Cerebrovascular reactivity after cessation of menopausal hormone treatment.

OBJECTIVE: Women who are currently using menopausal hormone therapy (MHT) have higher cerebrovascular reactivity when compared with postmenopausal women who are not taking MHT; however, the effect of cessation of MHT on cerebrovascular reactivity is not known. Given that MHT can have structural and activational effects on vascular function, this study was performed to characterize cerebrovascular reactivity following cessation of MHT in women at low risk for cerebrovascular disease. METHODS: Cerebrovascular reactivity was measured in a subset of women from the Kronos Early Estrogen Prevention Study (KEEPS) 3 years after cessation of the study drug (oral conjugated equine estrogen, transdermal 17ß-estradiol, or placebo [PLA]). RESULTS: Age, body mass index, and blood pressure were comparable among groups. At rest, the middle cerebral artery velocity (MCAv), cerebrovascular conductance index, mean arterial pressure, and cerebral pulsatility index did not differ among groups. Slope-based summary measures of cerebrovascular reactivity did not differ significantly among groups. However, utilizing repeated-measures modeling, there was a significant upward shift in MCAv responses (p = 0.029) in the combined MHT group compared with the PLA group. CONCLUSION: MHT has a marginal sustained effect on cerebrovascular reactivity when measured 3 years after cessation of hormone treatment.

Food addiction in children: Associations with obesity, parental food addiction and feeding practices.

Food addiction research in children is limited, and to date addictive-like eating behaviors within families have not been investigated. The aim of this study is to understand factors associated with addictive-like eating in children. The association between food addiction in children with obesity, parental food addiction, and parental feeding practices (i.e., restriction, pressure to eat, monitoring) was investigated. Parents/primary caregivers (aged≥18years) of children aged 5-12years, recruited and completed an online cross-sectional survey including demographics, the Yale Food Addiction Scale (YFAS), and the Child Feeding Questionnaire (CFQ). Parents, reporting on themselves and one of their children, were given a food addiction diagnosis and symptom score according to the YFAS predefined criteria. The total sample consisted of 150 parents/primary caregivers (48% male) and 150 children (51% male). Food addiction was found to be 12.0% in parents and 22.7% in children. In children, food addiction was significantly associated with higher child BMI z-scores. Children with higher food addiction symptoms had parents with higher food addiction scores. Parents of FA children reported significantly higher levels of Restriction and Pressure to eat feeding practices, but not Monitoring. Children with elevated YFAS-C scores may be at greater risk for eating-related issues.

Biology of VO2 max: looking under the physiology lamp.

In this review, we argue that several key features of maximal oxygen uptake (VO2 max) should underpin discussions about the biological and reductionist determinants of its interindividual variability: (i) training-induced increases in VO2 max are largely facilitated by expansion of red blood cell volume and an associated improvement in stroke volume, which also adapts independent of changes in red blood cell volume. These general concepts are also informed by cross-sectional studies in athletes that have very high values for VO2 max. Therefore, (ii) variations in VO2 max improvements with exercise training are also likely related to variations in these physiological determinants. (iii) All previously untrained individuals will respond to endurance exercise training in terms of improvements in VO2 max provided the stimulus exceeds a certain volume and/or intensity. Thus, genetic analysis and/or reductionist studies performed to understand or predict such variations might focus specifically on DNA variants or other molecular phenomena of relevance to these physiological pathways.

Sex differences in elite swimming with advanced age are less than marathon running.

The sex difference in marathon performance increases with finishing place and age of the runner but whether this occurs among swimmers is unknown. The purpose was to compare sex differences in swimming velocity across world record place (1st-10th), age group (25-89 years), and event distance. We also compared sex differences between freestyle swimming and marathon running. The world's top 10 swimming times of both sexes for World Championship freestyle stroke, backstroke, breaststroke, and butterfly events and the world's top 10 marathon times in 5-year age groups were obtained. Men were faster than women for freestyle (12.4 ± 4.2%), backstroke (12.8 ± 3.0%), and breaststroke (14.5 ± 3.2%), with the greatest sex differences for butterfly (16.7 ± 5.5%). The sex difference in swimming velocity increased across world record place for freestyle (P < 0.001), breaststroke, and butterfly for all age groups and distances (P < 0.001) because of a greater relative drop-off between first and 10th place for women. The sex difference in marathon running increased with the world record place and the sex difference for marathon running was greater than for swimming (P < 0.001). The sex difference in swimming increased with world record place and age, but was less than for marathon running. Collectively, these results suggest more depth in women's swimming than marathon running.

The Copenhagen Muscle Research Centre (CMRC) 1994-2004.

This paper presents an impressionistic summary of the formation, activities, accomplishments, and impact of the Copenhagen Muscle Research Centre (CMRC) from 1994 to 2004. The history of the CMRC is viewed in the context of the goals of the original program, the tradition of excellence in exercise physiology in Copenhagen since the time of August Krogh, and the structure of the center. The key role of Professor Bengt Saltin as a visionary, flexible, and inclusive leader is highlighted.

Comparing Cardiopulmonary Exercise Testing in End-Stage Liver Disease Patients.

UNLABELLED: Poor cardiopulmonary fitness has been associated with worse outcomes in liver transplant candidates. PURPOSE: To determine if a modified 3-minute step test (potentially office based) is feasible and equivalent to standard cardiopulmonary exercise testing (CPET) in liver transplant candidates with severe decompensation. METHODS: Five patients with Childs-Pugh C end-stage liver disease and severe debility awaiting liver transplantation performed both standard CPET and the modified 3-minute step test (Shape medical systems). RESULTS: All 5 patients were able to complete both tests. Mean age was 59.8 ± 9 years, mean MELD score was 20 (range 13-26), and mean BMI was 27.6 kg/m(2) (range 16.4-37.2). Peak Vo2 was similar with a mean of 901 mL/min (step test) compared to 856 mL/min (cycle test), P = .64. Vo2 at a respiratory exchange ratio (RER) of 1.0 was similar with both tests (681 mL/min (step) vs 646 mL/min (cycle), P = .69. Ve/Vco2 slope (ventilatory efficiency) was similar (40 vs 39, P = .94). The ventilatory compensation point (i.e. anaerobic threshold) was also similar (∼80% of peak Vo2) for both studies. CONCLUSION: The modified 3-minute step test provides a simplified, potentially office-based assessment of cardiopulmonary exercise capacity and gas exchange measures as standard testing in patients with decompensated end-stage liver disease, with similar tolerability.

Determination of blood volume by pulse CO-oximetry.

The objective of this study was to determine whether changes in carboxyhaemoglobin (COHb) saturation following carbon monoxide (CO) rebreathing can be accurately detected by pulse CO-oximetry in order to determine blood volume. Noninvasive measurements of carboxyhaemoglobin saturation (SpCO) were continuously monitored by pulse CO-oximetry before, during and following 2 min of CO rebreathing. Reproducibility and accuracy of noninvasive blood volume measurements were determined in 16 healthy non-smoking individuals (15 males, age: 28 ± 2 years, body mass index: 25.4 ± 0.6 kg m(-2)) through comparison with blood volume measurements calculated from invasive measurements of COHb saturation. The coefficient of variation for noninvasive blood volume measurements performed on separate days was 15.1% which decreases to 9.1% when measurements were performed on the same day. Changes in COHb saturation and SpCO following CO rebreathing were strongly correlated (r = 0.90, p < 0.01), resulting in a significant correlation between invasive and noninvasive blood volume measurements (r = 0.83, p = 0.02). Changes in SpCO following CO rebreathing can be accurately detected by pulse CO-oximetry, which could potentially provide a simplified, convenient and reproducible method to rapidly determine blood volume in healthy individuals.

The two-hour marathon: who and when?

Whoever breaks 2 h will likely have outstanding running economy and small body size along with exposure to high altitude and significant physical activity early in life. However, neither of these factors nor any specific suite of genotypes appear to be obligatory for a time this fast. Current trends suggest that an East African will be the first to break 2 h. However periods of regional dominance in distance running are not unique to the East Africans: athletes from Finland, Eastern Europe, Australia, and New Zealand have all had extended periods of success at a range of distances. From a physiological perspective, more information is clearly needed on the relationship between VO(2max) and running economy and the influence of running economy and body size on thermoregulation and fuel use.

Relationship between breathing and cardiovascular function at rest: sex-related differences.

AIM: to compare relationships at rest between breathing rate, levels of muscle sympathetic nerve activity, total peripheral resistance and cardiac output among young men and women. METHODS: recordings were made of respiratory movements, sympathetic nerve activity (peroneal microneurography), intra-arterial blood pressure, electrocardiogram, cardiac output (open-circuit acetylene uptake technique) in 19 healthy men (age 27 (+/-) 2years, mean (+/-) SEM) and 17 healthy women (age 25 (+/-) 1years). Total peripheral resistance and stroke volume were calculated. Four minutes epochs of data were analysed. RESULTS: breathing rates and sympathetic activity were similar in men and women but compared to men, women had significantly lower blood pressures, cardiac output and stroke volume. In men breathing rate correlated positively with sympathetic activity (r = 0.58, P < 0.05) but not in women (r = 0.12, P > 0.05). Furthermore, in men, respiratory rate correlated positively with total peripheral resistance (r = 0.65, P < 0.05) and inversely with cardiac output (r =-0.84, P < 0.05) and heart rate (r = -0.60, P < 0.05) but there were no such relationships in women (P > 0.05 for all). CONCLUSIONS: the positive relationship between breathing and sympathetic activity in men, and the inverse coupling of breathing to cardiac output and heart rate suggest that influences of respiration may be important not only for dynamic but also for 'tonic' cardiovascular function. The lack of relationships among these variables in women shows that there are fundamental differences in basic blood pressure regulation between the sexes.

Disparity in regional and systemic circulatory capacities: do they affect the regulation of the circulation?

In this review we integrate ideas about regional and systemic circulatory capacities and the balance between skeletal muscle blood flow and cardiac output during heavy exercise in humans. In the first part of the review we discuss issues related to the pumping capacity of the heart and the vasodilator capacity of skeletal muscle. The issue is that skeletal muscle has a vast capacity to vasodilate during exercise [approximately 300 mL (100 g)(-1) min(-1)], but the pumping capacity of the human heart is limited to 20-25 L min(-1) in untrained subjects and approximately 35 L min(-1) in elite endurance athletes. This means that when more than 7-10 kg of muscle is active during heavy exercise, perfusion of the contracting muscles must be limited or mean arterial pressure will fall. In the second part of the review we emphasize that there is an interplay between sympathetic vasoconstriction and metabolic vasodilation that limits blood flow to contracting muscles to maintain mean arterial pressure. Vasoconstriction in larger vessels continues while constriction in smaller vessels is blunted permitting total muscle blood flow to be limited but distributed more optimally. This interplay between sympathetic constriction and metabolic dilation during heavy whole-body exercise is likely responsible for the very high levels of oxygen extraction seen in contracting skeletal muscle. It also explains why infusing vasodilators in the contracting muscles does not increase oxygen uptake in the muscle. Finally, when approximately 80% of cardiac output is directed towards contracting skeletal muscle modest vasoconstriction in the active muscles can evoke marked changes in arterial pressure.

Integrative mechanisms of blood pressure regulation in humans and rats: cross-species similarities.

As our understanding of the importance of individualized medicine continues to grow, the clinical relevance of interindividual variability in hemodynamic variables is receiving increasing attention. However, it is not known whether the rat, which is often used for studies of cardiovascular regulation, exhibits similar interindividual variability. In the present study, we evaluated whether the magnitude of interindividual variability in cardiac output (CO) and total peripheral resistance (TPR) was similar in humans and in rats. We assessed interindividual variability of mean arterial pressure (MAP), CO, and TPR during control conditions in normotensive humans (n = 40) and during normotension and deoxycorticosterone acetate-salt hypertension in Sprague-Dawley rats (n = 16). Humans and rats showed marked interindividual variability in CO and TPR but low variability in MAP. During deoxycorticosterone acetate-salt hypertension, CO was maintained, but TPR was elevated compared with the baseline period. We conclude that the magnitudes of interindividual variability of MAP, CO, and TPR are quantitatively similar in humans and rats, providing support for the relevance of this variability in both species and suggesting that studies in rats could be designed to address questions specific to individualized medicine in hypertension.

Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade.

The purpose of this study was to compare ganglionic blockade with trimethaphan (TMP) and an alternative drug strategy using combined muscarinic antagonist (glycopyrrolate, GLY) and alpha-2 agonist (dexmedetomidine, DEX). Protocol 1: incremental phenylephrine was administered during control and combined GLY-DEX, or control and TMP on two control combined GLY and DEX or TMP infusion on two randomized days. Protocol 2: muscle sympathetic nerve activity (MSNA) and the baroreflex MSNA relationship was determined before and after GLY-DEX. Blood pressure was higher with GLY-DEX (99+/-3 mm Hg) and lower with TMP (78+/-3 mm Hg) relative to control (GLY-DEX: 90+/-2 mm Hg; TMP: 91+/-2 mm Hg; P<0.05). Incremental phenylephrine increased pressure during GLY-DEX (P<0.01 vs control) and TMP (P<0.01 vs control) to a similar degree. Both GLY-DEX and TMP infusion inhibited norepinephrine release (P<0.01 vs control). GLY-DEX inhibited baseline MSNA (P<0.05) and baroreflex changes in MSNA (P<0.01). We conclude that the GLY-DEX alternative drug strategy can be used as a reasonable alternative to pharmacologic ganglionic blockade to examine autonomic cardiovascular control.

Gait and balance of transfemoral amputees using passive mechanical and microprocessor-controlled prosthetic knees.

BACKGROUND: Microprocessor-controlled knee joints appeared on the market a decade ago. These joints are more sophisticated and more expensive than mechanical ones. The literature is contradictory regarding changes in gait and balance when using these sophisticated devices. METHODS: This study employed a crossover design to assess the comparative performance of a passive mechanical knee prosthesis compared to a microprocessor-controlled knee joint in 15 subjects with an above-knee amputation. Objective measurements of gait and balance were obtained. RESULTS: Subjects demonstrated significantly improved gait characteristics after receiving the microprocessor-controlled prosthetic knee joint (p<0.01). Improvements in gait were a transition from a hyperextended knee to a flexed knee during loading response which resulted in a change from an internal knee flexor moment to a knee extensor moment. The participants' balance also improved (p<0.01). All conditions of the Sensory Organization Test (SOT) demonstrated improvements in equilibrium score. The composite score also increased. CONCLUSIONS: Transfemoral amputees using a microprocessor-controlled knee have significant improvements in gait and balance.

Large variation in t(11;14)(q13;q32) and t(14;18)(q32;q21) translocation product size is confirmed by sequence analysis of PCR products.

Polymerase chain reaction is commonly used to detect t(11;14)(q13;q32) and t(14;18)(q32;q21) chromosomal translocations associated with mantle cell lymphoma and follicular lymphoma. We tested a total of 482 samples from patients with suspected non-Hodgkin's lymphoma and sequenced unusual-sized t(11;14)(q13;q32) and t(14;18)(q32;q21) products from 33 of these patients. BCL-1 or BCL-2 gene rearrangements were confirmed in 23 of 33 patients (70%). Considerable size variation was observed using t(11;14) primers, with MTCA and MTCB t(11;14) products ranging from 234 to 934 bp and 143 to 560 bp respectively. Less variability was observed for t(14;18) Major Breakpoint Region (MBR) products (100-252 bp) but Minor Cluster Region (MCR) products ranged from 217 to 498 bp. We demonstrate the utility of sequence analysis to confirm unusual-sized translocation products and reduce false-positive results because of nonspecific amplification.

Relationship between muscle sympathetic nerve activity and systemic hemodynamics during nitric oxide synthase inhibition in humans.

Large interindividual differences exist in resting sympathetic nerve activity (SNA) among normotensive humans with similar arterial pressure (AP). We recently showed inverse relationships of resting SNA with cardiac output (CO) and vascular adrenergic responsiveness that appear to balance the influence of differences in SNA on blood pressure. In the present study, we tested whether nitric oxide (NO)-mediated vasodilation has a role in this balance by evaluating hemodynamic responses to systemic NO synthase (NOS) inhibition in individuals with low and high resting muscle SNA (MSNA). We measured MSNA via peroneal microneurography, CO via acetylene uptake and AP directly, at baseline and during increasing systemic doses of the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). Baseline MSNA ranged from 9 to 38 bursts/min (13 to 68 bursts/100 heartbeats). L-NMMA caused dose-dependent increases in AP and total peripheral resistance and reflex decreases in CO and MSNA. Increases in AP with L-NMMA were greater in individuals with high baseline MSNA (PANOVA<0.05). For example, after 8.5 mg/kg of L-NMMA, in the low MSNA subgroup (n=6, 28+/-4 bursts/100 heartbeats), AP increased 9+/-1 mmHg, whereas in the high-MSNA subgroup (n=6, 58+/-3 bursts/100 heartbeats), AP increased 15+/-2 mmHg (P<0.01). The high-MSNA subgroup had lower baseline CO and smaller decreases in CO with L-NMMA, but changes in total peripheral resistance were not different between groups. We conclude that differences in CO among individuals with varying sympathetic traffic have important hemodynamic implications during disruption of NO-mediated vasodilation.

Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans.

In humans, sympathetic nerve activity (SNA) at rest can vary several-fold among normotensive individuals with similar blood pressures. We recently showed that a balance exists between SNA and cardiac output, which may contribute to the maintenance of normal blood pressures over the range of resting SNA levels. In the present studies, we assessed whether variability in vascular adrenergic responsiveness has a role in this balance. We tested the hypothesis that forearm vascular responses to noradrenaline (NA) and tyramine (TYR) are related to SNA such that individuals with lower resting SNA have greater adrenergic responsiveness, and vice-versa. We measured multifibre muscle SNA (MSNA; microneurography), arterial pressure (brachial catheter) and forearm blood flow (plethysmography) in 19 healthy subjects at baseline and during intrabrachial infusions of NA and TYR. Resting MSNA ranged from 6 to 34 bursts min(-1), and was inversely related to vasoconstrictor responsiveness to both NA (r = 0.61, P = 0.01) and TYR (r = 0.52, P = 0.02), such that subjects with lower resting MSNA were more responsive to NA and TYR. We conclude that interindividual variability in vascular adrenergic responsiveness contributes to the balance of factors that maintain normal blood pressure in individuals with differing levels of sympathetic neural activity. Further understanding of this balance may have important implications for our understanding of the pathophysiology of hypertension.

Interactions of plasma osmolality with arterial and central venous pressures in control of sympathetic activity and heart rate in humans.

Plasma osmolality alters control of sympathetic activity and heart rate in animal models; however, it is unknown whether physiological increases in plasma osmolality have such influences in humans and what effect concurrent changes in central venous and/or arterial pressures may have. We tested whether physiological increases in plasma osmolality (similar to those during exercise dehydration) alter control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in humans. We studied 17 healthy young adults (7 women, 10 men) at baseline and during arterial pressure (AP) transients induced by sequential injections of nitroprusside and phenylephrine, under three conditions: control (C), after 1 ml/kg intravenous hypertonic saline (HT1), and after 2 ml/kg hypertonic saline (HT2). We continuously measured HR, AP, central venous pressure (CVP; peripherally inserted central catheter) and MSNA (peroneal microneurography) in all conditions. Plasma osmolality increased from 287 +/- 1 mosmol/kg in C to 290 +/- 1 mosmol/kg in HT1 (P < 0.05) but did not increase further in HT2 (291 +/- 1 mosmol/kg; P > 0.05 vs. C). Mean AP and CVP were similar between C and HT1, but both increased slightly in HT2. HR increased slightly but significantly during both HT1 and HT2 vs. C (P < 0.05). Sensitivity of baroreflex control of MSNA was significantly increased vs. C in HT1 [-7.59 +/- 0.97 (HT1) vs. -5.85 +/- 0.63 (C) arbitrary units (au).beat(-1).mmHg(-1); P < 0.01] but was not different in HT2 (-6.55 +/- 0.94 au.beat(-1).mmHg(-1)). We conclude that physiological changes in plasma osmolality significantly alter control of MSNA and HR in humans, and that this influence can be modified by CVP and AP.

Balance between cardiac output and sympathetic nerve activity in resting humans: role in arterial pressure regulation.

Large, reproducible interindividual differences exist in resting sympathetic nerve activity among normotensive humans with similar arterial pressures, resulting in a lack of correlation between muscle sympathetic nerve activity (MSNA) and arterial pressure among individuals. Although it is known that the arterial pressure is the main short-term determinant of MSNA in humans via the arterial baroreflex, the lack of correlation among individuals suggests that the level of arterial pressure is not the only important input in regulation of MSNA in humans. We studied the relationship between cardiac output (CO) and baroreflex control of sympathetic activity by measuring MSNA (peroneal microneurography), arterial pressure (arterial catheter), CO (acetylene uptake technique) and heart rate (HR; electrocardiogram) in 17 healthy young men during 20 min of supine rest. Across individuals, MSNA did not correlate with mean or diastolic blood pressure (r<0.01 for both), but displayed a significant negative correlation with CO (r=-0.71, P=0.001). To assess whether CO is related to arterial baroreflex control of MSNA, we constructed a baroreflex threshold diagram for each individual by plotting the percentage occurrence of a sympathetic burst against diastolic pressure. The mid-point of the diagram (T50) at which 50% of cardiac cycles are associated with bursts, was inversely related to CO (r=-0.75, P<0.001) and stroke volume (SV) (r=-0.57, P=0.015). We conclude that dynamic inputs from CO and SV are important in regulation of baroreflex control of MSNA in healthy, normotensive humans. This results in a balance between CO and sympathetically mediated vasoconstriction that may contribute importantly to normal regulation of arterial pressure in humans.