (IPF), isometric force (IF) at 50, 90, and 250 ms, and isometric rates of force development (IRFD). Absolute and allometric scaled forces, [absolute force/(body mass(0.67))], were used in correlations., Results: IPF, IRFD, F50(a), F50, F90, and F250 showed moderate/strong correlations with SJ and CMJ height percent decrease from 0 to 20 kg. IPF(a) and F250(a) showed weak/moderate correlations with percent height decrease. Comparing strongest (n = 6) to weakest (n = 6): t tests revealed that stronger athletes (IPF(a)) performed superior to weaker athletes., Conclusion: Data indicate the ability to produce higher peak and instantaneous forces and IRFD is related to JH and to smaller differences between weighted and unweighted jump heights. Stronger athletes jump higher and show smaller decrements in JH with load. A weighted jump may be a practical method of assessing relative strength levels.

Aim: Bone changes in size and density in response to different levels of stress. Alterations to bone mineral density (BMD) appear to occur in a site specific manner. Even though BMD has been examined in many populations there is a paucity of data looking at strength-power athletes, such as throwers. Therefore, the purpose of this study was to examine the BMD of a group of USA Division I collegiate throwers (e.g. shot put, discus, etc.)., Methods: Seven throwers (4 males; 3 females) who were 19.0 + or - 0.9 years had their BMD compared to an age matched control group (n = 14; 8 women and 6 men) and normative data. BMD was measured with dual X-ray absorptometry. Potential right/left side and sex difference in BMD were also examined. Maximal isometric strength was assessed using a mid-thigh pull while standing on a forceplate which generated force-time curves. Peak force (PF) and normalized peak force (PFa) were then correlated with BMDs., Results: Generally, throwers had denser bones with male throwers tending to have a greater total BMD (P < or = 0.05). The dominant arm BMD was slightly greater when compared to non-dominant arm (P < or = 0.05). Furthermore, total body BMD was related to PF (r = 0.68, r(2) = 0.46) and PFa (r = 0.56, r(2) = 0.31)., Conclusions: Throwers have greater BMDs than non-athletes and most other athletes. However, throwers only showed a small indication of sidedness. It is likely that the BMDs observed in this study stem from the training intervention (e.g. whole body heavy lifting) undertaken by this population.

Purpose: Effects of simultaneous vibration-stretching on flexibility and explosive strength in competitive female gymnasts were examined., Methods: Twenty-two female athletes (age = 11.3 +/- 2.6 yr; body mass = 35.3 +/- 11.6 kg; competitive levels = 3-9) composed the simultaneous vibration-stretching (VS) group, which performed both tests. Flexibility testing control groups were stretching-only (SF) (N = 7) and vibration-only (VF) (N = 8). Explosive strength-control groups were stretching-only (SES) (N = 8) and vibration-only (VES) (N = 7). Vibration (30 Hz, 2-mm displacement) was applied to four sites, four times for 10 s, with 5 s of rest in between. Right and left forward-split (RFS and LFS) flexibility was measured by the distance between the ground and the anterior suprailiac spine. A force plate (sampling rate, 1000 Hz) recorded countermovement and static jump characteristics. Explosive strength variables included flight time, jump height, peak force, instantaneous forces, and rates of force development. Data were analyzed using Bonferroni adjusted paired t-tests., Results: VS had statistically increased flexibility (P) and large effect sizes (d) in both the RFS (P = 1.28 x 10(-7), d = 0.67) and LFS (P = 2.35 x 10(-7), d = 0.72). VS had statistically different results of favored (FL) (P = 4.67 x 10(-8), d= 0.78) and nonfavored (NFL) (P = 7.97 x 10(-10), d = 0.65) legs. VF resulted in statistical increases in flexibility and medium d on RFS (P = 6.98 x 10(-3), d = 0.25) and statistically increased flexibility on VF NFL flexibility (P = 0.002, d = 0.31). SF had no statistical difference between measures and small d. For explosive strength, there were no statistical differences in variables in the VS, SES, and VES for the pre- versus posttreatment tests., Conclusions: Simultaneous vibration and stretching may greatly increase flexibility while not altering explosive strength.

Purpose: This paper attempts to develop production functions (PF) between aerobic exercise inputs and long-run health outputs. Future studies could use such PF for estimating the benefits and costs (broadly defined) of different exercise programs to help develop optimal (utility maximizing) ones., Methods: To develop the PF, the paper reviewed the biomedical literature for the major dose-response relations between health, physical fitness, and exercise. Where relevant, the paper converted the dose-response relationships from relative risks to absolute probabilities and standardized terminology and units of measures., Results: The paper develops a clear set of biological PF that illustrate, quantitatively, how increases in peak cardiorespiratory (CR) fitness as measured by a short stress test reduce the probability of all-cause mortality; how increasing intensities of short (approximately 30 min, three to five times a week) exercise sessions increase peak CR fitness or retard its age-related decline; and how consistent exercise reduces the risk of myocardial infarctions (MI)., Conclusions: The exercise-long-run health PF developed in this paper should provide a useful framework for other studies to estimate the broadly defined costs and benefits of different exercise programs and to help develop optimal ones.

The purpose of this investigation was to determine mean arterial pressure (MAP) and regional vascular conductance responses in young and aged Fisher-344 rats during orthostatic stress, i.e., 70 degrees head-up tilt (HUT). Both groups demonstrated directionally different changes in MAP during HUT (young, 7% increase; aged, 7% decrease). Vascular conductance during HUT in young rats decreased in most tissues but largely remained unchanged in the aged animals. Based on the higher vascular conductance of white adipose tissue from aged rats during HUT, resistance arteries from white visceral fat were isolated and studied in vitro. There was diminished maximal vasoconstriction to phenylephrine and norepinephrine (NE: young, 42 +/- 5%; old, 18 +/- 6%) in adipose resistance arteries from aged rats. These results demonstrate that aging reduces the ability to maintain MAP during orthostatic stress, and this is associated with a diminished vasoconstriction of adipose resistance arteries.

Cerebral hypoxia has been proposed as a mechanism by which prenatal ethanol exposure causes fetal alcohol spectrum disorder (FASD) in children, but no study had tested this hypothesis using a chronic exposure model that mimicks a common human exposure pattern. Pregnant sheep were exposed to ethanol, 0.75 or 1.75 g kg(-1) (to create blood ethanol concentrations of 85 and 185 mg dl(-1), respectively), or saline 3 days per week in succession (a 'binge drinking' model) from gestational day (GD) 109 until GD 132. Fetuses were instrumented on GD 119-120 and studied on GD 132. The 1.75 g kg(-1) dose resulted in a significant increase in fetal biventricular output (measured by radiolabelled microsphere technique) and heart rate, and a reduction of mean arterial pressure and total peripheral resistance at 1 h, the end of ethanol infusion. The arterial partial pressure of CO(2) was increased, arterial pH was decreased and arterial partial pressure of O(2) did not change. Fetal whole-brain blood flow increased by 37% compared with the control group at 1 h, resulting in increased cerebral oxygen delivery. The elevation in brain blood flow was region specific, occurring preferentially in the ethanol-sensitive cerebellum, increasing by 44% compared with the control group at 1 h. There were no changes in the lower dose group. Assessment of regional differences in the teratogenic effects of ethanol by stereological cell-counting technique showed a reduced number of cerebellar Purkinje cells in response to the 1.75 g kg(-1) dose compared with the control brains. However, no such differences in neuronal numbers were observed in the hippocampus or the olfactory bulb. We conclude that repeated exposure to moderate doses of ethanol during the third trimester alters fetal cerebral vascular function and increases blood flow in brain regions that are vulnerable to ethanol in the presence of acidaemia and hypercapnia, and in the absence of hypoxia.

Unlabelled: We determined whether aging diminishes bone blood flow and impairs endothelium-dependent vasodilation. Femoral perfusion was lower in old animals, as well as endothelium-dependent vasodilation and NO bioavailability. These effects could contribute to old age-related bone loss and the increased risk of fracture., Introduction: Aging has been shown to diminish bone blood flow in rats and humans. The purpose of this study was to determine whether blood flow to regions of the femur perfused primarily through the principal nutrient artery (PNA) are diminished with aging and whether this putative reduction in flow is associated with impaired endothelium-dependent vasodilation., Materials and Methods: Blood flow was measured in conscious young adult (4-6 mo old) and aged (24-26 mo old) male Fischer-344 rats using radiolabeled microspheres. Endothelium-dependent vasodilation of the PNA was assessed in vitro using acetylcholine (ACh), whereas the contribution of the NO synthase (NOS) and cyclooxygenase (COX) signaling pathways to endothelium-dependent vasodilation was determined using the NOS and COX inhibitors L-NAME and indomethacin, respectively., Results: Femoral blood flow in the aged rats was 21% and 28% lower in the proximal and distal metaphyses, respectively, and 45% lower in the diaphyseal marrow. Endothelium-dependent vasodilation was reduced with old age (young: 83 +/- 6% maximal relaxation; aged: 62 +/- 5% maximal relaxation), whereas endothelium-independent vasodilation (sodium nitroprusside) was unaffected by age. The reduction in endothelium-dependent vasodilation was mediated through impairment of the NOS signaling pathway, which resulted in lower NO bioavailability (young: 168 +/- 56 nM; aged: 50 +/- 7 nM)., Conclusions: These data show that reductions in metaphyseal bone and diaphyseal marrow perfusion with old age are associated with diminished endothelium-dependent vasodilation through an impairment of the NOS mechanism. Such age-related changes in bone perfusion and vascular NO signaling could impact clinical bone loss, increase risk of fracture, and impair fracture healing in the elderly.

Background: Erectile dysfunction (ED) in diabetes is related to autonomic neuropathy and endothelial dysfunction. We studied the relative importance of these factors in diabetic and non-diabetic men with ED and determined if they predict responses to treatment with sildenafil., Methods: Thirty-three men, aged 35-65 years, with ED (20 diabetic, 13 non-diabetic), 15 of whom were sildenafil responders and 18 non-responders, were compared with 30 age and risk-matched control subjects (15 diabetic, 15 non-diabetic). Subjects with ED completed the International Index of Erectile Function (IIEF) questionnaire. Endothelial function was assessed by changes in brachio-radial and femoro-tibial arterial pulse-wave velocity (pulse-wave velocity) during reactive hyperaemia, expressed as percentage endothelium-dependent dilatation. Autonomic function was assessed by heart rate variation during expiration and inspiration (E/I ratio) and during the valsalva manoeuvre., Results: The respective changes in pulse-wave velocity, in the arm and leg [mean (sd)] were 0.71 (6.5)% and 3.5 (6.4)% in the impotent diabetic men, 0.7 (7.6)% and 2.4 (5.9)% in the non-diabetic impotent men, -0.68 (5.7)% and -1.31 (7.2)% in the non-impotent diabetic men and 7.7 (3.7)% and 7.6 (3.4)% in the control subjects. There was a significant interaction between ED and diabetic status such that there was significantly impaired vascular response in the diabetic group (both with and without ED) and in the non-diabetic group with ED compared with the non-diabetic control group (P = 0.01 and P = 0.001 for brachio-radial and femoro-tibial measures, respectively). The E/I ratios of the diabetic men were significantly lower than those of the control subjects [1.17 (0.14) vs. 1.33 (0.16), P < 0.02), but there were no differences in the measures of autonomic neuropathy between the groups with ED and those with normal erectile function. Amongst diabetic men, the initial IIEF scores (maximum score 30, low score indicates more severe ED) were significantly higher in sildenafil-responders than non-responders [16.3 (8.4), vs. 6.8 (7 1), P < 0.02]. The rate of sildenafil response was not significantly affected by the measures of endothelial or autonomic function., Conclusions: ED in both diabetic and non-diabetic men is characterized by marked endothelial dysfunction in comparison with non-diabetic control subjects. Response to sildenafil is not predicted by either endothelial function or autonomic function, but in diabetic men appears to be related to the initial degree of erectile dysfunction.

Ageing reduces endothelium-dependent vasodilatation in humans and animals, and in humans, exercise training reverses the ageing-associated reduction in endothelium-dependent vasodilatation. The purpose of this study was to determine the mechanism(s) by which 10-12 weeks of treadmill exercise enhances endothelium-dependent vasodilatation in muscles of differing fibre composition from young and old rats. Three- and 22-month-old male Fischer 344 rats were assigned to young sedentary, young exercise-trained, old sedentary, or old exercise-trained groups. Arterioles were isolated from the soleus and gastrocnemius muscles; luminal diameter changes were determined in response to the endothelium-dependent vasodilator acetylcholine (ACh, 10(-9)-10(-4) mol l(-1)) alone and in the presence of the nitric oxide synthase (NOS) inhibitor l-NAME (10(-5) mol l(-1)) or the combination of l-NAME and the cyclooxygenase inhibitor indomethacin (10(-5) mol l(-1)). Training ameliorated the ageing-induced reduction in endothelium-dependent vasodilatation in soleus muscle arterioles. Treatment with l-NAME alone and in combination with indomethacin abolished differences in ACh vasodilatation occurring with ageing and training. Expression of endothelial NOS (eNOS) mRNA in soleus arterioles was unaltered by ageing, whereas eNOS protein was increased with age; training elevated both eNOS mRNA and protein. In gastrocnemius muscle arterioles, ageing did not alter maximal vasodilatation, but ageing and training increased maximal arteriolar diameter. These results demonstrate that ageing-induced reductions and training-induced enhancement of endothelial vasodilatation both occur through the nitric oxide signalling mechanism in highly oxidative skeletal muscle, but ageing and training do not appear to act on the same portion of the signalling cascade.

Blood flow capacity in skeletal muscle declines with age. Reduced blood flow capacity may be related to decline in the maximal vasodilatory capacity of the resistance vasculature. This study tested the hypothesis that aging results in impaired vasodilatory capacity of first-order (1A) arterioles isolated from rat-hindlimb locomotory muscle: 1A arterioles (90-220 microm) from gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-144 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasodilatory responses to increasing concentrations of ACh (10(-9) to 10(-4) M), adenosine (ADO, 10(-10) to 10(-4) M), and sodium nitroprusside (SNP, 10(-10) to 10(-4) M) were evaluated at a constant intraluminal pressure of 60 cmH(2)O in the absence of flow. Flow-induced vasodilation was also evaluated in the absence of pressure changes. Responses to ADO and SNP were not altered by age. Endothelium-dependent vasodilation induced by flow was significantly reduced in arterioles from both gastrocnemius and soleus muscles. In contrast, endothelium-dependent vasodilation to ACh was reduced only in soleus muscle arterioles. These results indicate that aging impairs vasodilatory responses mediated through the endothelium of resistance arterioles from locomotory muscle, whereas smooth muscle vasodilatory responses remain intact with aging. Additionally, ACh-induced vasodilation was altered by age only in soleus muscle arterioles, suggesting that the mechanism of age-related endothelial impairment differs in arterioles from soleus and gastrocnemius muscles.

Ventricular septal defect (VSD) is a rare but serious complication of acute myocardial infarction requiring early surgical intervention. A patient with acquired VSD that spontaneously closed over three months is presented. The literature on spontaneous closure of acquired VSDs is also reviewed.

Exercise capacity and skeletal muscle blood flow during exercise are reduced with advancing age. This reduction in blood flow capacity may be related to increased reactivity of skeletal muscle resistance vessels to vasoconstrictor stimuli. The purpose of this study was to test the hypothesis that aging results in increased vasoconstrictor responses of skeletal muscle resistance arterioles. First-order (1A) arterioles (90-220 microm) from the gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-344 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasoconstriction in response to increases in norepinephrine (NE; 1 x 10(-9)-1 x 10(-4) M) and KCl (20-100 mM) concentrations and increases in intraluminal pressure (10-130 cmH(2)O) were evaluated in the absence of flow. Responses to NE and KCl were similar in both soleus and gastrocnemius muscle arterioles from young and aged rats. In contrast, active myogenic responses to changes in intraluminal pressure were diminished in soleus and gastrocnemius arterioles from aged rats. To assess whether alterations in the mechanical properties of resistance arterioles underlie altered myogenic responsiveness, passive diameter responses to pressure and mechanical stiffness were evaluated. There was no effect of age on the structural behavior (passive pressure-diameter relationship) or stiffness of arterioles from either the soleus or gastrocnemius muscles. These results suggest that aging does not result in a nonspecific decrease in vasoconstrictor responsiveness of skeletal muscle arterioles. Rather, aging-induced adaptations of vasoreactivity of resistance arterioles appear to be limited to mechanisms that are uniquely involved in the signaling of the myogenic response.

Objective: This work was undertaken to determine whether dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia., Background: Marine omega-3 fatty acids improve vascular function, but the underlying mechanism(s) are unclear. We studied the effects of marine omega-3 fatty acids on large artery endothelial function in subjects with hypercholesterolemia., Methods: Hypercholesterolemic subjects with no other known cause for endothelial dysfunction were recruited to a prospective, placebo-controlled, randomized, double-blind, parallel-group study. Treatment with omega-3 fatty acids at a dose of 4 g/day (n = 15/group) was compared with placebo, at the beginning (day 0) and end (day 120) of a four-month treatment period. Endothelial function was assessed pre- and posttreatment by noninvasive ultrasonic vessel wall tracking of brachial artery flow-mediated dilation (FMD)., Results: Treatment with marine omega-3 fatty acids resulted in a significant improvement in FMD (0.05 +/- 0.12 to 0.12 +/- 0.07 mm, p < 0.05) and a significant reduction in triglycerides (2.07 +/- 1.13 to 1.73 +/- 0.95 mmol/liter, p < 0.05), whereas treatment with placebo resulted in no change in FMD (0.03 +/- 0.10 to 0.04 +/- 0.10 mm) or triglycerides (2.29 +/- 2.09 to 2.05 +/- 1.36 mmol/liter) (both p < 0.05 treated compared with control). Responses to sublingual glyceryl trinitrate were unchanged., Conclusions: Marine omega-3 fatty acids improve large artery endothelium-dependent dilation in subjects with hypercholesterolemia without affecting endothelium-independent dilation.

Background: Elevated plasma homocysteine (Hcy) is a risk factor for vascular disease. A postulated mechanism is vascular endothelial damage by homocysteine. Hcy levels are inversely related to blood concentrations of folate and can be lowered by folate supplements. The effect of oral folic acid on endothelial function was investigated in healthy adults with mild hyperhomocysteinaemia., Patients and Methods: Eighteen healthy subjects (Hcy > 13 micromol L-1 at entry), from a screening population of 890 volunteers, were entered into a randomised double-blind placebo-controlled crossover study of oral folic acid (5 mg daily for six weeks) with a six week interval between treatments. Flow-mediated (endothelium-dependent) and (endothelial-independent) glyceryl trinitrate (GTN)-mediated brachial artery dilatation were measured by high resolution wall tracking., Results: Folate supplementation enhanced endothelium-dependent responses (+0.08 +/- 0.05 vs. +0.04 +/- 0.04 mm, P = 0.015) but endothelium-independent responses (GTN) were unchanged. Folate reduced Hcy (8.7 +/- 2.5 vs. 12.1 +/- 3.6 micromol L-1)., Conclusion: High dose folic acid supplementation enhances endothelium-dependent vascular function and lowers plasma Hcy. This provides preliminary evidence that folate may have beneficial cardiovascular effects in adults with mild hyperhomocysteinaemia.

Background: The cardiovascular complications of Marfan syndrome arise due to alterations in the structural and functional properties of fibrillin, a constituent of vascular connective tissues. Fibrillin-containing microfibrils are closely associated with arterial endothelial cells, indicating a possible functional role for fibrillin in the endothelium. Plasma concentrations of endothelial cell products are elevated in Marfan subjects, which indirectly indicates endothelial dysfunction. This study directly assessed flow- and agonist-mediated endothelium-dependent brachial artery reactivity in Marfan subjects., Methods and Results: In 20 Marfan and 20 control subjects, brachial artery diameter, blood flow, and blood pressure were measured by ultrasonic wall tracking, Doppler ultrasound, and photoplethysmography, respectively. Measurements were taken during hand hyperemia (a stimulus for endothelium-derived nitric oxide [NO] release in the upstream brachial artery) and after sublingual administration of the endothelium-independent vasodilator nitroglycerin. In 9 Marfan and 6 control subjects, the above parameters were also assessed during intra-arterial infusions of acetylcholine and bradykinin (agonists that stimulate NO production) and NG-monomethyl-L-arginine (L-NMMA, an inhibitor of NO production). Flow-mediated responses differed markedly between Marfan and control subjects (-1.6+/-3.5% versus 6. 50+/-4.1%, respectively; P<0.0001), whereas nitroglycerin produced similar vasodilation (14.2+/-5.7% versus 15.2+/-7.8%; P=NS). Agonist-induced vasodilation to incremental intra-arterial infusions of acetylcholine and bradykinin were not significantly different between Marfan and control subjects, and intra-arterial L-NMMA produced similar reductions in brachial artery diameter in both groups., Conclusions: These data demonstrate impaired flow-mediated but preserved agonist-mediated endothelium-dependent vasodilation in Marfan subjects and suggest preservation of basal NO release. Selective loss of flow-mediated dilation suggests a role for fibrillin in endothelial cell mechanotransduction.

Objective: Non-insulin-dependent diabetes, hypertension and ischaemic heart disease, with insulin resistance, are associated with low birth weight (the 'Small Baby Syndrome'). Common to these adult clinical conditions is endothelial dysfunction. We tested the hypothesis that endothelial dysfunction could precede their development in those of low birth weight., Methods: Endothelial function was measured by ultrasonic 'wall-tracking' of flow-related brachial artery dilatation in fit 19-20 year old subjects randomly selected (blind to the investigators throughout the study) from low (< 2.5 kg) and normal (3.0-3.8 kg) birth weight subjects in the 1975-7 cohort of the Cardiff Births Survey and with no known cause for endothelial dysfunction., Results: Flow-related dilatation was impaired in low birth weight relative to normal birth weight subjects (median 0.04 mm [1.5%] [n = 22] cf. 0.11 mm [4.1%] [n = 17], p < 0.05; 0.04 mm [1.5%] [n = 15] cf. 0.12 mm [4.4%] [n = 12], p < 0.05 after exclusion of inadvertently included ever-smokers)., Conclusion: The findings suggest that endothelial dysfunction is a consequence of foetal malnutrition, consistent with contributing to the clinical features of the 'Small Baby Syndrome' in later adult life.

Background: Elevated plasma homocysteine is a risk factor for arteriosclerosis, but a cause-and-effect relationship remains to be fully established. Endothelial dysfunction, an early event in the atherogenic process, has been shown to be associated with hyperhomocysteinemia in experimental and human studies. To further establish a direct relationship between changes in plasma homocysteine and endothelial dysfunction, we investigated whether moderate hyperhomocysteinemia induced by an oral methionine load would acutely impair flow-mediated endothelium-dependent vasodilatation in healthy adults., Methods and Results: Twenty-four healthy volunteers completed a randomized crossover study in which an oral methionine load (0.1 g/kg) was administered on 1 of 2 study days, 7 days apart. At each visit, plasma homocysteine and brachial artery endothelium-dependent and -independent dilatation were measured at baseline and at 4 hours. To further elucidate the temporal relationship between methionine, homocysteine, and endothelial function, an oral methionine load was administered in 10 subjects on a separate visit, and the time courses of plasma methionine, homocysteine, and flow-mediated brachial artery dilatation were measured at baseline and after 1, 2, 3, 4, and 8 hours. After oral methionine, plasma homocysteine increased from 7. 9+/-2.0 micromol/L at baseline to 23.1+/-5.4 micromol/L at 4 hours (P<0.0001, n=24) and was associated with a decrease in flow-mediated brachial artery dilatation from 0.12+/-0.09 to 0.06+/-0.09 mm (P<0. 05). The time course of the impairment of flow-mediated vasodilatation mirrored the time course of the increase in homocysteine concentration., Conclusions: Oral methionine loading raises plasma homocysteine and impairs flow-mediated endothelium-dependent vasodilatation. This supports the view that homocysteine may promote vascular disease by inducing endothelial dysfunction.

Wave intensity analysis has been applied to the study of arterial hemodynamics. It is a measure of the power transported by waves as they propagate within the arteries and may provide quantitative information about both upstream and downstream conditions. This paper discusses the physical meaning of wave intensity, its measurement using invasive and noninvasive methods, and the effects of physical and pharmacological interventions.

Objective: Diuretics, angiotensin converting enzyme inhibitors and digoxin have become "standard" triple therapy for many patients with chronic cardiac failure. Flosequinan increases exercise duration and improves symptoms when added to standard triple therapy. Despite intensive study, the clinical pharmacology of flosequinan remains uncertain., Setting: The University Hospital of Wales, a Regional Cardiac Centre., Patients: Twenty four patients with chronic heart failure who remained symptomatic despite standard therapy including ACE inhibitors., Methods: A double-blind placebo-controlled parallel group study of 100 mg daily of flosequinan. We measured changes in exercise duration using cardiorespiratory exercise testing and changes in large artery distensibility using Doppler ultrasound., Results: Exercise duration after 8 weeks flosequinan treatment was significantly greater than following placebo treatment. The flosequinan-related increase in exercise duration (+14%) was associated with a significant reduction in VE/VCO2 slope (-16%). Brachial-radial pulse wave velocities were unaltered by flosequinan treatment., Conclusions: Our results confirm that flosequinan improves exercise duration in patients with chronic heart failure. They suggest that this observed beneficial effect is independent of any change in large artery distensibility and that in the presence of ACE inhibitors, this improvement may be independent of any vasodilating action of flosequinan. Although this study confirms the beneficial symptomatic effects of flosequinan in chronic cardiac failure, clinical trials have subsequently demonstrated an overall increase in mortality in patients treated with 100 mg flosequinan daily. This has resulted in the withdrawal of flosequinan from routine clinical use.

Background: Vascular tone is a determinant of conduit artery distensibility. The aim of this study was to establish whether endothelium-derived relaxing factor (EDRF) influences the distensibility of conduit arteries and whether endothelium-mediated increases in distensibility are impaired in chronic heart failure (CHF)., Methods and Results: Conduit artery distensibility was measured by two methods in healthy subjects and in nine patients with CHF caused by dilated cardiomyopathy. In the first method, pulse-wave velocity (PWV) was measured in the right common iliac artery at rest and during local infusions of acetylcholine (10(-7) to 10(-5) mol/L) or adenosine (2 x 10(-7) to 2 x 10(-5) mol/L), with correction for systemic effects. Acetylcholine induced concentration-dependent local reductions of PWV in healthy subjects (-5%, -15%, and -26%) but not in CHF patients (3%, 1%, -4%, P < .01), whereas adenosine induced similar reductions of PWV in healthy subjects and CHF patients. In the second method, brachial artery diameter, blood flow, and blood pressure were measured noninvasively by high-resolution ultrasound, continuous-wave Doppler, and photoplethysmography during reactive hyperemia in the hand and after sublingual glyceryl trinitrate (GTN, 400 micrograms). Hyperemic flow, similar in healthy subjects and CHF patients, was associated with increases in diameter and distensibility in healthy subjects (8.8% and 18.4%, respectively) but not in CHF patients (0.3% and -4.5%), whereas GTN induced similar effects in healthy subjects and CHF patients., Conclusions: These data indicate that conduit artery distensibility is increased by acetylcholine and increased blood flow in healthy subjects but not in CHF patients, whereas the effects of adenosine and GTN on distensibility are preserved in CHF patients. This implies that EDRF-mediated increases in distensibility are impaired in CHF patients, thus adding to cardiac work.

Instrumentation for the real-time clinical measurement of pulse wave velocity (PWV) from intra-arterial pressure waveforms is presented. This time delay between pressure waveforms (obtained from two intra- arterial catheter-mounted transducers 5 cm apart) is calculated by a transputer using multiple comparisons between discrete sections of the waveforms. The method is validated by analysis of digital and analogue signals with known time delays and is used to measure changes in PWV in the right common iliac artery (RCIA) during infusions of acetylcholine (2.4, 24 and 240 micrograms ml-1) in six healthy subjects. The system measures the delay between digitally shifted triangular waveforms and pressure waveforms to a precision of about 50 microseconds, and it is superior to measurements performed by hand using a high-performance digital storage oscilloscope. When used to measure the effects of acetylcholine on the RCIA, dose-dependent reductions in PWV are recorded (-85%, -11.6%, -14.5%). It is concluded that the instrumentation enables PWV to be measured with high accuracy and precision in real time, if the pressure signals are of high fidelity and the relative amplification of the signals is carefully balanced.

A system for the measurement of arterial pulse wave velocity is described. A personal computer (PC) plug-in transputer board is used to process the audio signals from two pocket Doppler ultrasound units. The transputer is used to provide a set of bandpass digital filters on two channels. The times of excursion of power through thresholds in each filter are recorded and used to estimate the onset of systolic flow. The system does not require an additional spectrum analyser and can work in real time. The transputer architecture provides for easy integration into any wider physiological measurement system.