Evaluation of the Training Session in Elite Paralympic Powerlifting Athletes Based on Biomechanical and Thermal Indicators.

BACKGROUND: Paralympic powerlifting (PP) is performed on a bench press, aiming to lift as much weight as possible in a single repetition. PURPOSE: To evaluate thermal asymmetry and dynamic force parameters with 45 and 80% 1 Repetition Maximum (1 RM) in PP athletes. METHODS: Twelve elite PP male athletes were evaluated before and after a training session regarding skin temperature (thermography) and dynamic force indicators (Average Propulsive Velocity-MPV, Maximum Velocity-VMax, and Power). The training consisted of five series of five repetitions (5 × 5) with 80% 1 RM. The force indicators and dynamics before and after (45% 1 RM) were evaluated in series "1" and "5" with 80% 1 RM. RESULTS: The temperature did not present asymmetry, and there were differences between the moment before and after. In MPV, Vmax, and Power, with 45% 1 RM, there were differences both in asymmetry and in moments (p < 0.005). With 80% 1 RM, asymmetry was observed, but no differences between moments (p < 0.005). CONCLUSION: No thermal asymmetry was observed. There were reductions in MVP and VMax at 45 and 80% 1 RM but without significant differences between time points (before and after). However, there was asymmetry in the moments before and after within a safety standard, where Paralympic powerlifting was safe in terms of asymmetries.

Assessment of asymmetry at different intensities between conventional and paralympic powerlifting athletes.

Powerlifting competitions require consistent and symmetric lifting of heavy loads and maximal effort, in which, asymmetric lifting results in trial invalidation. Symmetry during this very high intensity movement is determinant to athletes' performance and success in competitions. This study aimed to compare the asymmetry between Conventional Powerlifting athletes (CP) and Paralympic (PP) athletes at intensities of 45 and 80% 1RM before and after a training session. Twenty-two male athletes (11 CP: 29.84 ± 4.21 and 11 PP: 30.81 ± 8.05 years old) participated in this study. Mean Propulsive Velocity (MPV), Maximum Velocity (Vmax) and Power during the concentric and eccentric phases were evaluated at 45%-1RM before and after a training session. For the intensity of 80%-1RM, MPV, Vmax and Power were measured in the first and last series (5 series of 5 repetitions: 5X5) of a training session. PP athletes demonstrated lower velocity and greater symmetry at 45%-1RM, but higher velocity and less asymmetry at 80%-1RM, when compared to CP. The data indicated that PP athletes tend to be slower at lower intensities, faster at higher intensities in absolute values, and have greater symmetry than CP.

The role of the microcirculation and integrative cardiovascular physiology in the pathogenesis of ICU-acquired weakness.

Skeletal muscle dysfunction after critical illness, defined as ICU-acquired weakness (ICU-AW), is a complex and multifactorial syndrome that contributes significantly to long-term morbidity and reduced quality of life for ICU survivors and caregivers. Historically, research in this field has focused on pathological changes within the muscle itself, without much consideration for their in vivo physiological environment. Skeletal muscle has the widest range of oxygen metabolism of any organ, and regulation of oxygen supply with tissue demand is a fundamental requirement for locomotion and muscle function. During exercise, this process is exquisitely controlled and coordinated by the cardiovascular, respiratory, and autonomic systems, and also within the skeletal muscle microcirculation and mitochondria as the terminal site of oxygen exchange and utilization. This review highlights the potential contribution of the microcirculation and integrative cardiovascular physiology to the pathogenesis of ICU-AW. An overview of skeletal muscle microvascular structure and function is provided, as well as our understanding of microvascular dysfunction during the acute phase of critical illness; whether microvascular dysfunction persists after ICU discharge is currently not known. Molecular mechanisms that regulate crosstalk between endothelial cells and myocytes are discussed, including the role of the microcirculation in skeletal muscle atrophy, oxidative stress, and satellite cell biology. The concept of integrated control of oxygen delivery and utilization during exercise is introduced, with evidence of physiological dysfunction throughout the oxygen delivery pathway - from mouth to mitochondria - causing reduced exercise capacity in patients with chronic disease (e.g., heart failure, COPD). We suggest that objective and perceived weakness after critical illness represents a physiological failure of oxygen supply-demand matching - both globally throughout the body and locally within skeletal muscle. Lastly, we highlight the value of standardized cardiopulmonary exercise testing protocols for evaluating fitness in ICU survivors, and the application of near-infrared spectroscopy for directly measuring skeletal muscle oxygenation, representing potential advancements in ICU-AW research and rehabilitation.

Population pharmacokinetics of apramycin from first-in-human plasma and urine data to support prediction of efficacious dose.

BACKGROUND: Apramycin is under development for human use as EBL-1003, a crystalline free base of apramycin, in face of increasing incidence of multidrug-resistant bacteria. Both toxicity and cross-resistance, commonly seen for other aminoglycosides, appear relatively low owing to its distinct chemical structure. OBJECTIVES: To perform a population pharmacokinetic (PPK) analysis and predict an efficacious dose based on data from a first-in-human Phase I trial. METHODS: The drug was administered intravenously over 30 min in five ascending-dose groups ranging from 0.3 to 30 mg/kg. Plasma and urine samples were collected from 30 healthy volunteers. PPK model development was performed stepwise and the final model was used for PTA analysis. RESULTS: A mammillary four-compartment PPK model, with linear elimination and a renal fractional excretion of 90%, described the data. Apramycin clearance was proportional to the absolute estimated glomerular filtration rate (eGFR). All fixed effect parameters were allometrically scaled to total body weight (TBW). Clearance and steady-state volume of distribution were estimated to 5.5 L/h and 16 L, respectively, for a typical individual with absolute eGFR of 124 mL/min and TBW of 70 kg. PTA analyses demonstrated that the anticipated efficacious dose (30 mg/kg daily, 30 min intravenous infusion) reaches a probability of 96.4% for a free AUC/MIC target of 40, given an MIC of 8 mg/L, in a virtual Phase II patient population with an absolute eGFR extrapolated to 80 mL/min. CONCLUSIONS: The results support further Phase II clinical trials with apramycin at an anticipated efficacious dose of 30 mg/kg once daily.

Integrated Dynamic Autonomic and Cardiovascular Regulation during Postural Transitions in Older Adults Living with Frailty: A Systematic Review Protocol.

Older adults often experience episodes of a sudden drop in blood pressure when standing, known as orthostatic hypotension (OH). OH is associated with an increased risk of life-threatening health problems, falls, and death. Although OH has been studied in older adults, the integrated dynamic autonomic and cardiovascular regulation during postural transitions in older adults with frailty remains scarce and poorly understood. The primary aim of this systematic review is to determine the association between how active (e.g., lie-to-stand) and passive (head-up tilt) postural transitions affect the dynamic integrated autonomic and cardiovascular regulatory responses, comparing older adults with different levels of frailty (non-frail, pre-frail, or frail). A second aim is to perform a meta-analysis to compare autonomic and cardiovascular responses during active postural transitions in non-frail, pre-frail, and frail older adults. The systematic review will be outlined according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. The meta-analysis will generate estimates of the comparative autonomic and cardiovascular responses after active postural transitions in adults who are non-frail, pre-frail, and frail. This systematic review will provide critical information on how integrated dynamic autonomic and cardiovascular regulation occurs during postural transitions in older adults with different frailty statuses.

A cross-sectional analysis of risk factors for cardiovascular diseases in older females: association between body fat distribution and physical fitness.

This study aimed to determine whether body fat distribution and physical fitness would be associated with risk factors for cardiovascular diseases (CVDs) in post-menopausal females. Android fat distribution were more likely to have altered total cholesterol (TC), high-density lipoprotein (HDL-C), triglycerides (TG), glycemic levels (GL) body fat percentage (%BF), and body mass index (BMI), and those with inadequate physical fitness showed clear alterations in TC, HDL-C, and TG. Gynoid fat distribution group fared better regarding CVD risk. In conclusion, adequate physical fitness demonstrates a protective factor against CVDs, with the greatest benefit to those with gynoid fat distribution.

Efeitos de um programa de exercícios remoto em ambiente domiciliar na capacidade funcional e a percepção da solidão em idosos socialmente isolados durante a covid-19 / Effects of remote home-based exercise program on functional capacity and perceived loneliness in older adults during COVID-19 lockdown

Resumo Objetivo Determinar os efeitos de um programa de exercício físico remoto realizado em ambiente domiciliar na capacidade funcional e percepção de solidão de idosos socialmente isolados, devido a pandemia da covid-19. Método Vinte e nove (29) idosos foram divididos aleatoriamente em dois grupos: (1) grupo controle (GC) e grupo de exercício em ambiente domiciliar (GEAD). A força muscular dos membros inferiores, a capacidade funcional e a percepção de solidão foram avaliadas no início (pré-teste), 4 semanas e 8 semanas (pós-teste). As avaliações consistiram no teste de sentar e levantar da cadeira (TSL), teste de velocidade de marcha (TVM), Timed Up and Go (TUG) e teste de percepção de solidão (TPS). Resultados O número de repetições durante o TSL foi estatisticamente diferente entre os grupos (GC vs. GEAD, p=0,006 e entre os momentos (Pré vs. 4S vs. 8S, p=0,043.). No teste de TUG, dentro do GC, o momento pré foi estatisticamente menor em relação ao momento de 8 semanas (p<0,021), indicando maior tempo para completar o TUG (pré 12,0±5,9 s vs. 8W 12,7±6,5 s). Essa mesma comparação não foi estatisticamente diferente dentro do GEAD. Não houve diferenças estatísticas no TVM e TPS entre os grupos e entre os momentos. Conclusão O programa de exercício domiciliar melhorou a capacidade funcional após 8 semanas de treinamento, mas a percepção de solidão e o teste de velocidade de marcha não foram afetados pelo programa de exercícios físico remoto em idosos isolados devido à pandemia de covid-19.

Abstract Objective to determine the effects of a simple home-based exercise program on functional capacity and perceived loneliness of older adults in lockdown due to the COVID-19 pandemic. Method Twenty-nine volunteers were randomly divided into two groups: (1) control group (CG); and (2) home-based exercise group (HBEG). Lower limb muscle strength, functional capacity, and perceived loneliness were assessed at baseline (pre-test), 4 weeks, and 8 weeks (post-test) using the Chair Standing Test (CST), Gait Speed Test (GST), Timed Up and Go test (TUG), and Perceived Loneliness Scale (PLS). Results The number of repetitions on the CST differed statistically between the groups (CG vs. HBEP, p=0.006) and among timepoints (Pre vs. 4W vs. 8W, p=0.043.). In the CG group, TUG test completion time was statistically lower at baseline than at 8 weeks (p=0.021) (pre 12.0±5.9 s vs. 8W 12.7±6.5 s). There was no statistical difference in TUG time in the HBEG. No statistical differences were found on the GST and PSL between groups or among timepoints. Conclusion The home-based exercise program improved general functional capacity after 8 weeks of training, but perceived loneliness and gait speed were unchanged in the older adults experiencing lockdown due to the COVID-19 pandemic.

Determination of somatotype and physical activity level in frailty older adults

Abstract Aim: To determine the somatotype profile and level of physical activity in older adults. Methods: Seventy-two older adults were divided into two groups: frail (F = 33) and non-frail (NF = 39). Frailty status was determined using the Tilburg Frailty Indicator (TFI), somatotype using the Heath and Carter method, and physical activity by the International Physical Activity Questionnaire (IPAQ). Results: Somatotype analysis showed a predominance of endomorphy (F = 6.54 ± 1.65 vs NF = 6.12 ± 2.07 p ≤ 0.350) followed by mesomorphy (F = 3.44 ± 1.62 vs NF = 3.15 ± 2.19, p ≤ 0.531) and ectomorphy (F = 0.82 ± 0.99 vs NF = 0.95 ± 0.86 p ≤ 0.163), but no significant differences were observed between groups. Regarding PA, twenty-eight participants (84.7%) of the F group were classified as sedentary and insufficiently active and twenty-one (53.8%) of NF were classified as active and very active. This difference in PA explains the higher total energy expenditure found in NF (median 1,087.43; IAQ = 3,954.30) when compared to F (median = 0.0; IAQ = 462.64 p ≤ 0.001). The frailty group presented a higher endomorphic component as well as lower levels of physical activity and energy expenditure. Conclusion: Endomorphy was the predominant somatotype in F and NF older adults, followed by mesomorphy and actomorphy this profile can affect activities of daily living, functional capacity, and independent living and be associated with chronic diseases.

Estimating minute ventilation and air pollution inhaled dose using heart rate, breath frequency, age, sex and forced vital capacity: A pooled-data analysis.

Air pollution inhaled dose is the product of pollutant concentration and minute ventilation ([Formula: see text]). Previous studies have parameterized the relationship between [Formula: see text] and variables such as heart rate (HR) and have observed substantial inter-subject variability. In this paper, we evaluate a method to estimate [Formula: see text] with easy-to-measure variables in an analysis of pooled-data from eight independent studies. We compiled a large diverse data set that is balanced with respect to age, sex and fitness level. We used linear mixed models to estimate [Formula: see text] with HR, breath frequency (fB), age, sex, height, and forced vital capacity (FVC) as predictors. FVC was estimated using the Global Lung Function Initiative method. We log-transformed the dependent and independent variables to produce a model in the form of a power function and assessed model performance using a ten-fold cross-validation procedure. The best performing model using HR as the only field-measured parameter was [Formula: see text] = e-9.59HR2.39age0.274sex-0.204FVC0.520 with HR in beats per minute, age in years, sex is 1 for males and 2 for females, FVC in liters, and a median(IQR) cross-validated percent error of 0.664(45.4)%. The best performing model overall was [Formula: see text] = e-8.57HR1.72fB0.611age0.298sex-0.206FVC0.614, where fB is breaths per minute, and a median(IQR) percent error of 1.20(37.9)%. The performance of these models is substantially better than any previously-published model when evaluated using this large pooled-data set. We did not observe an independent effect of height on [Formula: see text], nor an effect of race, though this may have been due to insufficient numbers of non-white participants. We did observe an effect of FVC such that these models over- or under-predict [Formula: see text] in persons whose measured FVC was substantially lower or higher than estimated FVC, respectively. Although additional measurements are necessary to confirm this finding regarding FVC, we recommend using measured FVC when possible.

Association Between Anaerobic Metabolic Demands During Simulated Brazilian Jiu-Jitsu Combat and Specific Jiu-Jitsu Anaerobic Performance Test.

Villar, R, Gillis, J, Santana, G, Pinheiro, DS, and Almeida, ALRA. Association between anaerobic metabolic demands during simulated Brazilian jiu-jitsu combat and specific jiu-jitsu anaerobic performance test. J Strength Cond Res 32(2): 432-440, 2018-The aims of this study were to design a specific Jiu-Jitsu anaerobic performance test (JJAPT) and investigate the relationship between blood lactate ([La]), heart rate (HR), and rating of perceived exertion (RPE) during simulated Brazilian Jiu-Jitsu combat (SBJJC) and JJAPT. Nine male elite Brazilian medium heavy weight athletes performed a 10-minute SBJJC and JJAPT that required performance of a common BJJ technique for 5 consecutive bouts of 1-minute with 45-second rest between bouts. [La] was measured by a lactate analyzer, HR by an HR monitor, and RPE using Borg's scale, and the number of repetitions of butterfly lifts (NBL) was recorded. During JJAPT, NBL decreased in the fourth and fifth bouts (p ≤ 0.05) with increases in [La], HR, and RPE (p ≤ 0.05), indicating that the JJAPT measured anaerobic performance. [La] during SBJJC was not different than [La] at the third and fourth bouts, but was significantly different than the fifth bout (p ≤ 0.05). [La] showed strong correlation between SBJJC and JJAPT for the third (r = 0.80, p ≤ 0.05), fourth (r = 0.83, p ≤ 0.05), and fifth (r = 0.82, p ≤ 0.05) bouts, but not between the HR and RPE. The JJAPT with 4 bouts presented the best combination of stimulus and highest correlation with SBJJC, supporting its use to assess anaerobic performance of BJJ athletes. These data will aid coaches and athletes to better understand the demands of their sport and may help to monitor adaptation in sport-specific performance across periodized training plans.

Sex differences in the oxygen delivery, extraction, and uptake during moderate-walking exercise transition.

Previous studies in children and older adults demonstrated faster oxygen uptake (V̇O2) kinetics in males compared with females, but young healthy adults have not been studied. We hypothesized that young men would have faster aerobic system dynamics in response to the onset of exercise than women. Interactions between oxygen supply and utilization were characterized by the dynamics of V̇O2, deoxyhemoglobin (HHb), tissue saturation index (TSI), cardiac output (Q̇), and calculated arteriovenous O2 difference (a-vO2diff) in women and men. Eighteen healthy active young women and men (9 of each sex) with similar aerobic fitness levels volunteered for this study. Participants performed an incremental cardiopulmonary treadmill exercise test and 3 moderate-intensity treadmill exercise tests (at 80% V̇O2 of gas exchange threshold). Data related to the moderate exercise were submitted to exponential data modelling to obtain parameters related to the aerobic system dynamics. The time constants of V̇O2, a-vO2diff, HHb, and TSI (30 ± 6, 29 ± 1, 16 ± 1, and 15 ± 2 s, respectively) in women were statistically (p < 0.05) faster than the time constants in men (42 ± 10, 49 ± 21, 19 ± 3, and 20 ± 4 s, respectively). Although Q̇ dynamics were not statistically different (p = 0.06) between groups, there was a trend to slower Q̇ dynamics in men corresponding with the slower V̇O2 kinetics. These results indicated that the peripheral and pulmonary oxygen extraction dynamics were remarkably faster in women. Thus, contrary to the hypothesis, V̇O2 dynamics measured at the mouth at the onset of submaximal treadmill walking were faster in women compared with men.

Vascular conductance and muscle blood flow during exercise are altered by inspired oxygen fraction and arterial perfusion pressure.

We tested the hypothesis during the combined challenges of altered inspired O2 fraction (FIO2) and posture changes at lower power output regardless of body position that the vascular conductance (VC) recruitment to the exercising muscle would not limit muscle perfusion and estimated O2 delivery (DO2est ). However, in head-down tilt at the higher power output exercise in hypoxia, the recruitment of VC would have a functional limitation which would restrict muscle blood flow (MBF) leading to a limitation in DO2est with consequent increases in metabolic stress. Ten healthy volunteers repeated plantar flexion contractions at 20% (low power output = LPO) and 30% (higher power output = HPO) of their maximal voluntary contraction in horizontal (HOR), 35° head-down-tilt (HDT) and 45° head-up-tilt (HUT). Popliteal diameter and muscle blood flow velocity were measured by ultrasound determining MBF. VC was estimated by dividing MBF flow by MPP, and DO2est was estimated by MBF times saturation. LPO HUT in hypoxia was associated with no changes in VC and MBF leading to reduced DO2est In LPO HDT under hypoxia, despite no apparent functional limitation in the VC recruitment, rise in MBF to maintain DO2est was associated with marked increase in muscle electromyographic activity, indicating greater metabolic stress. In HPO HDT under hypoxia, a functional limitation for the recruitment of VC constrained MBF and DO2est Elevated muscle electromyographic signal in HPO HDT under hypoxia was consistent with challenged aerobic metabolisms which contributed to a greater increase in the relative stress of the exercise challenge and advance the onset of muscle fatigue.

Outbreak Investigation of Plasmodium vivax Malaria in a Region of Guatemala Targeted for Malaria Elimination.

AbstractThe Department of Santa Rosa, Guatemala, is targeted for malaria elimination. However, compared with 2011, a 13-fold increase in cases was reported in 2012. To describe the epidemiology of malaria in Santa Rosa in the setting of the apparent outbreak, demographic and microscopic data from 2008 to 2013 were analyzed. In April 2012, a new surveillance strategy, funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, was introduced involving more active case detection, centralized microscopy, increased community engagement, and expanded vector control. Interviews with vector control personnel and site visits were conducted in June 2013. From 2008 to 2013, 337 cases of malaria were reported. The increase in cases occurred largely after the new surveillance strategy was implemented. Most (137/165; 83%) 2012 cases came from one town near a lake. Plasmodium vivax was the malaria species detected in all cases. Cases were detected where malaria was not previously reported. Monthly rainfall or/and temperature did not correlate with cases. Interviews with public health personnel suggested that the new funding, staffing, and strategy were responsible for improved quality of malaria detection and control and thus the increase in reported cases. Improvements in surveillance, case detection, and funding appear responsible for the temporary increase in cases, which thus may paradoxically indicate progress toward elimination.

Estimating oxygen uptake and energy expenditure during treadmill walking by neural network analysis of easy-to-obtain inputs.

The study of oxygen uptake (V̇o2) dynamics during walking exercise transitions adds valuable information regarding fitness. However, direct V̇o2 measurements are not practical for general population under realistic settings. Devices to measure V̇o2 are associated with elevated cost, uncomfortable use of a mask, need of trained technicians, and impossibility of long-term data collection. The objective of this study was to predict the V̇o2 dynamics from heart rate and inputs from the treadmill ergometer by a novel artificial neural network approach. To accomplish this, 10 healthy young participants performed one incremental and three moderate constant work rate treadmill walking exercises. The speed and grade used for the moderate-intensity protocol was related to 80% of the V̇o2 response at the gas exchange threshold estimated during the incremental exercise. The measured V̇o2 was used to train an artificial neural network to create an algorithm able to predict the V̇o2 based on easy-to-obtain inputs. The dynamics of the V̇o2 response during exercise transition were evaluated by exponential modeling. Within each participant, the predicted V̇o2 was strongly correlated to the measured V̇o2 ( = 0.97 ± 0.0) and presented a low bias (~0.2%), enabling the characterization of the V̇o2 dynamics during treadmill walking exercise. The proposed algorithm could be incorporated into smart devices and fitness equipment, making them suitable for tracking changes in aerobic fitness and physical health beyond the infrequent monitoring of patients during clinical interventions and rehabilitation programs.

Investigating the impact of passive external lower limb compression on central and peripheral hemodynamics during exercise.

PURPOSE: The objective of this study was to assess the effectiveness of graduated compression socks (GCS) on enhancing muscle blood flow and oxygenation during exercise and recovery in healthy subjects. METHODS: Twelve healthy volunteers completed a protocol involving baseline, exercise, and recovery periods with and without GCS. Each test was repeated twice to assess repeatability of the results. The applied sock pressure was measured prior to experimentation using a custom pressure sensing system, and modified as necessary using tensor bandages to control the applied load. During each of the experimental phases, blood velocity in the popliteal artery, calf muscle tissue oxygenation, muscle activity, heart rate, blood pressure, cardiac output, and applied pressure from the sock were measured. Popliteal artery diameter was measured during baseline and recovery periods. RESULTS: The GCS significantly reduced deoxyhemoglobin (HHb) in the leg during baseline (HHb, p = 0.001) and total blood volume and HHb in the leg during exercise (total hemoglobin, p = 0.01; HHb, p = 0.02). However, there were no differences in leg muscle blood flow velocity or any other variables with and without GCS at baseline, exercise, or recovery. Interestingly, it was found that the local applied sock pressure was very sensitive to the sock application process and, furthermore, the pressure varied considerably during exercise. CONCLUSIONS: No significant changes were observed in measures reflecting oxygen delivery for healthy subjects using GCS during exercise and recovery. Applied sock pressure was carefully controlled, thus eliminating the sock application process as a variable.

Validation of the Hexoskin wearable vest during lying, sitting, standing, and walking activities.

We tested the validity of the Hexoskin wearable vest to monitor heart rate (HR), breathing rate (BR), tidal volume (VT), minute ventilation, and hip motion intensity (HMI) in comparison with laboratory standard devices during lying, sitting, standing, and walking. Twenty healthy young volunteers participated in this study. First, participants walked 6 min on a treadmill at speeds of 1, 3, and 4.5 km/h followed by increasing treadmill grades until 80% of their predicted maximal heart rate. Second, lying, sitting, and standing tasks were performed (5 min each) followed by 6 min of treadmill walking at 80% of their ventilatory threshold. Analysis of each individual's mean values under each resting or exercise condition by the 2 measurement systems revealed low coefficient of variation and high intraclass correlation values for HR, BR, and HMI. The Bland-Altman results from HR, BR, and HMI indicated no deviation of the mean value from zero and relatively small variability about the mean. VT and minute ventilation were provided in arbitrary units by the Hexoskin device; however, relative magnitude of change from Hexoskin closely tracked the laboratory standard method. Hexoskin presented low variability, good agreement, and consistency. The Hexoskin wearable vest was a valid and consistent tool to monitor activities typical of daily living such as different body positions (lying, sitting, and standing) and various walking speeds.

Prior head-down tilt does not impair the cerebrovascular response to head-up tilt.

The hypothesis that cerebrovascular autoregulation was not impaired during head-up tilt (HUT) that followed brief exposures to varying degrees of prior head-down tilt (HDT) was tested in 10 healthy young men and women. Cerebral mean flow velocity (MFV) and cardiovascular responses were measured in transitions to a 60-s period of 75° HUT that followed supine rest (control) or 15 s HDT at -10°, -25°, and -55°. During HDT, heart rate (HR) was reduced for -25° and -55°, and cardiac output was lower at -55° HDT. MFV increased during -10° HDT, but not in the other conditions even though blood pressure at the middle cerebral artery (BPMCA) increased. On the transition to HUT, HR increased only for -55° condition, but stroke volume and cardiac output transiently increased for -25° and -55°. Total peripheral resistance index decreased in proportion to the magnitude of HDT and recovered over the first 20 s of HUT. MFV was significantly less in all HDT conditions compared with the control in the first 5-s period of HUT, but it recovered quickly. An autoregulation correction index derived from MFV recovery relative to BPMCA decline revealed a delay in the first 5 s for prior HDT compared with control but then a rapid increase to briefly exceed control after -55° HDT. This study showed that cerebrovascular autoregulation is modified by but not impaired by brief HDT prior to HUT and that cerebral MFV recovered quickly and more rapidly than arterial blood pressure to protect against cerebral hypoperfusion and potential syncope.

Comparative effects of sodium channel blockers in short term rat whole embryo culture.

This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the l-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the l-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB>bupivacaine>AZA>lidocaine>nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart.

Lower limb vascular conductance and resting popliteal blood flow during head-up and head-down postural challenges.

This study hypothesized that central and local reflex mechanisms affecting vascular conductance (VC) through the popliteal artery compensated for the reduction in muscle perfusion pressure (MPP) to maintain popliteal blood flow (PBF) during head-down tilt (35˚ HDT), but not in head-up tilt (45˚ HUT). Resting measurements were made on 15 healthy men in prone position to facilitate the access to the popliteal artery, on two separate days in random order during horizontal (HOR), HDT or HUT. In each body position, the body was supported, and the ankles were maintained in relaxed state so that there was no muscle tension, as with normal standing. Popliteal blood flow velocity and popliteal arterial diameter were measured by ultrasound, and PBF was calculated. MPP was corrected to mid-calf from measured finger cuff pressure, and VC was estimated by dividing PBF by MPP. The MPP in HDT (48 ± 2 mmHg) was ~100mmHg less than in HUT (145 ± 2 mmHg). PBF was similar between HOR (51 ± 18 ml( ) min(-1) ) and HDT (47 ± 13 ml min(-1) ), but was lower in HUT (30 ± 9 ml min(-1) ). VC was different between HDT (1·0 ± 0·3 ml min(-1)  mmHg(-1) ), HOR (0·6 ± 0·2 ml min(-1)  mmHg(-1) ) and HUT (0·2 ± 0·1 ml min(-1)  mmHg(-1) ). In conclusion, the interactions of central and local regulatory mechanisms resulted in a disproportionate reduction of VC during HUT lowering PBF even though MPP was higher, while in HDT, increased VC contributed to maintain PBF at the same level as the HOR control condition.