Quantification of patellar tendon strain and opportunities for personalized tendon loading during back squats.

Tendon strain during exercise is a critical regulatory factor in tendon adaptive responses and there are indications for an optimal range of strain that promotes tendon adaptation. Back squats are used to improve patellar tendon properties in sport and clinical settings. To date, the operating patellar tendon strain during back squats is unknown and current recommendations for individual exercise loading are based on the one repetition maximum (1RM). Here, we quantified patellar tendon strain during loaded back squats at 40, 60 and 80% of the 1RM and during maximum isometric knee extension contractions (MVC) using ultrasonography. Kinematics, ground reaction forces and muscle electromyographic activity were also recorded. Additionally, maximum tendon strain during the MVC and the percentage of 1RM were used as explanatory variables to estimate the individual patellar tendon strain during the squats. Strain increased with increasing 1RM loading (4.7 to 8.2%), indicating that already medium-loading back squats may provide a sufficient stimulus for tendon adaptation. The individual variability was, however, too high to generalize these findings. Yet, there was a high agreement between the individually estimated and measured patellar tendon strain (R2 = 0.858) during back squats. We argue that this approach may provide new opportunities for personalized tendon exercise.

Stability recovery performance in adults over a wide age range: A multicentre reliability analysis using different lean-and-release test protocols.

The ability to effectively increase the base of support is crucial to prevent from falling due to stability disturbances and has been commonly assessed using the forward-directed lean-and-release test. With this multicentre study we examined whether the assessment of stability recovery performance using two different forward lean-and-release test protocols is reliable in adults over a wide age range. Ninety-seven healthy adults (age from 21 to 80 years) were randomly assigned to one out of two lean angle protocols: gradual increase to maximal forward-lean angle (maximal lean angle; n = 43; seven participants were excluded due to marker artefacts) or predefined lean angle (single lean angle; n = 26; 21 participants needed to be excluded due to multiple stepping after release or marker artefacts). Both protocols were repeated after 0.5 h and 48 h to investigate intra- and inter-session reliability. Stability recovery performance was examined using the margin of stability at release (MoSRL) and touchdown (MoSTD) and increase in base of support (BoSTD). Intraclass correlation coefficients (confidence intervals at 95%) for the maximal lean angle and for the single lean angle were respectively 0.93 (0.89-0.96) and 0.94 (0.89-0.97) in MoSRL, 0.85 (0.77-0.91) and 0.67 (0.48-0.82) in MoSTD and 0.88 (0.81-0.93) and 0.80 (0.66-0.90) in BoSTD, with equivalence being revealed for each parameter between all three measurements (p < 0.01). We concluded that the assessment of stability recovery performance parameters in adults over a wide age range with the means of the forward lean-and-release test is reliable, independent of the used lean angle protocol.

Muscle and tendon adaptation in adolescent athletes: A longitudinal study.

There is evidence that a non-uniform adaptation of muscle and tendon in young athletes results in increased tendon stress during mid-adolescence. The present longitudinal study investigated the development of the morphological and mechanical properties of muscle and tendon of volleyball athletes in a time period of 2 years from mid-adolescence to late adolescence. Eighteen elite volleyball athletes participated in magnetic resonance imaging and ultrasound-dynamometry sessions to determine quadriceps femoris muscle strength, vastus lateralis, medialis and intermedius morphology, and patellar tendon mechanical and morphological properties in mid-adolescence (16 ± 1 years) and late adolescence (18 ± 1 years). Muscle strength, anatomical cross-sectional area (CSA), and volume showed significant (P < 0.05) but moderate increases of 13%, 6%, and 6%, respectively. The increase of patellar tendon CSA (P < 0.05) was substantially greater (27%) and went in line with increased stiffness (P < 0.05; 25%) and reduced stress (P < 0.05; 9%). During late adolescence, a pronounced hypertrophy of the patellar tendon led to a mechanical strengthening of the tendon in relation to the functional and morphological development of the muscle. These adaptive processes may compensate the unfavorable relation of muscle strength and tendon loading capacity in mid-adolescence and might have implications on athletic performance and tendon injury risk.

Asymmetry of Achilles tendon mechanical and morphological properties between both legs.

Although symmetry of Achilles tendon (AT) properties between legs is commonly assumed in research and clinical settings, different loading profiles of both legs in daily life (i.e., foot dominance) may affect the tendon properties in a side-depended manner. Therefore, AT properties were examined with regard to symmetry between legs. Thirty-six male healthy adults (28 ± 4 years), who were physically active but not involved in sports featuring dissimilar leg load participated. Mechanical and morphological AT properties of the non-dominant and dominant leg were measured by means of ultrasound, magnetic resonance imaging and dynamometry. The AT of the dominant leg featured a significant higher Young's modulus and length (P < 0.05) but a tendency toward lower maximum strain (P = 0.068) compared with the non-dominant leg. The tendon cross-sectional area and stiffness were not significantly different between sides. The absolute asymmetry index of the investigated parameters ranged from 3% to 31% indicating poor AT side symmetry. These findings provide evidence of distinct differences of AT properties between both legs in a population without any sport-specific side-depended leg loading. The observed asymmetry may be a result of different loading profiles of both legs during daily activities (i.e., foot dominance) and challenges the general assumption of symmetrical AT properties between legs.

Muscle shape consistency and muscle volume prediction of thigh muscles.

The present study investigated the applicability of a muscle volume prediction method using only the muscle length (L(M)), the maximum anatomical cross-sectional area (ACSA(max)), and a muscle-specific shape factor (p) on the quadriceps vastii. L(M), ACSA(max), muscle volume, and p were obtained from magnetic resonance images of the vastus intermedius (VI), lateralis (VL), and medialis (VM) of female (n = 20) and male (n = 17) volleyball athletes. The average p was used to predict muscle volumes (V(p)) using the equation V(p) = p × ACSA(max) × L(M). Although there were significant differences in the muscle dimensions between male and female athletes, p was similar and on average 0.582, 0.658, 0.543 for the VI, VL, and VM, respectively. The position of ACSA(max) showed low variability and was at 57%, 60%, and 81% of the thigh length for VI, VL, and VM. Further, there were no significant differences between measured and predicted muscle volumes with root mean square differences of 5-8%. These results suggest that the muscle shape of the quadriceps vastii is independent of muscle dimensions or sex and that the prediction method could be sensitive enough to detect changes in muscle volume related to degeneration, atrophy, or hypertrophy.

Evidence of imbalanced adaptation between muscle and tendon in adolescent athletes.

Adolescence may be regarded as a critical phase of tissue plasticity in young growing athletes, as the adaptation process of muscle-tendon unit is affected by both environmental mechanical stimuli and maturation. The present study investigated potential imbalances of knee extensor muscle strength and patellar tendon properties in adolescent compared with middle-aged athletes featuring long-term musculotendinous adaptations. Nineteen adolescent elite volleyball athletes [(A), 15.9 ± 0.6 years] and 18 middle-aged competitively active former elite volleyball athletes [(MA), 46.9 ± 0.6 years] participated in magnetic resonance imaging and ultrasound-dynamometry sessions to determine quadriceps femoris muscle strength, vastus lateralis morphology and patellar tendon mechanical and morphological properties. There was no significant age effect on the physiological cross-sectional area of the vastus lateralis and maximum knee extension moment (P > 0.05) during voluntary isometric contractions. However, the patellar tendon cross-sectional area was significantly smaller (A: 107.4 ± 27.5 mm(2) ; MA: 121.7 ± 39.8 mm(2) ) and the tendon stress during the maximal contractions was significantly higher in adolescent compared with the middle-aged athletes (A: 50.0 ± 10.1 MPa; MA: 40.0 ± 9.5 MPa). These findings provide evidence of an imbalanced development of muscle strength and tendon mechanical and morphological properties in adolescent athletes, which may have implications for the risk of tendon overuse injuries.

Effects of the Aspergillus fumigatus siderophore systems on the regulation of macrophage immune effector pathways and iron homeostasis.

The saprophytic fungus Aspergillus fumigatus is the most prevalent airborne fungal pathogen, which is responsible for invasive aspergillosis in immunocompromised patients. Iron plays an essential role for the growth and proliferation of A. fumigatus. This fungus synthesizes three major siderophores. It excretes triacetylfusarinine C to capture iron, while it accumulates ferricrocin and hydroxyferricrocin for hyphal and conidial iron storage, respectively. Herein, we investigated the role of the siderophore system of A. fumigatus in the modulation of immune effector pathways and iron homeostasis in macrophages. We set up a co-culture system consisting of the murine macrophage cell line RAW264.7 and either A. fumigatus wild type or a siderophore-deficient mutant (DeltasidA). We used real-time quantitative RT-PCR and Western blot analyses to study the expression of macrophage iron metabolism and innate immune response genes in response to pathogen challenge. Infection of macrophages with A. fumigatus wild type, but not with the DeltasidA mutant, induced expression of TNF and phagocyte oxidase subunit 47 at the transcriptional level. Moreover, infection with A. fumigatus wild type, but not with the DeltasidA mutant, compromised macrophage iron homeostasis. Infection with wild-type A. fumigatus decreased expression of the two cellular iron importers, the divalent metal transporter-1 and the transferrin receptor, and the only known iron exporter ferroportin. At the same time, it increased macrophage iron retention and ferritin synthesis. These data indicate that A. fumigatus affects the regulation of macrophage iron homeostasis and innate immune effector pathways via its siderophore system. The changes in immune response may be a consequence of macrophage iron restriction.

Relation between epicardial electrograms and signal-averaged electrocardiograms after acute myocardial infarction in dogs.

Signal-averaged electrocardiograms allow the non-invasive detection of late potentials which represent locally delayed conduction in the myocardium. To validate this method, it is necessary to compare the signal-averaged data with electrograms recorded directly from the heart. However, the studies performed to date involve only a consecutive collection of the invasively and non-invasively obtained data. To obtain a more direct comparison, we examined this relation at operation by simultaneous epicardial and signal-averaged measurements. Acute infarction in animals was chosen, because the ischemic area is a zone of delayed conduction whose presence can be verified in a signal-averaged electrocardiogram. For this purpose, the left anterior descending artery, proximal of large septal and diagonal branches, was tied off in nine mongrel dogs after thoracotomy. Before infarction, a signal-averaged electrocardiogram was recorded from the body surface. At the same time, epicardial electrograms were performed using bipolar electrodes both from the supply area of the left anterior descending artery and from that of the circumflex artery. Five minutes after coronary ligation, both the epicardial measurements and the signal-averaged electrocardiogram were repeated on the open thorax. Before occlusion of the left anterior descending artery, narrow activation complexes occurred in general in the epicardial electrograms and no late potentials were recorded in any dog by the signal-averaged electrocardiogram. Five minutes after coronary ligation, fractionated and prolonged electrograms occurred in the epicardial recordings from the ischemic zone, while the activation complexes in the uninfarcted supply area of the circumflex artery remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clenbuterol and fenoterol--animal experiment comparison of 2 tocolytic agents (with special reference to cardiovascular side effects)]. / Clenbuterol und Fenoterol--Tierexperimenteller Vergleich zweier Tokolytika (mit besonderer Berücksichtigung der kardiovaskulären Nebenwirkungen).

During animal experiments two substances, which are used for tocolysis (Fenoterol and Clenbuterol) have been compared regarding their tocolytic efficiency (determinations of myometrial cyclic AMP after long term treatment of the pregnant rat), their effects upon myocardial high energy phosphates (determinations of maternal myocardial high energy phosphates as well as of maternal and fetal myocardial cyclic AMP after long term treatment of the pregnant rat) and upon the hemodynamic situation (acute experiments with thoracotomized dogs). While significant hemodynamic derangements could be stated when using Fenoterol, no significant evidence for such alterations could be found during Clenbuterol administration during acute experiments. Determinations of myocardial high energy phosphates however reflected an augmented myocardial workload, both after Fenoterol and Clenbuterol administration. As by means of myometrial cyclic AMP determinations Clenbuterol proved to be at least as efficient as Fenoterol, concerning the tocolytic effect, Clenbuterol can be recommended as an oral tocolytic because of its pharmaco-cinetic advantages and the encouraging results from our hemodynamic investigations. According to results from chronical experiments an additional cardioprotection by means of magnesium substitution and eventually beta 1-blockade is still recommended.

[Antithrombin III substitution for optimization of the heparin effect during extracorporeal circulation in heart surgery]. / Antithrombin-III-Substitution zur Optimierung der Heparinwirkung während extrakorporaler Zirkulation in der Herzchirurgie.

In a prospective randomised study 20 patients undergoing coronary bypass surgery were assigned to two groups. Patients in group I (n = 10) received initially 250 IU heparin X kg-1 before the start of extracorporeal circulation. Patients in group II (n = 10) were given the same amount of heparin and in addition 1 000 units of purified human antithrombin III (AT III) concentrate. A highly significant lower heparin coefficient [2.69 +/- 0.57 IU X kg-1 X min-1, which is a parameter of heparin consumption (units of heparin X kg-1 given per minute during the time of heparinisation)], was found in group II compared to group I (3.73 +/- 0.56 IU X kg-1 min-1). Heparin sensitivity, measured as an increase in the ratio of activated coagulation time (ACT) X IU heparin-1 X kg-1 as a response to initial heparin dose, was found to be significantly higher (1.22 +/- 0.30 sec X IU heparin-1 X kg-1) in patients receiving AT III as measured in the control group (0.95 +/- 0.23 s X IU heparin-1 X kg-1). Mean values of ACT during the period of heparinisation were comparable (group I: 533 +/- 81 s, group II: 512 +/- 62 s) in the two groups. The substitution of AT III led to an increase of plasma AT III activity of 1.4% per substituted unit AT III X kg-1. AT III plasma activity, corrected to initial haematocrit levels to avoid dilution dependency, decreased as a consequence of extracorporeal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of the beta 1-blocker metoprolol on cyclic 3',5'-adenosine monophosphate in various tissues during long-term tocolysis with fenoterol. Animal experiments on the question of the interactive effects of the principal and adverse effects of beta 2-mimetics with special regard to fetal cardioprotection]. / Zum Einfluss des beta 1-Blockers Metoprolol auf das zyklische 3',5'-Adenosinmonophosphat in verschiedenen Gewebsarten unter Langzeittokolyse mit Fenoterol. Tierexperimentelle Untersuchungen zur Frage interaktiver Effekte bei Haupt- und Nebenwirkungen von beta 2-Mimetika unter besonderer Berücksichtigung der fetalen Kardioprotektion.

Using pregnant Wistar rats a comparative study was carried out, which was aimed to investigate the effect of long-term tocolysis (second half of gestation) with fenoterol alone as well as in combination with the cardioselective beta-blocker metoprolol (Beloc) upon the level of beta-adrenoceptor stimulation in maternal pulmonal, myocardial and myometrial tissue and in the myocardium of the fetuses. Radioimmunologic assessment of cyclic AMP tissue concentrations was used to obtain a parameter for beta-adrenoceptor stimulation. During treatment with fenoterol alone a significant rise of cyclic-AMP could be observed in all tissues, fetal myocardium showing the most pronounced rise. When combining fenoterol and metoprolol no derangement of the desired therapeutical beta 2-effect upon myometrium and lung could be found. Cyclic-AMP concentration in the maternal myocardium, however, was reduced significantly after combination therapy as compared to the monotherapy group, stressing the cardioprotective effect of metoprolol during beta 2-mimetic therapy, which yet has been demonstrated by means of other experimental models. As a similar tendency could be found in fetal myocardium, the conclusion may be drawn that combining metoprolol with fenoterol exerts also a fetal cardioprotection during beta 2-mimetic therapy of pregnant individuals. Furthermore possible effects of this combined therapy upon fetal beta-adrenergic reactions in general are discussed in this study.

[Magnesium aspartate as a cardioprotective agent and adjuvant in tocolysis with betamimetics. Animal experiments on the kinetics and calcium antagonist action of orally administered magnesium aspartate with special reference to simultaneous vitamin B administration]. / Magnesiumaspartat als Kardioprotektivum und Adjuvans bei Tokolyse mit Betamimetika. Tierexperimentelle Untersuchungen zu Kinetik und kalzium-antagonistischer Wirksamkeit oral applizierten Magnesiumaspartats unter besonderer Berücksichtigung von synchroner Vitamin B6-Gabe.

With pregnant Wistar-rats, suffering from alimentary magnesium deficiency, absorption and distributing of Mg28 has been studied, the latter having been applied as aspartate and as chloride, with and without simultaneous substitution of vitamin B6. Absorption and tissue pooling were found to be augmented when using the aspartate and even more when adding vitamin B6. These differences were significant in the blood as well as in fetal and myocardial tissue. Correlation between blood-Mg28 und Mg28-activities in various tissues shows, that blood magnesium levels indicate a magnesium deficiency at least in the tissues of interest: fetus, myocardium, uterus and placenta. Nevertheless blood magnesium levels fail to reflect an additional tissue pooling, that exerts a beneficial action in the respect of cardio protection and of saving beta-mimetic tocolytics. When measuring magnesium and calcium excretion during chronic experiments with and without oral magnesium aspartate substitution, it could be demonstrated, that the amount of substituted magnesium has been pooled almost totally. Oral magnesium substitution furthermore reduces intestinal calcium absorption. Investigation on calcium uptake into the maternal myocardium revealed, that oral magnesium aspartate substitution significantly diminishes myocardial calcium uptake, the latter among others being responsible for cardiac hazards during tocolysis with beta-mimetic substances, while the pharmacologic calcium-antagonist Verapamil failed to do so.

[The cardiac hazard of tocolysis and antagonizing possibilities. II. Communication: protection of the myocardium by means of substitution of magnesium]. / Das kardiale Risiko bei Tokolyse und Möglichkeiten zu dessen Antagonisierung. II. Mitteilung: Kardioprotektion durch Magnesiumsubstitution.

In a comparative study the value of the substitution of magnesium for the evaluation of cardiac side-effects of tocolysis has been assessed with regard to haemodynamic as well as to metabolic and morphologic alterations. Haemodynamic studies at the thoracotomized dog using the technique described in the first publication showed significantly less severe haemodynamic alterations in a group with normal magnesium blood levels than in the second group with reduced magnesium blood levels. Significant differences could be found at systolic blood pressure, cardiac output, velocity and acceleration of pressure rising, total peripherial resistance, myocardial contraction status and myocardial oxygen consumption. Likewise, a beneficial tendency could be found at the parameters: heart rate, Bretschneiders index of inotropy, pulmonal arterial pressure and coronary reserve. During chronic experiments at the rat, the addition of magnesiumaspartate led to a significantly improved preservation of high-energy phosphates in the myocardium with a concomitant reduction of lactic acid output. Also the increase of body weight was significantly higher when substituting magnesium. Microscopic examination showed no irritations of myocardial structure within the magnesium-substituted group, whereas lymphocytic infiltrations and a slight fibrosis of the endocardium could be seen at the animals having received only Fenoterol. Together, these findings lead to the conclusion, that the substitution of magnesium can act prophylactically against cardiac alterations, induced by Fenoterol. Consequently, magnesium deficiency, which frequently accompanies pregnancy, should be balanced before starting a tocolytic therapy.

[The cardiac hazard of tocolysis and antagonising possibilities. I. The haemodynamic situation of the patient during tocolysis/Protection of the myocardium by means of cardioselective beta-blockade. Experimental results (author's transl)]. / Das kardiale Risiko bei Tokolyse und Möglich-keiten zu dessen Antagonisierung. I. Mitteilung: Zur hämodynamischen Situation der tokolysierten Patientin/Kardioprotektion durch Kardioselektive beta-blocker. Tierexperimentelle Ergebnisse.

7 mongrel dogs underwent general anaesthesia and thoracotomy. For the assessment of the haemodynamic situation the following parameters were measured: Left ventricular and aortic pressure, coronary flow, oxygen-saturation in the coronary sinus, pulmonal arterial pressure, central venous pressure, heart rate. From these measurements cardiac output volume and myocardial oxygen consumption could be calculated. Using an ultrasound transit-time method regional myocardial function could be assessed. After the establishment of these measurements Fenoterol has been given in an increasing dosage up to the upper therapeutical range. Then additionally the cardioselective beta-antagonist Metoprolol was administered stepwise up to a total dose of 1.2 mg/kg body weight. The measurements proved evidence, that a relatively small dose of 0,2-0,4 mg Metoprolol/kg body weight is sufficient to compensate the haemodynamic situation impaired by Fenoterol, esp. the rise in myocardial oxygen consumption.

[Effect of the combination of the beta-1-blocker metoprolol with the tocolytic fenoterol on uteroplacental hemodynamics and fetal cardiovascular sensitivity with particular consideration of intrauterine fetal malnutrition. Results of animal experiments]. / Zur Auswirkung der Kombination des beta 1-Blockers Metoprolol mit dem Tokolytikum Fenoterol auf die uteroplazentare Hämodynamik und die fetale kardiovaskuläre Reagibilität unter besonderer Berücksichtigung der fetalen intrauterinen Mangelversorgung. Tierexperimentelle Ergebnisse.

7 merino sheep in an advanced state of pregnancy received oxytocin for labour induction under the conditions of control, monotherapy with the beta 2-adrenergic tocolytic fenoterol, combination of the latter with the beta 1-blocking substance metoprolol (Beloc). Likewise, the effect of labour induction was investigated when putting an artificial stenosis around the a. uterina during simultaneous application of fenoterol alone and combined with metoprolol. The following parameters were measured: aortic pressure and heart rate both in dam and fetus, maternal left ventricular pressure rising velocity, intrauterine pressure, uterine blood flow, uterine vascular resistance and regional myometrial contraction patterns by means of an ultrasonic transit time method. Measurement of maternal cardiovascular parameters once more showed, that maternal cardiovascular derangements could excellently be antagonised by metoprolol. Intrauterine pressure measurements as well as regional myometrial contraction patterns proved evidence, that there is no counteraction between the beta 2-mimetic substance and the beta 1-blocking agent concerning the tocolytic effect. When artificially stenosing the a. uterina, a rise in uterine contraction status could be observed; this hypoxic augmentation of myometrial tone could almost completely be reverted when combining fenoterol and metoprolol. Finally, no difference could be observed in the reaction of fetal cardiovascular parameters to reduced uterine blood flow before and after application of the beta 1-blocking substance metoprolol.