Daniela Flück

Six sessions of high-intensity interval training (HIT) are sufficient to improve exercise capacity. The mechanisms explaining such improvements are unclear. Accordingly, the aim of this study was to perform a comprehensive evaluation of physiologically relevant adaptations occurring after six sessions of HIT to determine the mechanisms explaining improvements in exercise performance. Sixteen untrained (43 ± 6 ml·kg(-1)·min(-1)) subjects completed six sessions of repeated (8-12) 60 s intervals of high-intensity cycling (100% peak power output elicited during incremental maximal exercise test) intermixed with 75 s of recovery cycling at a low intensity (30 W) over a 2-wk period. Potential training-induced alterations in skeletal muscle respiratory capacity, mitochondrial content, skeletal muscle oxygenation, cardiac capacity, blood volumes, and peripheral fatigue resistance were all assessed prior to and again following training. Maximal measures of oxygen uptake (Vo2peak; ∼8%; P = 0.026) and cycling time to complete a set amount of work (∼5%; P = 0.008) improved. Skeletal muscle respiratory capacities increased, most likely as a result of an expansion of skeletal muscle mitochondria (∼20%, P = 0.026), as assessed by cytochrome c oxidase activity. Skeletal muscle deoxygenation also increased while maximal cardiac output, total hemoglobin, plasma volume, total blood volume, and relative measures of peripheral fatigue resistance were all unaltered with training. These results suggest that increases in mitochondrial content following six HIT sessions may facilitate improvements in respiratory capacity and oxygen extraction, and ultimately are responsible for the improvements in maximal whole body exercise capacity and endurance performance in previously untrained individuals.

Key points This study assessed the respective contributions of haematological and skeletal muscle adaptations to any observed improvement in peak oxygen uptake ( ) induced by endurance training (ET). , peak cardiac output ( ), blood volumes and skeletal muscle biopsies were assessed prior (pre) to and after (post) 6 weeks of ET. Following the post‐ET assessment, red blood cell volume (RBCV) reverted to the pre‐ET level following phlebotomy and and were determined again. We speculated that the contribution of skeletal muscle adaptations to an ET‐induced increase in could be identified when offsetting the ET‐induced increase in RBCV. , , blood volumes, skeletal muscle mitochondrial volume density and capillarization were increased after ET. Following RBCV normalization, and reverted to pre‐ET levels. These results demonstrate the predominant contribution of haematological adaptations to any increase in induced by ET. Abstract It remains unclear whether improvements in peak oxygen uptake ( ) following endurance training (ET) are primarily determined by central and/or peripheral adaptations. Herein, we tested the hypothesis that the improvement in following 6 weeks of ET is mainly determined by haematological rather than skeletal muscle adaptations. Sixteen untrained healthy male volunteers (age = 25 ± 4 years, = 3.5 ± 0.5 l min −1 ) underwent supervised ET (6 weeks, 3–4 sessions per week). , peak cardiac output ( ), haemoglobin mass (Hb mass ) and blood volumes were assessed prior to and following ET. Skeletal muscle biopsies were analysed for mitochondrial volume density (Mito VD ), capillarity, fibre types and respiratory capacity (OXPHOS). After the post‐ET assessment, red blood cell volume (RBCV) was re‐established at the pre‐ET level by phlebotomy and and were measured again. We speculated that the contribution of skeletal muscle adaptations to the ET‐induced increase in would be revealed when controlling for haematological adaptations. and were increased ( P < 0.05) following ET (9 ± 8 and 7 ± 6%, respectively) and decreased ( P < 0.05) after phlebotomy (−7 ± 7 and −10 ± 7%). RBCV, plasma volume and Hb mass all increased ( P < 0.05) after ET (8 ± 4, 4 ± 6 and 6 ± 5%). As for skeletal muscle adaptations, capillary‐to‐fibre ratio and total Mito VD increased ( P < 0.05) following ET (18 ± 16 and 43 ± 30%), but OXPHOS remained unaltered. Through stepwise multiple regression analysis, , RBCV and Hb mass were found to be independent predictors of . In conclusion, the improvement in following 6 weeks of ET is primarily attributed to increases in and oxygen‐carrying capacity of blood in untrained healthy young subjects.

Abstract Aims (i) To determine whether exercise‐induced increases in muscle mitochondrial volume density (Mito VD ) are related to enlargement of existing mitochondria or de novo biogenesis and (ii) to establish whether measures of mitochondrial‐specific enzymatic activities are valid biomarkers for exercise‐induced increases in Mito VD . Method Skeletal muscle samples were collected from 21 healthy males prior to and following 6 weeks of endurance training. Transmission electron microscopy was used for the estimation of mitochondrial densities and profiles. Biochemical assays, western blotting and high‐resolution respirometry were applied to detect changes in specific mitochondrial functions. Result Mito VD increased with 55 ± 9% ( P < 0.001), whereas the number of mitochondrial profiles per area of skeletal muscle remained unchanged following training. Citrate synthase activity ( CS ) increased (44 ± 12%, P < 0.001); however, there were no functional changes in oxidative phosphorylation capacity ( OXPHOS , CI + II P ) or cytochrome c oxidase ( COX ) activity. Correlations were found between Mito VD and CS ( P = 0.01; r = 0.58), OXPHOS , CI + CIIP ( P = 0.01; R = 0.58) and COX ( P = 0.02; R = 0.52) before training; after training, a correlation was found between Mito VD and CS activity only ( P = 0.04; R = 0.49). Intrinsic respiratory capacities decreased ( P < 0.05) with training when respiration was normalized to Mito VD. This was not the case when normalized to CS activity although the percentage change was comparable . Conclusions Mito VD was increased by inducing mitochondrial enlargement rather than de novo biogenesis. CS activity may be appropriate to track training‐induced changes in Mito VD.

OBJECTIVES: We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity. METHODS: In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand). RESULTS: Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = -0.66, p = 0.003) and more microbleeds (r = -0.78, p < 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08). CONCLUSIONS: Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.

The aim was to determine the mechanisms facilitating exercise performance in hot conditions following heat training. In a counter-balanced order, seven males (V̇o2max 61.2 ± 4.4 ml·min(-1)·kg(-1)) were assigned to either 10 days of 90-min exercise training in 18 or 38°C ambient temperature (30% relative humidity) applying a cross-over design. Participants were tested for V̇o2max and 30-min time trial performance in 18 (T18) and 38°C (T38) before and after training. Blood volume parameters, sweat output, cardiac output (Q̇), cerebral perfusion (i.e., middle cerebral artery velocity [MCAvmean]), and other variables were determined. Before one set of exercise tests in T38, blood volume was acutely expanded by 538 ± 16 ml with an albumin solution (T38A) to determine the role of acclimatization induced hypervolemia on exercise performance. We furthermore hypothesized that heat training would restore MCAvmean and thereby limit centrally mediated fatigue. V̇o2max and time trial performance were equally reduced in T38 and T38A (7.2 ± 1.6 and 9.3 ± 2.5% for V̇o2max; 12.8 ± 2.8 and 12.9 ± 2.8% for time trial). Following heat training both were increased in T38 (9.6 ± 2.1 and 10.4 ± 3.1%, respectively), whereas both V̇o2max and time trial performance remained unchanged in T18. As expected, heat training augmented plasma volume (6 ± 2%) and mean sweat output (26 ± 6%), whereas sweat [Na(+)] became reduced by 19 ± 7%. In T38 Q̇max remained unchanged before (21.3 ± 0.6 l/min) to after (21.7 ± 0.5 l/min) training, whereas MCAvmean was increased by 13 ± 10%. However, none of the observed adaptations correlated with the concomitant observed changes in exercise performance.