Respiratory muscle performance with stretch-shortening cycle manoeuvres: maximal inspiratory pressure-flow curves

AIM: To test the hypothesis that the maximal inspiratory muscle (IM) performance, as assessed by the maximal IM pressure-flow relationship, is enhanced with the stretch-shortening cycle (SSC). METHODS: Maximal inspiratory flow-pressure curves were measured in 12 healthy volunteers (35 +/- 6 years) during maximal single efforts through a range of graded resistors (4-, 6-, and 8-mm diameter orifices), against an occluded airway, and with a minimal load (wide-open resistor). Maximal inspiratory efforts were initiated at a volume near residual lung volume (RV). The subjects exhaled to RV using slow (S) or fast (F) manoeuvres. With the S manoeuvre, they exhaled slowly to RV and held the breath at RV for about 4 s prior to maximal inspiration. With the F manoeuvre, they exhaled rapidly to RV and immediately inhaled maximally without a post-expiratory hold; a strategy designed to enhance inspiratory pressure via the SSC. RESULTS: The maximal inspiratory pressure-flow relationship was linear with the S and F manoeuvres (r2 = 0.88 for S and r2 = 0.88 for F manoeuvre, P < 0.0005 in all subjects). With the F manoeuvre, the pressure-flow relationship shifted to the right in a parallel fashion and the calculated maximal power increased by approximately 10% (P < 0.05) over that calculated with the S manoeuvre. CONCLUSION: The maximal inspiratory pressure-flow capacity can be enhanced with SSC manoeuvres in a manner analogous to increases in the force-velocity relationship with SSC reported for skeletal muscles.     

Left ventricular pressure–volume relationships during normal growth and development in the adult rat – studies in 8‐ and 50‐week‐old male Wistar rats

Aims: Left ventricular (LV) pressure–volume relations provide relatively load‐independent indexes of systolic and diastolic LV function, but few data are available on pressure–volume relations during growth and development in the normal adult heart. Furthermore, to quantify intrinsic ventricular function the indexes should be normalized for heart weight. However, in many studies the indexes are reported in absolute terms, or body weight‐correction is used as a surrogate for heart weight‐correction. Methods: We determined pressure–volume relations in young (8‐week‐old, n = 13) and middle‐aged (50‐week‐old, n = 19) male Wistar rats in relation to their heart and body weights. The animals were anaesthetized and a 2F pressure‐conductance catheter was introduced into the LV to measure pressure–volume relations. Results: Heart and body weights were significantly higher in the 50‐week‐old rats, whereas the heart‐to‐body weight ratio was significantly lower (2.74 ± 0.32 vs. 4.41 ± 0.37 mg g^?1, P < 0.001). Intrinsic systolic function, quantified by the slopes of the end‐systolic pressure–volume relation (E_ES), the dP/dt_MAX vs. end‐diastolic volume relation (S‐dP), and the preload recruitable stroke work relation (PRSW), normalized for heart weight, was slightly decreased in the 50‐week‐old rats (S‐dP: ?6%, P < 0.004; PRSW: ?3%, P < 0.06). Heart weight‐corrected diastolic indexes were not significant different. The absolute indexes qualitatively showed the same results, but body‐weight corrected pressure–volume indexes showed improved systolic function and significantly depressed diastolic function. Conclusions: Intrinsic systolic function slightly decreases from the juvenile to the middle‐aged period in normal male Wistar rats. Furthermore, correction of pressure–volume indexes for body weight is not an adequate surrogate for heart weight‐correction in these animals.     

Maximal strength and power characteristics in isometric and dynamic actions of the upper and lower extremities in middle-aged and older men

Muscle cross-sectional area of the quadriceps femoris (CSA_QF), maximal isometric strength (handgrip test and unilateral knee extension/flexion), the shape of isometric force–time curves, and power–load curves during concentric and stretch–shortening cycle (SSC) actions with loads ranging from 15 to 70% of one repetition maximum half-squat (1RM_HS) and bench-press (1RM_BP) were examined in 26 middle-aged men in the 40-year-old (M40) (mean age 42, range 35–46) and 21 elderly men in the 65-year-old age group (M65) (mean age 65, range 60–74). Maximal bilateral concentric (1RM_HS and 1RM_BP), unilateral knee extension (isometric; MIF_KE and concentric; 1RM_KE) strength and muscle CSA in M65 were lower (P < 0.001) than in M40. The individual values of the CSA_QF correlated with the individual values of maximal concentric 1RM_HS, 1RM_KE and MIF_KE in M65, while the corresponding correlations were lower in M40. The maximal MIF_KE value per CSA of 4.54 ± 0.7 N m cm^–2 in M40 was greater (P < 0.05–0.01) than that of 4.02 ± 0.7 N m cm^–2 recorded in M65. The maximal rate of force development of the knee extensors and flexors in M65 was lower (P < 0.01–0.001) and the heights in squat and counter-movement jumps as much as 27–29% lower (P < 0.001) than those recorded in M40. M65 showed lower (P < 0.001) concentric power values for both upper and lower extremity performances than those recorded for M40. Maximal power output was maximized at the 30–45% loads for the upper extremity and at the 60–70% loads for the lower extremity extensors in both age groups. Muscle activation of the antagonists was significantly higher (P < 0.01–0.001) during the isometric and dynamic knee extension actions in M65 than in M40. The present results support a general concept that parallel declines in muscle mass and maximal strength take place with increasing age, although loss of strength may vary in both lower and upper extremity muscles in relation to the type of action and that ageing may also lead to a decrease in voluntary neural drive to the muscles. Explosive strength and power seem to decrease with increasing age even more than maximal isometric strength in both actions but power was maximized at the 30–45% loads for the upper and at the 60–70% loads for the lower extremity action in both age groups. High antagonist muscle activity may limit the full movement efficiency depending on the type of muscle action, testing conditions and the velocity and/or the time duration of the action, especially in the elderly.     

Effects of muscle group recruitment on sniff transdiaphragmatic pressure and its components

Measuring maximal sniff pressures is an easy way of assessing inspiratory muscle strength. During a static manoeuvre, the pattern of inspiratory muscle recruitment during a sniff can vary from one individual to another. We therefore assessed how voluntarily changing muscle recruitment would affect sniff oesophageal, gastric and transdiaphragmatic pressures (Pes,sn, Pga,sn and Pdi,sn, respectively). Ten normal subjects (age 27–38 years) performed natural sniff manoeuvres ("nat"), and preferentially diaphragmatic ("dia") or extradiaphragmatic ("extradia") sniff manoeuvres, after having learnt to dissociate between the inspiratory muscle groups. Abdominal displacements were monitored using a belt-mounted strain gauge. Natural patterns of muscle recruitment varied among subjects. On average, Pes,sn,nat was [median (range)] 81 (21–105) cmH₂O. All of the subjects were able to modify inspiratory muscle recruitment voluntarily. Pes,sn was not significantly affected by the type of manoeuvre performed, as opposed to Pdi,sn, which, as expected, increased with both the diaphragmatic and extradiaphragmatic manoeuvres [Pdi,sn,dia 132 (99–157) cmH₂O, Pdi,sn,extradia 96 (50–146) cmH₂O, P<0.05]. Whatever the manoeuvre, there was no correlation between Pes and Pdi, but Pga and Pdi were correlated during both the diaphragmatic (r=0.82, P<0.05) and the extradiaphragmatic manoeuvre (r=0.70, P< 0.05). Pes,sn may have limitations as an index of diaphragm function, but by showing its independence from inspiratory muscle recruitment, this study contributes to its validation as a robust index of global inspiratory muscle strength that is particularly well suited for follow-up studies. This should extend to Pes,sn substitutes measured at the airway opening. Electronic Publication     

Changes in maximal performance of inspiratory and skeletal muscles during and after the 7.1-MPa Hydra 10 record human dive

 During the 7.1-MPa hydrogen-helium-oxygen record human dive, we tested the hypothesis that the increased ambient pressure would alter the maximal muscle performance, specifically that breathing dense gas would lead to fatigue of the respiratory muscle. A group of hand muscles (adductor pollicis, AP) and the inspiratory muscles (IM) were studied in three professional divers. Maximal voluntary contractions (MVC) of AP and maximal inspiratory pressure (P _imax) generated by IM were measured prior to the dive, during compression and decompression, and then 1 and 2 months after the dive. The decrease in MVC (−22%) was significant at 3.1 MPa, i.e. at the beginning of the introduction of hydrogen into the breathing mixture, whereas P _imax fell progressively during the dive and decompression (maximal ΔP _imax = −55%), a significant reduction still being measured 1 month after the dive. The altered IM function was attributed to the consequences of long-term ventilatory loading, a condition associated with breathing a dense gas. The transient decrease in MVC of the skeletal muscle would indicate a possible effect of the hyperbaric environment, possibly the high partial pressure of hydrogen, on neuromuscular drive. Accepted: 16 September 1999     

Interaction between the renin–angiotensin system and insulin-like growth factor I in aorto-caval fistula-induced cardiac hypertrophy in rats

The effects of angiotensin converting enzyme inhibition and angiotensin II receptor blockade on the development of cardiac hypertrophy and myocardial insulin-like growth factor I (IGF-I) in volume overload were studied in male Wistar rats with aorto-caval fistulas (ACF). Rats were treated with ramipril (RAM, 3 mg kg^–1 day^–1) for 4–20 days or losartan (LOS, 10 mg kg^–1 day^–1) for 2–7 days. Myocardial IGF-I and IGF-I receptor (IGF-I-R) mRNA were determined by solution hybridization. ACF caused hypertrophy of left (LV) and right ventricles (RV). Hypertrophy appeared on day 2 and reached maximal values of +60% in LV and +75% in RV at day 12. Systolic blood pressure was initially reduced 15% but recovered by day 12. RAM abolished the recovery of blood pressure. Furthermore, RAM attenuated RV hypertrophy by 17% on day 7 and on day 20, RV weights were close to values found in controls. Beginning on day 9, RAM reduced LV weight back to control levels in parallel to blood pressure. In contrast, LOS affected neither RV nor LV hypertrophy. RV IGF-I mRNA increased 60–100% on day 7 alone in RV in ACF. RAM potentiated the increase in RV IGF-I to +400% and induced an increase in RV IGF-I-R mRNA on day 7 (+90%) in ACF. LOS did not affect RV IGF-I. Development of cardiac hypertrophy in ACF seemed independent of angiotensin II. RV hypertrophy was associated with activation of IGF-I independent of the renin–angiotensin system. IGF-I was further potentiated when development of hypertrophy was attenuated, possibly indicative of a greater urge for compensational growth in a relatively thinner and more volume-distended chamber.     

Acute effects of pulmonary artery banding in sheep on right ventricle pressure–volume relations: relevance to the arterial switch operation

The first stage of the two‐stage arterial switch operation (ASO) for transposition of the great arteries (TGA) is associated with depressed ventricular function and an unstable immediate post‐operative course. It is unclear if this is because of the acute increase in afterload of the thin‐walled, low‐pressure ventricle by pulmonary artery banding (PAB). To determine the acute effects of afterload increase on the contractile function of thin‐walled ventricles, we studied the right ventricular pressure–volume relations of seven sheep before and 30 min after PAB using combined pressure–conductance catheters during inflow reduction. Load independent indices of systolic and diastolic performance were derived from these relations. Pulmonary artery banding increased the mean ratio between right and left ventricular systolic pressure from 0.34 ± 0.05 to 0.64 ± 0.10, P < 0.05 (mean ± SD). There were no significant changes in heart rate and end‐systolic volume after banding although there was an incremental trend in the end‐diastolic volume and stroke volume. Right ventricular output (530 ± 163–713 ± 295 mL min^–1, P < 0.05), slope of the end‐systolic pressure–volume relation (ESPVR) (3.7 ± 2.8–10.0 ± 4.8 mmHg mL^–1, P < 0.05) and slope of the pre‐load recruitable stroke work (PRSW) relation (9.6 ± 1.8–15.0 ± 3.1 mmHg, P < 0.05) were significantly increased indicating improved contractile state after banding. The diastolic function curve was unchanged after banding although the right ventricle (RV) was operating at a larger end‐diastolic volume. Hence, the RV of sheep responded to acute pressure overload by demonstrating enhanced contractility and evidence of the Frank–Starling mechanism without associated change in right ventricular diastolic performance.     

Comprehensive MRI for the detection of subtle alterations in diastolic cardiac function in apoE/LDLR–/– mice with advanced atherosclerosis

ApoE/LDLR^–/– mice represent a reliable model of atherosclerosis. However, it is not clear whether cardiac performance is impaired in this murine model of atherosclerosis. Here, we used MRI to characterize cardiac performance in vivo in apoE/LDLR^–/– mice with advanced atherosclerosis. Six‐month‐old apoE/LDLR^–/– mice and age‐matched C57BL/6J mice (control) were examined using highly time‐resolved cine‐MRI [whole‐chamber left ventricle (LV) imaging] and MR tagging (three slices: basal, mid‐cavity and apical). Global and regional measures of cardiac function included LV volumes, kinetics, time‐dependent parameters, strains and rotations. Histological analysis was performed using OMSB (orceine with Martius, Scarlet and Blue) and ORO (oil red‐O) staining to demonstrate the presence of advanced coronary atherosclerosis. MR‐tagging‐based strain analysis in apoE/LDLR^–/– mice revealed an increased frequency of radial and circumferential systolic stretch (25% and 50% of segments, respectively, p ≤ 0.012), increased radial post‐systolic strain index (45% of segments, p = 0.009) and decreased LV untwisting rate (?30.3° (11.6°)/cycle, p = 0.004) when compared with control mice. Maximal strains and LV twist were unchanged. Most of the cine‐MRI‐based LV functional and anatomical parameters also remained unchanged in apoE/LDLR^–/–mice, with only a lower filling rate, longer filling time, shorter isovolumetric contraction time and slower heart rate observed in comparison with control mice. The coronary arteries displayed severe atherosclerosis, as evidenced by histological analysis. Using comprehensive MRI methods, we have demonstrated that, despite severe coronary atherosclerosis in six‐month‐old apoE/LDLR^–/– mice, cardiac performance including global parameters, twist and strains, was well preserved. Only subtle diastolic alterations, possibly of ischemic background, were uncovered. Copyright © 2016 John Wiley & Sons, Ltd.     

Effect of specific inspiratory muscle warm-up on intense intermittent run to exhaustion

The effects of inspiratory muscle (IM) warm-up on the maximum dynamic IM function and the maximum repetitions of 20-m shuttle run (Ex) in the Yo-Yo intermittent recovery test were examined. Ten men were recruited to perform identical IM function test and exercise test in three different trials randomly. The control trial was without IM warm-up while the placebo and experimental trials were with IM warm-up by performing two sets of 30 breaths with inspiratory pressure-threshold load equivalent to 15% (IMW_P) and 40% (IMW) maximum inspiratory mouth pressure, respectively. In IMW, maximum dynamic IM functions including the maximal inspiratory pressure at zero flow (P ₀) and maximal rate of P ₀ development (MRPD) were increased compared with control values (P<0.05). The Ex was also augmented [mean (SD)] [19.5% (12.6)] while the slope of the linear relationship of the increase in rating of perceived breathlessness for every 4th exercise interval (RPB/4i) was reduced (P<0.05). In IMW_P, although increase in Ex and reduction in RPB/4i were occurred concomitantly in some subjects, the differences in Ex, RPB/4i and dynamic IM functions between control and IMW_P trials were not statistically significant. For the changes (Δ) in parameters in IMW and IMW_P (n=20), negative correlations were found between Δ RPB/4i and Δ Ex (r=−0.92), ΔP ₀ and Δ RPB/4i (r=−0.48), and Δ MRPD and Δ RPB/4i (r=−0.54). Such findings suggested that the specific IM warm-up in IMW may entail reduction in breathlessness sensation, partly attributable to the enhancement of dynamic IM functions, in subsequent exhaustive intermittent run and, in turn, improve the exercise tolerance.     

Inspiratory muscle adaptations following pressure or flow training in humans

Skeletal muscle adapts differently to training with high forces or with high velocities. The effects of these disparate training protocols on the inspiratory muscles were investigated in ten healthy volunteers. Five subjects trained using high force (pressure) loads (pressure trainers) and five trained using high velocity (flow) loads (flow trainers). Pressure training entailed performing 30 maximal static inspiratory efforts against a closed airway. Flow training entailed performing 30 sets of three maximal dynamic inspiratory efforts against a minimal resistance. Training was supervised and carried out 5 days a week for 6 weeks. Inspiratory flow rates and oesophageal pressure-time curves were measured before and after training. Peak inspiratory pressures during maximal static and dynamic efforts and peak flows during the maximal dynamic efforts were calculated. The time-to-peak pressure and rate of rise in peak pressure during maximal static and dynamic manoeuvres were also calculated before and following training. Maximal static pressure increased in the pressure training group and maximal dynamic pressure increased in the flow training group. Both groups increased the rate of pressure production (dP/dt) during their respective maximal efforts. The post-training decrease in time-to-peak pressure was proportionately greater in the flow trainers than in the pressure trainers. The differences in time-to-peak pressure between the two groups were consistent with the different effects of force and velocity training on the time-to-peak tension of skeletal muscle.     

Behaviour of vastus lateralis muscle–tendon during high intensity SSC exercises in vivo

Aims: The interaction between fascicle and tendinous tissue of human vastus lateralis muscle was investigated during varying intensity stretch–shortening cycle (SSC) jumps performed on a sledge apparatus. Methods: Eight subjects performed single leg squat (SJ) and drop jumps (DJ) from a constant dropping height but to different rebound heights. The fascicle length of the vastus lateralis muscle (VL) was determined from real‐time ultrasonography during the movement. Tendon length changes were calculated by subtracting the horizontal part of the fascicle length from the muscle–tendon unit (MTU) length. Simultaneously, kinematic, kinetic and electromyographic data were recorded from leg muscles. In addition, the in vivo patella tendon force was measured from one subject during the trials. Results: In all DJs, where MTU was stretched prior to shortening, the fascicle and tendinous tissue of the VL also underwent a SSC. The fascicle lengths decreased and the recoil of tendinous tissue increased with increased rebound intensities (P < 0.05). The force–velocity curves obtained from the MTU showed the expected force–velocity relationship for SSC activities, demonstrating performance enhancement. However, the increased MTU power during the shortening phase of the movement was due primarily to the enhancement of the tendon compartment. Conclusion: The results of this study show that, at higher rebound intensities, the fascicle is controlled during the braking phase in a distinct manner so that the effective recoil of the tendon is possible during the final push‐off phase. In addition, the results suggest that the behaviour of fascicle length change depends on the muscle in question in addition to the movement intensity.     

Maximal dynamic expiratory pressures with fast and slow inspirations

Maximal dynamic expiratory pressures are higher when forced expiration is preceded by a fast inspiration to total lung capacity (TLC) than when preceded by a slow inspiration and a few seconds pause at TLC. We hypothesized that these pressure differences are due to the stretch-shorten cycle (SSC), which refers to enhancement of muscle force when a concentric muscle contraction is immediately preceded by an eccentric contraction. Seven volunteers [36 (2) years; mean (SEM)] performed maximal forced expirations against minimal resistance with fast (F) or slow (S) maneuvers. F maneuvers consisted of a fast inspiration to TLC followed immediately by a fast expiration, whereas S consisted of a slow inspiration to TLC and a 4- to 5-s pause at TLC prior to forced expiration. We measured esophageal pressure (P _es), peak expiratory flow rate (PEFR), and the EMG activity of the transversus abdominis (Tr) by means of intramuscular fine-wire electrodes. The subjects performed several runs of each maneuver in a random order, and runs with the greatest expiratory P _es were analyzed. In comparison with S, F yielded greater P _es [182 (15) versus 167 (15) cmH₂O; P=0.003)] but similar PEFR [9.8 (0.7) versus 9.6 (0.7) l/s, P>0.05] and EMG activity of the Tr during forced expiration [221 (31) versus 208 (34) a.u., P>0.05]. Further analysis revealed significant EMG activity of Tr during end-inspiration (eccentric contraction) with F maneuvers only [73 (22) versus 32 (17) a.u., P<0.05]. We conclude that the ability of expiratory muscles to generate greater P _es with F maneuvers is related to the sequence of an eccentric contraction, which is followed immediately by concentric contraction in a manner analogous to SSC described in skeletal muscles. Electronic Publication     

Quantification of α‐subunit isoforms of Na,K‐ATPase in rat resistance vessels

Aim: Rat mesenteric resistance vessels (RV) were characterized with respect to concentration of individual α‐subunit isoforms of Na,K‐ATPase. Methods: Total vessel homogenates were used to avoid any loss or subfractionation of membranes. They were applied to sodium dodecyl sulphate gels and, for calibration, in parallel lanes were run purified rat Na,K‐ATPase preparations with known isoform distribution and content. The capacity per mg protein for Na⁺‐dependent ³²P‐phosphorylation of Na,K‐ATPase isolated from rat kidney was used for α₁ calibration and that for high‐affinity (³H)ouabain binding of Na,K‐ATPase isolated from rat brain was used for (α₂ + α₃) calibration. Western blots containing homogenate proteins and reference enzyme were incubated with isoform‐specific antibodies and radiolabelled secondary antibodies. The signals from adjacent α spots were used for qualitative and quantitative characterization of rat vessels. Results: A concentration of 100.7 ± 14.4 pmol (n = 11) per g wet weight of the α₁‐isoform containing Na,K‐ATPase was found in RV from 12–14‐week rats. A much lower and more unreliable content of α₂‐ and α₃‐isoforms was found. These ouabain‐sensitive isoforms seem to represent a maximum of 5–10% each compared with the ouabain‐insensitive rat α₁‐isoform. Conclusions: The isoform pattern in RV, in which the isoform with high/intermediate Na⁺‐affinity is the absolutely dominating one representing nearly all sodium pumps in this tissue, is very different from that seen in rat skeletal muscles. Due to the high content of the ouabain‐insensitive α₁‐isoform in rat RV this species would seem a less relevant model in studies addressing a role of cardiac glycosides and putative endogenous ouabain‐like factors in hypertension.     

Investigation into the Kinetics of n‐Pentyl Methacrylate Radical Polymerization

The precise knowledge of rate coefficients is of key importance for the understanding and the application of radical polymerization processes. Propagation rate coefficients, k_p, of n‐pentyl methacrylate (PnMA) radical polymerization are measured in bulk and partly in toluene solution over an extended temperature range via pulsed laser polymerization (PLP) in conjunction with size‐exclusion chromatography (PLP–SEC). Rate coefficients, k_t^i,i, for termination of two radicals of chain length i are determined as a function of chain length by single‐pulse PLP in conjunction with electron paramagnetic resonance spectroscopy (SP–PLP–EPR). The as‐obtained data that allow for modeling PnMA polymerization kinetics and product properties at moderate degrees of monomer conversion are compared with reported data for several other alkyl methacrylates. A distinct family behavior of this group of monomers is seen.     

Nerve growth factor increases airway responses and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea‐pig model

There is a growing body of evidence supporting the idea that nerve growth factor (NGF) may be involved in the development of asthma‐associated symptoms, such as airway hyper‐responsiveness. Increased levels of NGF have recently been described in serum and in the airways of asthmatics. We have examined whether exhaled nitric oxide (NO) levels might be altered during the increased airway responses upon NGF treatment in guinea‐pigs in vivo. Intravenous (i.v.) administration of histamine normally elicits a rapid peak in insufflation pressure (IP) and in exhaled NO, followed by a period of decreased concentrations of exhaled NO. Anaesthetized guinea‐pigs were pre‐treated intravenously with either saline, 4 or 80 ng kg^–1 NGF 30 min before i.v. challenge with 16 μg kg^–1 histamine. At 80 ng kg^–1 NGF significantly enhanced the airway obstruction caused by histamine, whereas the peak acute increase in exhaled NO was not enhanced. Following the increase, came a rapid drop, an effect enforced in the NGF treated animals. Subsequently, the time to return to 90% of resting exhaled NO was increased, from 12 min in saline‐treated animals to 48 min in NGF‐treated animals. Our data confirm that NGF can enhance airway responses to histamine. Moreover, our study shows a decrease in exhaled NO following a histamine challenge, an effect enhanced by NGF. A reduced ability to release exhaled NO may be a mechanism for increased airway responses during elevated NGF levels. The interaction between NGF and airway NO formation, and its relation to airway responses, merit further investigation.     

19 F MRSI of capecitabine in the liver at 7 T using broadband transmit–receive antennas and dual‐band RF pulses

Capecitabine (Cap) is an often prescribed chemotherapeutic agent, successfully used to cure some patients from cancer or reduce tumor burden for palliative care. However, the efficacy of the drug is limited, it is not known in advance who will respond to the drug and it can come with severe toxicity. ¹⁹ F Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Spectroscopic Imaging (MRSI) have been used to non‐invasively study Cap metabolism in vivo to find a marker for personalized treatment. In vivo detection, however, is hampered by low concentrations and the use of radiofrequency (RF) surface coils limiting spatial coverage. In this work, the use of a 7T MR system with radiative multi‐channel transmit–receive antennas was investigated with the aim of maximizing the sensitivity and spatial coverage of ¹⁹ F detection protocols. The antennas were broadband optimized to facilitate both the ¹H (298 MHz) and ¹⁹ F (280 MHz) frequencies for accurate shimming, imaging and signal combination. B₁⁺ simulations, phantom and noise measurements showed that more than 90% of the theoretical maximum sensitivity could be obtained when using B₁⁺ and B₁^? information provided at the ¹H frequency for the optimization of B₁⁺ and B₁^? at the ¹⁹ F frequency. Furthermore, to overcome the limits in maximum available RF power, whilst ensuring simultaneous excitation of all detectable conversion products of Cap, a dual‐band RF pulse was designed and evaluated. Finally, ¹⁹ F MRS(I) measurements were performed to detect ¹⁹ F metabolites in vitro and in vivo. In two patients, at 10 h (patient 1) and 1 h (patient 2) after Cap intake, ¹⁹ F metabolites were detected in the liver and the surrounding organs, illustrating the potential of the set‐up for in vivo detection of metabolic rates and drug distribution in the body. Copyright © 2015 John Wiley & Sons, Ltd.     

Power absorption and production during slow,large-amplitude stretch-shorten cycle motions

The purpose of this study was to determine the important predictors of power absorption and power production during slow, large-amplitude stretch-shorten cycle (SSC) motions. The relationship between power absorption (mean eccentric power output) and production (mean concentric power output) across different inertial loads was also investigated. Fifty-four subjects with a sporting background performed concentric (CBP) and rebound bench-presses (RBP) at 40% and 80% of their one-repetition maximum (1RM). The relationship between kinematic and kinetic variables and mean eccentric power and RBP mean power output was determined using correlation and multiple regression analysis. Maximal strength was found to be the best single predictor of power absorption, explaining between 44.2% and 69.1% of the variability that was associated with mean eccentric power output for 40% and 80% 1RM loads. Stretch velocity in combination with maximal strength was found to be the best two-predictor model of power absorption (R ²=83.7–97.3%). The best single predictor of SSC power production was found to be concentric mean power output (R ²=49.2–88.0%). The utilisation of the power absorbed during the power production phase differed across loads. It was suggested that as maximal strength is more trainable than speed, training to improve power absorption might emphasise maximal strength development. It was also suggested that SSC power output might benefit from training methods that focus on concentric force development. Further research is needed to evaluate these hypotheses and whether the findings of this study are similar for fast SSC motion. Electronic Publication     

Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner

FoxP3⁺ Treg cells and anergic T cells are the two regulatory phenotypes of T‐cell responses associated with helminth infection. Here, we examine the T‐cell responses in mice during Fasciola hepatica infection, and to its tegumental coat antigens (FhTeg) that are shed from the fluke every 2–3 h. FhTeg comprises a rich source of glycoproteins, mainly oligomannose N‐glycans that bind to mannose receptor. This study demonstrated a novel mechanism for the T‐cell unresponsiveness observed during F. hepatica infection and after injection with FhTeg. Markers of T‐cell anergy, such as GRAIL, EGR2, ICOS, and ITCH, are enhanced amongst CD4⁺ T‐cell populations during infection and following FhTeg injection. This is characterized by a lack of cytokine responses and reduced proliferative activity, which can be reversed with the addition of IL‐2. FhTeg‐activated dendritic cells (DCs) suppress T cells in vitro as measured by enhanced GRAIL and CTLA4 by RNA and suppressed cytokine expression in anti‐CD3 stimulated CD4⁺ T cells. FhTeg‐treated DCs have enhanced MR expression, which is critical for DC‐CD4⁺ T‐cell communication. Taken together, this study presents markers of anergy in a mouse model of F. hepatica infection, and improves our understanding of host–pathogen interactions and how helminths modulate host immunity.     

Inspiratory muscle strength training improves lung function in patients with the hypermobile Ehlers–Danlos syndrome: A randomized controlled trial

As exertional inspiratory dyspnea is a common disabling complaint in hypermobile Ehlers–Danlos syndrome (hEDS) often also known as joint hypermobility syndrome (JHS), we investigated inspiratory muscle (IM) strength in patients with hEDS, and we assessed the effects of IM training (IMT) on IM strength, lung function, and exercise capacity. A prospective evaluation of IM strength followed by a randomized controlled trial of IMT was performed in women with hEDS. Sniff nasal inspiratory pressure (SNIP) was used to routinely measure IM strength and IMT was carried out using a pressure threshold device. IM strength (main outcome), cardiopulmonary function, exercise capacity, and emotional distress of both the treated and control groups were evaluated at the start and at the end of the 6‐week training period. IM strength was reduced (<80% of predicted) in 77% of patients (80/104). Lung function was normal, although 24% of patients had a higher forced expiratory vital capacity (FVC) than normal and 12% of patients had a higher total lung capacity (TLC) than normal. Both the IMT and control groups (n = 20) had similar baseline characteristics. Significant changes were noted only in the IMT group after IMT. At the end of the program, IMT improved SNIP (20%) (before: 41 ± 17 cm H₂O [28, 53] vs. after: 49 ± 18 cm H₂O [34;65]), six‐minute walking distance (6MWD) (60 m) (455 ± 107 m [379,532] vs. 515 ± 127 m [408, 621]), and forced expiratory volume in one second (FEV1) (285 mL) (94 ± 14% pred [84,104] vs. 103 ± 11% pred [94, 112]). IM strength is significantly reduced in patients with hEDS. IMT improved IM strength, lung function, and exercise capacity. Our findings suggest that IMT should be added to usual care.     

Force–frequency relation in frog‐ventricle is dependent on the direction of sodium/calcium exchange in diastole

Aim: Force of contraction increases with stimulus‐frequency in mammalian and amphibian hearts under control conditions. Here, we have analysed the mechanism of the force–frequency relation (FFR) in frog‐ventricle. Methods: Circular strips of frog‐ventricle were subjected to field‐stimulation with frequencies in the range 0.03–0.2 Hz and force recorded on a chart‐recorder. In another protocol, varying rest‐periods were imposed while the preparation beat steadily at 0.2 Hz and the effect of rest on post‐rest beat amplitude was noted. Results: Under control conditions, a positive FFR and a rest‐induced decay of contraction amplitude (RID) were seen in the frequency range 0.03–0.2 Hz. With cadmium, nifedipine, nickel (40 μmol L^?1), ryanodine and adrenaline (all drugs at 10 μmol L^?1 concentration, except nickel), the positive FFR and RID seen under control conditions persisted. When the bathing solution contained ouabain (10 μmol L^?1) or low external sodium (40 mmol L^?1), or high external calcium (5 mmol L^?1), the FFR turned negative in the frequency range stated above and there were rest‐induced potentiations (RIP). Conclusion: When the conditions favour a net leak of calcium in diastole from intracellular stores via the calcium‐extrusive mode of sodium–calcium exchanger (NCX), FFR is positive. An increase in frequency lessens the diastolic interval and therefore the diastolic calcium leak, thereby augmenting force. On the other hand, interventions which favour the calcium‐acquisitive mode of NCX during diastole, changed the pattern of RID to RIP and converted FFR from positive to negative. With net diastolic calcium uptake, there is better store‐filling and therefore higher force at lower frequencies.