Atrial remodelling associated with sporting discipline, sex and duration in elite sports: a cross-sectional echocardiographic study among Danish elite athletes.

Background: Elite endurance training is characterised by a high-volume load of the heart and has been associated with atrial fibrillation (AF) in middle-aged men. We compared left atrial (LA) remodelling among elite athletes engaged in sports, categorised as having low, intermediate, and high cardiac demands. Methods: This cross-sectional echocardiographic study of healthy elite athletes evaluated LA size and function measured as LA maximum volume (maxLAVi) and contraction strain. Athletes were grouped according to the cardiac demands of their sport (low, intermediate, high). Morphological measures were indexed to body surface area and reported as least square means; differences between groups were reported with 95% CIs. Results: We included 482 elite athletes (age 21±5 years (mean±SD), 39% women). MaxLAVi was larger in the high group (28.4 mL/m2) compared with the low group (20.2 mL/m2; difference: 8.2, CI 5.3 to 11.1 mL/m2; p<0.001), where measurements in men exceed those in women (26.4 mL/m2 vs 24.7 mL/m2; difference 1.6 mL/m2; CI 0.3 to 2.9 mL/m2; p=0.0175). In the high group, LA contraction strain was lower compared with the low group (-10.1% vs -12.9%; difference: 2.8%; CI 1.3 to 4.3%; p<0.001), and men had less LA contraction strain compared with women (-10.3% vs -11.0%; difference 0.7%; CI 0.0 to 1.4%; p=0.049). Years in training did not affect maxLAVi or LA contraction strain. Conclusion: MaxLAVi was higher while LA contraction strain was lower with increased cardiac demands. MaxLAVi was larger, and LA contraction was lower in men compared with women. Whether these sex-based differences in LA remodelling are a precursor to pathological remodelling in male athletes is unknown.

Influence of type of sport on cardiac repolarization assessed by electrocardiographic T-wave morphology combination score.

INTRODUCTION: Interpreting repolarization changes in the electrocardiograms of athletes present a clinical challenge. AIM: Assessment of cardiac repolarization by T-wave morphology using the Morphology Combination Score (MCS), and evaluate how this quantitative description of T-wave morphology was influenced by the sport performed. MATERIALS AND METHODS: Digital electrocardiograms of 469 young elite athletes were analyzed for T-wave asymmetry, flatness and notching, and combined in the MCS. Athletes >22years were compared to a sex-and age matched control group from the general population (N=198). RESULTS: MCS increased with increasing endurance component of the sport performed ranging from 0.79±0.15 (low) to 0.92±0.21 (high) (p<0.0001). All subcomponents of MCS were increased compared to controls. MCS was unrelated to age, sex and ECG findings of the athlete's heart. CONCLUSION: This study suggests that sport induces repolarization changes detected by T-wave morphology, and a greater level of changes is seen in athletes from high endurance sports.

Eph receptors and ephrin class B ligands are expressed at tissue boundaries in Hydra vulgaris.

Eph receptors and ephrins are important players in axon guidance, cell sorting and boundary formation. Both the receptors and the ligands are integrated transmembrane proteins and signalling is bidirectional. The prevalent outcome of signal transduction is repulsion of adjacent cells or cell populations. Eph/ephrins have been identified in all multicellular animals from human to sponge, their functions however appear to have been altered during evolution. Here we have identified four Eph receptors and three class B ligands in the cnidarian Hydra vulgaris, indicating that those are the evolutionary older ones. In situ hybridisation experiments revealed a striking complementarity of expression of receptors and ligands in tentacles and in developing buds. This suggests that the original function of ephrin signalling may have been in epithelial cell adhesion and the formation of tissue boundaries.

Notch-signalling is required for head regeneration and tentacle patterning in Hydra.

Local self-activation and long ranging inhibition provide a mechanism for setting up organising regions as signalling centres for the development of structures in the surrounding tissue. The adult hydra hypostome functions as head organiser. After hydra head removal it is newly formed and complete heads can be regenerated. The molecular components of this organising region involve Wnt-signalling and ß-catenin. However, it is not known how correct patterning of hypostome and tentacles are achieved in the hydra head and whether other signals in addition to HyWnt3 are needed for re-establishing the new organiser after head removal. Here we show that Notch-signalling is required for re-establishing the organiser during regeneration and that this is due to its role in restricting tentacle activation. Blocking Notch-signalling leads to the formation of irregular head structures characterised by excess tentacle tissue and aberrant expression of genes that mark the tentacle boundaries. This indicates a role for Notch-signalling in defining the tentacle pattern in the hydra head. Moreover, lateral inhibition by HvNotch and its target HyHes are required for head regeneration and without this the formation of the ß-catenin/Wnt dependent head organiser is impaired. Work on prebilaterian model organisms has shown that the Wnt-pathway is important for setting up signalling centres for axial patterning in early multicellular animals. Our data suggest that the integration of Wnt-signalling with Notch-Delta activity was also involved in the evolution of defined body plans in animals.

The putative Notch ligand HyJagged is a transmembrane protein present in all cell types of adult Hydra and upregulated at the boundary between bud and parent.

BACKGROUND: The Notch signalling pathway is conserved in pre-bilaterian animals. In the Cnidarian Hydra it is involved in interstitial stem cell differentiation and in boundary formation during budding. Experimental evidence suggests that in Hydra Notch is activated by presenilin through proteolytic cleavage at the S3 site as in all animals. However, the endogenous ligand for HvNotch has not been described yet. RESULTS: We have cloned a cDNA from Hydra, which encodes a bona-fide Notch ligand with a conserved domain structure similar to that of Jagged-like Notch ligands from other animals. Hyjagged mRNA is undetectable in adult Hydra by in situ hybridisation but is strongly upregulated and easily visible at the border between bud and parent shortly before bud detachment. In contrast, HyJagged protein is found in all cell types of an adult hydra, where it localises to membranes and endosomes. Co-localisation experiments showed that it is present in the same cells as HvNotch, however not always in the same membrane structures. CONCLUSIONS: The putative Notch ligand HyJagged is conserved in Cnidarians. Together with HvNotch it may be involved in the formation of the parent-bud boundary in Hydra. Moreover, protein distribution of both, HvNotch receptor and HyJagged indicate a more widespread function for these two transmembrane proteins in the adult hydra, which may be regulated by additional factors, possibly involving endocytic pathways.