Dissociation of Increases in PGC-1α and Its Regulators from Exercise Intensity and Muscle Activation Following Acute Exercise

Muscle activation as well as changes in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) following high-intensity interval exercise (HIIE) were examined in young healthy men (n  = 8; age, 21.9±2.2 yrs; VO₂peak, 53.1±6.4 ml/min/kg; peak work rate, 317±23.5 watts). On each of 3 visits HIIE was performed on a cycle ergometer at a target intensity of 73, 100, or 133% of peak work rate. Muscle biopsies were taken at rest and three hours after each exercise condition. Total work was not different between conditions (∼730 kJ) while average power output (73%, 237±21; 100%, 323±26; 133%, 384±35 watts) and EMG derived muscle activation (73%, 1262±605; 100%, 2089±737; 133%, 3029±1206 total integrated EMG per interval) increased in an intensity dependent fashion. PGC-1α mRNA was elevated after all three conditions (p<0.05), with a greater increase observed following the 100% condition (∼9 fold, p<0.05) compared to both the 73 and 133% conditions (∼4 fold). When expressed relative to muscle activation, the increase in PGC-1α mRNA for the 133% condition was less than that for the 73 and 100% conditions (p<0.05). SIRT1 mRNA was also elevated after all three conditions (∼1.4 fold, p<0.05), with no difference between conditions. These findings suggest that intensity-dependent increases in PGC-1α mRNA following submaximal exercise are largely due to increases in muscle recruitment. As well, the blunted response of PGC-1α mRNA expression following supramaximal exercise may indicate that signalling mediated activation of PGC-1α may also be blunted. We also indentify that increases in PDK4, SIRT1, and RIP140 mRNA following acute exercise are dissociated from exercise intensity and muscle activation, while increases in EGR1 are augmented with supramaximal HIIE (p<0.05).     

Lactate consumption mediates repeated high-intensity interval exercise-enhanced executive function in adult males

[Purpose] Lactate is a principal energy substrate for the brain during exercise. A single bout of high-intensity interval exercise (HIIE) can increase the blood lactate level, brain lactate uptake, and executive function (EF). However, repeated HIIE can attenuate exercise-induced increases in lactate level and EF. The lactate levels in the brain and blood are reported to be correlated with exercise-enhanced EF. However, research is yet to explain the cause-and-effect relationship between lactate and EF. This study examined whether lactate consumption improves the attenuated exerciseenhanced EF caused by repeated HIIE.[Methods] Eleven healthy men performed two sets of HIIE, and after each set, 30 min were given for rest and examination. In the 2^nd set, the subjects consumed experimental beverages containing (n = 6) and not containing (n = 5) lactate. Blood, cardiovascular, and psychological variables were measured, and EF was evaluated by the computerized color–word Stroop test.[Results] The lactate group had a higher EF (P < 0.05) and tended to have a higher blood lactate level (P = 0.082) than the control group in the 2^nd set of HIIE. Moreover, blood lactate concentration was correlated with the interference score (i.e., reverse score of EF) (r = -0.394; P < 0.05).[Conclusion] Our results suggest that the attenuated exercise-enhanced EF after repeated HIIE can be improved through lactate consumption. However, the role of lactate needs to be elucidated in future studies, as it can be used for improving athletes’ performance and also in cognitive decline-related clinical studies.     

Release of Intracoronary Microparticles during Stent Implantation into Stable Atherosclerotic Lesions under Protection with an Aspiration Device

Objective

Stent implantation into atherosclerotic coronary vessels impacts on downstream microvascular function and induces the release of particulate debris and soluble substances, which differs qualitatively and quantitatively between native right coronary arteries (RCAs) and saphenous vein grafts on right coronary arteries (SVG-RCAs). We have now quantified the release of microparticles (MPs) during stent implantation into stable atherosclerotic lesions and compared the release between RCAs and SVG-RCAs.

Methods

In symptomatic, male patients with stable angina and a stenosis in their RCA or SVG-RCA, respectively (n = 14/14), plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation with a distal occlusion/aspiration device and divided into particulate debris and plasma. Particulate debris was weighed. Platelet-derived MPs (PMPs) were distinguished by flow cytometry as CD41⁺, endothelium-derived MPs (EMPs) as CD144⁺, CD62E⁺ and CD31⁺/CD41^-, leukocyte-derived MPs as CD45⁺, and erythrocyte-derived MPs as CD235⁺.

Results

In patients with comparable plaque volume and composition in RCAs and SVG-RCAs, intracoronary PMPs and EMPs were increased after stent implantation into their RCAs and SVG-RCAs (CD41⁺: 2729.6±645.6 vs. 4208.7±679.4 and 2355.9±503.9 vs. 3285.8±733.2 nr/µL; CD144⁺: 451.5±87.9 vs. 861.7±147.0 and 444.6±74.8 vs. 726.5±136.4 nr/µL; CD62E⁺: 1404.1±247.7 vs. 1844.3±378.6 and 1084.6±211.0 vs. 1783.8±384.3 nr/µL, P<0.05), but not different between RCAs and SVG-RCAs.

Conclusion

Stenting in stable atherosclerotic lesions is associated with a substantial release not only of PMPs, but also of EMPs in RCAs and SVG-RCAs. Their release does not differ between RCAs and SVG-RCAs.

Trial Registration

ClinicalTrials.gov NCT01430884     

Sprint interval training (SIT) is an effective method to maintain cardiorespiratory fitness (CRF) and glucose homeostasis in Scottish adolescents

The present study examined the physiological impact of a school based sprint interval training (SIT) intervention in replacement of standard physical education (SPE) class on cardio-respiratory fitness (CRF) and glucose homeostasis during the semester following summer vacation. Participants (n=49) were randomly allocated to either intervention (SIT; n=26, aged 16.9 ± 0.3 yrs) or control group who underwent standard physical education (SPE; n=23, aged 16.8 ± 0.6 yrs). CRF (VO₂max) and glucose homeostasis were obtained prior-to and following 7 weeks of SIT exercise. Significant group x time interaction was observed for CRF (P < 0.01) with non-significant trends for fasting insulin (P= 0.08), and HOMA-IR (P=0.06). CRF decreased (P < 0.01) in SPE such that POST intervention CRF was significantly lower (P< 0.05) in SPE. Fasting plasma glucose (P < 0.01), insulin (P< 0.01) and HOMA-IR (P< 0.01) increased significantly amongst SPE. The main finding of the present study is that 7-weeks of SIT exercise is an effective method of maintaining (but not improving) CRF and fasting insulin homeostasis amongst school-going adolescents. SIT exercise demonstrates potential as a time efficient physiological adjunct to standard PE class in order to maintain CRF during the school term.     

The anti-inflammatory effects of exercise training promote atherosclerotic plaque stabilization in apolipoprotein E knockout mice with diabetic atherosclerosis

Physical exercise is the cornerstone of cardiovascular disease treatment. The present study investigated whether exercise training affects atherosclerotic plaque composition through the modification of inflammatoryrelated pathways in apolipoprotein E knockout (apoE^−/−) mice with diabetic atherosclerosis. Forty-five male apoE^−/− mice were randomized into three equivalent (n=15) groups: control (CO), sedentary (SED), and exercise (EX). Diabetes was induced by streptozotocin administration. High-fat diet was administered to all groups for 12 weeks. Afterwards, CO mice were euthanatized, while the sedentary and exercise groups continued high-fat diet for 6 additional weeks. Exercising mice followed an exercise program on motorizedtreadmill (5 times/week, 60 min/session). Then, blood samples and atherosclerotic plaques in the aortic root were examined. A considerable (P<0.001) regression of the atherosclerotic lesions was observed in the exercise group (180.339±75.613×10³µm²) compared to the control (325.485±72.302×10³ µm²) and sedentary (340.188±159.108×10³µm²) groups. We found decreased macrophages, matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-8 and interleukin-6 (IL-6) concentrations (P<0.05) in the atherosclerotic plaques of the exercise group. Compared to both control and sedentary groups, exercise training significantly increased collagen (P<0.05), elastin (P<0.001), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) (P<0.001) content in the atherosclerotic plaques. Those effects paralleled with increased fibrous cap thickness and less internal elastic lamina ruptures after exercise training (P<0.05), while body-weight and lipid parameters did not significantly change. Plasma MMP-2 and MMP-3 concentrations in atherosclerotic tissues followed a similar trend. From our study we can conclude that exercise training reduces and stabilizes atherosclerotic lesions in apoE^−/− mice with diabetic atherosclerosis. A favorable modification of the inflammatory regulators seems to explain those beneficial effects.Key words: diabetes, atherosclerosis, exercise, matrix metalloproteinases, plaque stability.     

Short-Term Intensified Cycle Training Alters Acute and Chronic Responses of PGC1α and Cytochrome C Oxidase IV to Exercise in Human Skeletal Muscle

Reduced activation of exercise responsive signalling pathways have been reported in response to acute exercise after training; however little is known about the adaptive responses of the mitochondria. Accordingly, we investigated changes in mitochondrial gene expression and protein abundance in response to the same acute exercise before and after 10-d of intensive cycle training. Nine untrained, healthy participants (mean±SD; VO_2peak 44.1±17.6 ml/kg/min) performed a 60 min bout of cycling exercise at 164±18 W (72% of pre-training VO_2peak). Muscle biopsies were obtained from the vastus lateralis muscle at rest, immediately and 3 h after exercise. The participants then underwent 10-d of cycle training which included four high-intensity interval training sessions (6×5 min; 90–100% VO_2peak) and six prolonged moderate-intensity sessions (45–90 min; 75% VO_2peak). Participants repeated the pre-training exercise trial at the same absolute work load (64% of pre-training VO_2peak). Muscle PGC1-α mRNA expression was attenuated as it increased by 11- and 4- fold (P<0.001) after exercise pre- and post-training, respectively. PGC1-α protein expression increased 1.5 fold (P<0.05) in response to exercise pre-training with no further increases after the post-training exercise bout. RIP140 protein abundance was responsive to acute exercise only (P<0.01). COXIV mRNA (1.6 fold; P<0.01) and COXIV protein expression (1.5 fold; P<0.05) were increased by training but COXIV protein expression was decreased (20%; P<0.01) by acute exercise pre- and post-training. These findings demonstrate that short-term intensified training promotes increased mitochondrial gene expression and protein abundance. Furthermore, acute indicators of exercise-induced mitochondrial adaptation appear to be blunted in response to exercise at the same absolute intensity following short-term training.     

Inflammatory cytokines and metabolic responses to high-intensity intermittent training: effect of the exercise intensity

To examine the effects of two high-intensity intermittent training (HIIT) programs of varying intensities (100% vs. 110% of maximal aerobic velocity [MAV]) on metabolic, hormonal and inflammatory markers in young men. Thirty-seven active male volunteers were randomly assigned into: HIIT experimental groups (100% MAV [EG₁₀₀, n = 9] and 110% MAV [EG₁₁₀, n = 9]) and a control groups (CG₁₀₀, n = 9 and CG₁₁₀, n = 9). Particpants performed high intesity intermittent exercise test (HIIE) at 100% or 110% MAV. Venous blood samples were obtained before, at the end of HIIE and at 15 min of recovery, and before and after 8 weeks of HIIT programs. After training, Glucose was lower (p < 0.01) in EG₁₀₀ (d = 0.72) and EG₁₁₀ (d = 1.20) at the end of HIIE, and at 15 min recovery only in EG₁₁₀ (d = 0.95). After training, Insulin and Cortisol were lower than before training in EG₁₀₀ and EG₁₁₀ at the end of HIIE (p < 0.001). After HIIT, IL-6 deceased (p < 0.001) in EG₁₀₀ (d = 1.43) and EG₁₁₀ (d = 1.56) at rest, at the end of HIIE (d = 1.03; d = 1.75, respectively) and at 15 min of recovery (d = 0.88;d = 1.7, respectively). This decrease was more robust (p < 0.05) in EG₁₁₀ compared to EG₁₀₀. After HIIT, TNF-α deceased (p < 0.001) in EG₁₀₀ (d = 1.43) and EG₁₁₀ (d = 0.60) at rest, at the end of HIIE (0.71 < d < 0.98) and at 15 min of recovery (0.70 < d < 2.78). HIIT with 110% MAV is more effective in young males on the improvements of some metabolic (Glucose), hormonal (Cortisol) and inflammatory (IL-6) markers at rest, at the end of HIIE and 15 min of recovery than training at 100 % MAV.     

Exercise Intensity Modulates Glucose-Stimulated Insulin Secretion when Adjusted for Adipose,Liver and Skeletal Muscle Insulin Resistance

Little is known about the effects of exercise intensity on compensatory changes in glucose-stimulated insulin secretion (GSIS) when adjusted for adipose, liver and skeletal muscle insulin resistance (IR). Fifteen participants (8F, Age: 49.9±3.6yr; BMI: 31.0±1.5kg/m²; VO₂peak: 23.2±1.2mg/kg/min) with prediabetes (ADA criteria, 75g OGTT and/or HbA_1c) underwent a time-course matched Control, and isocaloric (200kcal) exercise at moderate (MIE; at lactate threshold (LT)), and high-intensity (HIE; 75% of difference between LT and VO₂peak). A 75g OGTT was conducted 1 hour post-exercise/Control, and plasma glucose, insulin, C-peptide and free fatty acids were determined for calculations of skeletal muscle (1/Oral Minimal Model; SM_IR), hepatic (HOMA_IR), and adipose (ADIPOSE_IR) IR. Insulin secretion rates were determined by deconvolution modeling for GSIS, and disposition index (DI; GSIS/IR; DI_SMIR, DI_HOMAIR, DI_ADIPOSEIR) calculations. Compared to Control, exercise lowered SM_IR independent of intensity (P<0.05), with HIE raising HOMA_IR and ADIPOSE_IR compared with Control (P<0.05). GSIS was not reduced following exercise, but DI_HOMAIR and DI_ADIPOSEIR were lowered more following HIE compared with Control (P<0.05). However, DI_SMIR increased in an intensity based manner relative to Control (P<0.05), which corresponded with lower post-prandial blood glucose levels. Taken together, pancreatic insulin secretion adjusts in an exercise intensity dependent manner to match the level of insulin resistance in skeletal muscle, liver and adipose tissue. Further work is warranted to understand the mechanism by which exercise influences the cross-talk between tissues that regulate blood glucose in people with prediabetes.     

Quadriceps and Respiratory Muscle Fatigue Following High-Intensity Cycling in COPD Patients

Exercise intolerance in COPD seems to combine abnormal ventilatory mechanics, impaired O₂ transport and skeletal muscle dysfunction. However their relatie contribution and their influence on symptoms reported by patients remain to be clarified. In order to clarify the complex interaction between ventilatory and neuromuscular exercise limiting factors and symptoms, we evaluated respiratory muscles and quadriceps contractile fatigue, dynamic hyperinflation and symptoms induced by exhaustive high-intensity cycling in COPD patients. Fifteen gold II-III COPD patients (age = 67±6 yr; BMI = 26.6±4.2 kg.m^-2) performed constant-load cycling test at 80% of their peak workload until exhaustion (9.3±2.4 min). Before exercise and at exhaustion, potentiated twitch quadriceps strength (Q_tw), transdiaphragmatic (P_di,tw) and gastric (P_ga,tw) pressures were evoked by femoral nerve, cervical and thoracic magnetic stimulation, respectively. Changes in operational lung volumes during exercise were assessed via repetitive inspiratory capacity (IC) measurements. Dyspnoea and leg discomfort were measured on visual analog scale. At exhaustion, Q_tw (-33±15%, >15% reduction observed in all patients but two) and P_di,tw (-20±15%, >15% reduction in 6 patients) were significantly reduced (P<0.05) but not P_ga,tw (-6±10%, >15% reduction in 3 patients). Percentage reduction in Q_tw correlated with the percentage reduction in P_di,tw (r=0.66; P<0.05). Percentage reductions in P_di,tw and P_ga,tw negatively correlated with the reduction in IC at exhaustion (r=-0.56 and r=-0.62, respectively; P<0.05). Neither dyspnea nor leg discomfort correlated with the amount of muscle fatigue. In conclusion, high-intensity exercise induces quadriceps, diaphragm and less frequently abdominal contractile fatigue in this group of COPD patients. In addition, the rise in end-expiratory lung volume and diaphragm flattening associated with dynamic hyperinflation in COPD might limit the development of abdominal and diaphragm muscle fatigue. This study underlines that both respiratory and quadriceps fatigue should be considered to understand the complex interplay of factors leading to exercise intolerance in COPD patients.     

The Positive Effects of Priming Exercise on Oxygen Uptake Kinetics and High-Intensity Exercise Performance Are Not Magnified by a Fast-Start Pacing Strategy in Trained Cyclists

The purpose of this study was to determine both the independent and additive effects of prior heavy-intensity exercise and pacing strategies on the VO2 kinetics and performance during high-intensity exercise. Fourteen endurance cyclists (VO₂max  = 62.8±8.5 mL.kg⁻¹.min⁻¹) volunteered to participate in the present study with the following protocols: 1) incremental test to determine lactate threshold and VO₂max; 2) four maximal constant-load tests to estimate critical power; 3) six bouts of exercise, using a fast-start (FS), even-start (ES) or slow-start (SS) pacing strategy, with and without a preceding heavy-intensity exercise session (i.e., 90% critical power). In all conditions, the subjects completed an all-out sprint during the final 60 s of the test as a measure of the performance. For the control condition, the mean response time was significantly shorter (p<0.001) for FS (27±4 s) than for ES (32±5 s) and SS (32±6 s). After the prior exercise, the mean response time was not significantly different among the paced conditions (FS = 24±5 s; ES = 25±5 s; SS = 26±5 s). The end-sprint performance (i.e., mean power output) was only improved (∼3.2%, p<0.01) by prior exercise. Thus, in trained endurance cyclists, an FS pacing strategy does not magnify the positive effects of priming exercise on the overall VO2 kinetics and short-term high-intensity performance.     

Circulating MicroRNA Responses between ‘High’ and ‘Low’ Responders to a 16-Wk Diet and Exercise Weight Loss Intervention

BackgroundInteractions between diet, physical activity and genetic predisposition contribute to variable body mass changes observed in response to weight loss interventions. Circulating microRNAs (c-miRNAs) may act as ‘biomarkers’ that are associated with the rate of change in weight loss, and/or play a role in regulating the biological variation, in response to energy restriction.ObjectiveTo quantify targeted c-miRNAs with putative roles in energy metabolism and exercise adaptations following a 16 wk diet and exercise intervention in individuals with large (high responders; HiRes) versus small (low responders; LoRes) losses in body mass.MethodsFrom 89 male and female overweight/obese participants who completed the intervention (energy restriction from diet, 250 kcal/d, and exercise, 250 kcal/d), subgroups of HiRes (>10% body mass loss, n = 22) and LoRes (<5% body mass loss, n = 18) were identified. From resting plasma samples collected after an overnight fast pre and post intervention, RNA was extracted, quantified and reverse transcribed. Thirteen c-miRNA selected a priori were analysed using a customised 96-well miScript miRNA PCR Array.ResultsLoss of body mass (-11.0 ± 2.3 kg vs. -3.0 ± 1.3 kg; P<0.01) and fat mass (-11.1 ± 2.6 kg vs. -3.9 ± 1.6 kg; P<0.01) was greater for HiRes than LoRes (P<0.001). Expression of c-miR-935 was higher in LoRes compared to HiRes pre- (~47%; P = 0.025) and post- (~100%; P<0.01) intervention and was the only c-miRNA differentially expressed at baseline between groups. The abundance of c-miR-221-3p and -223-3p increased pre- to post-intervention in both groups (~57–69% and ~25–90%, P<0.05). There was a post-intervention increase in c-miR-140 only in LoRes compared to HiRes (~23%, P = 0.016).ConclusionThe differential expression and responses of selected c-miRNAs in overweight/obese individuals to an exercise and diet intervention suggests a putative role for these ‘biomarkers’ in the prediction or detection of individual variability to weight loss interventions.     

Comparison of energy expenditure and substrate oxidation between walking and running in men and women

[Purpose]The present study compared energy metabolism between walking and running at equivalent speeds during two incremental exercise tests.[Methods]Thirty four university students (18 males, 16 females) were recruited. Each participant completed two trials, consisting of walking (Walk) and running (Run) trials on different days, with 2-3 days apart. Exercise on a treadmill was started from initial stage of 3 min (3.0 k/m in Walk trial, 5.0 km/h in Run trial), and the speed for walking and running was progressively every minute by 0.5 km/h. The changes in metabolic variables, heart rate (HR), and rating of perceived exertion (RPE) during exercise were compared between the trials.[Results]Energy expenditure (EE) increased with speed in each trial. However, the Walk trial had a significantly higher EE than the Run trial at speeds exceeding 92 ± 2 % of the maximal walking speed (MWS, p < 0.01). Similarly, carbohydrate (CHO) oxidation was significantly higher in the Walk trial than in the Run trial at above 92 ± 2 %MWS in males (p < 0.001) and above 93 ± 1 %MWS in females (p < 0.05).[Conclusion]These findings suggest that EE and CHO oxidation during walking increase non-linearly with speed, and walking at a fast speed causes greater metabolic responses than running at the equivalent speed in young participants.     

Twelve Weeks of Sprint Interval Training Improves Indices of Cardiometabolic Health Similar to Traditional Endurance Training despite a Five-Fold Lower Exercise Volume and Time Commitment

AimsWe investigated whether sprint interval training (SIT) was a time-efficient exercise strategy to improve insulin sensitivity and other indices of cardiometabolic health to the same extent as traditional moderate-intensity continuous training (MICT). SIT involved 1 minute of intense exercise within a 10-minute time commitment, whereas MICT involved 50 minutes of continuous exercise per session.MethodsSedentary men (27±8y; BMI = 26±6kg/m²) performed three weekly sessions of SIT (n = 9) or MICT (n = 10) for 12 weeks or served as non-training controls (n = 6). SIT involved 3x20-second ‘all-out’ cycle sprints (~500W) interspersed with 2 minutes of cycling at 50W, whereas MICT involved 45 minutes of continuous cycling at ~70% maximal heart rate (~110W). Both protocols involved a 2-minute warm-up and 3-minute cool-down at 50W.ResultsPeak oxygen uptake increased after training by 19% in both groups (SIT: 32±7 to 38±8; MICT: 34±6 to 40±8ml/kg/min; p<0.001 for both). Insulin sensitivity index (CS_I), determined by intravenous glucose tolerance tests performed before and 72 hours after training, increased similarly after SIT (4.9±2.5 to 7.5±4.7, p = 0.002) and MICT (5.0±3.3 to 6.7±5.0 x 10⁻⁴ min^-1 [μU/mL]^-1, p = 0.013) (p<0.05). Skeletal muscle mitochondrial content also increased similarly after SIT and MICT, as primarily reflected by the maximal activity of citrate synthase (CS; P<0.001). The corresponding changes in the control group were small for VO₂peak (p = 0.99), CS_I (p = 0.63) and CS (p = 0.97).ConclusionsTwelve weeks of brief intense interval exercise improved indices of cardiometabolic health to the same extent as traditional endurance training in sedentary men, despite a five-fold lower exercise volume and time commitment.     

Novel Cell-Free Strategy for Therapeutic Angiogenesis: In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation

Background

Current evidence suggests that endothelial progenitor cells (EPC) contribute to ischemic tissue repair by both secretion of paracrine factors and incorporation into developing vessels. We tested the hypothesis that cell-free administration of paracrine factors secreted by cultured EPC may achieve an angiogenic effect equivalent to cell therapy.

Methodology/Principal Findings

EPC-derived conditioned medium (EPC-CM) was obtained from culture expanded EPC subjected to 72 hours of hypoxia. In vitro, EPC-CM significantly inhibited apoptosis of mature endothelial cells and promoted angiogenesis in a rat aortic ring assay. The therapeutic potential of EPC-CM as compared to EPC transplantation was evaluated in a rat model of chronic hindlimb ischemia. Serial intramuscular injections of EPC-CM and EPC both significantly increased hindlimb blood flow assessed by laser Doppler (81.2±2.9% and 83.7±3.0% vs. 53.5±2.4% of normal, P<0.01) and improved muscle performance. A significantly increased capillary density (1.62±0.03 and 1.68±0.05/muscle fiber, P<0.05), enhanced vascular maturation (8.6±0.3 and 8.1±0.4/HPF, P<0.05) and muscle viability corroborated the findings of improved hindlimb perfusion and muscle function. Furthermore, EPC-CM transplantation stimulated the mobilization of bone marrow (BM)-derived EPC compared to control (678.7±44.1 vs. 340.0±29.1 CD34⁺/CD45⁻ cells/1×10⁵ mononuclear cells, P<0.05) and their recruitment to the ischemic muscles (5.9±0.7 vs. 2.6±0.4 CD34⁺ cells/HPF, P<0.001) 3 days after the last injection.

Conclusions/Significance

Intramuscular injection of EPC-CM is as effective as cell transplantation for promoting tissue revascularization and functional recovery. Owing to the technical and practical limitations of cell therapy, cell free conditioned media may represent a potent alternative for therapeutic angiogenesis in ischemic cardiovascular diseases.     

The Effect of High Intensity Interval Exercise on Postprandial Triacylglycerol and Leukocyte Activation – Monitored for 48h Post Exercise

Postprandial phenomenon are thought to contribute to atherogenesis alongside activation of the immune system. A single bout of high intensity interval exercise attenuates postprandial triacylglycerol (TG), although the longevity and mechanisms underlying this observation are unknown. The aims of this study were to determine whether this attenuation in postprandial TG remained 2 days after high intensity interval exercise, to monitor markers of leukocyte activation and investigate the underlying mechanisms. Eight young men each completed two three day trials. On day 1: subjects rested (Control) or performed 5 x 30 s maximal sprints (high intensity interval exercise). On day 2 and 3 subjects consumed high fat meals for breakfast and 3 h later for lunch. Blood samples were taken at various times and analysed for TG, glucose and TG-rich lipoprotein (TRL)-bound LPL-dependent TRL-TG hydrolysis (LTTH). Flow cytometry was used to evaluate granulocyte, monocyte and lymphocyte CD11b and CD36 expression. On day 2 after high intensity interval exercise TG area under the curve was lower (P<0.05) (7.46±1.53 mmol/l/7h) compared to the control trial (9.47±3.04 mmol/l/7h) with no differences during day 3 of the trial. LTTH activity was higher (P<0.05) after high intensity interval exercise, at 2 hours of day 2, compared to control. Granulocyte, monocyte and lymphocyte CD11b expression increased with time over day 2 and 3 of the study (P<0.0001). Lymphocyte and monocyte CD36 expression decreased with time over day 2 and 3 (P<0.05). There were no differences between trials in CD11b and CD36 expression on any leukocytes. A single session of high intensity interval exercise attenuated postprandial TG on day 2 of the study, with this effect abolished by day 3.The reduction in postprandial TG was associated with an increase in LTTH. High intensity interval exercise had no effect on postprandial responses of CD11b or CD36.     

Application of the Speed-Duration Relationship to Normalize the Intensity of High-Intensity Interval Training

The tolerable duration of continuous high-intensity exercise is determined by the hyperbolic Speed-tolerable duration (S-t_LIM) relationship. However, application of the S-t_LIM relationship to normalize the intensity of High-Intensity Interval Training (HIIT) has yet to be considered, with this the aim of present study. Subjects completed a ramp-incremental test, and series of 4 constant-speed tests to determine the S-t_LIM relationship. A sub-group of subjects (n = 8) then repeated 4 min bouts of exercise at the speeds predicted to induce intolerance at 4 min (WR₄), 6 min (WR₆) and 8 min (WR₈), interspersed with bouts of 4 min recovery, to the point of exercise intolerance (fixed WR HIIT) on different days, with the aim of establishing the work rate that could be sustained for 960 s (i.e. 4×4 min). A sub-group of subjects (n = 6) also completed 4 bouts of exercise interspersed with 4 min recovery, with each bout continued to the point of exercise intolerance (maximal HIIT) to determine the appropriate protocol for maximizing the amount of high-intensity work that can be completed during 4×4 min HIIT. For fixed WR HIIT t_LIM of HIIT sessions was 399±81 s for WR₄, 892±181 s for WR₆ and 1517±346 s for WR₈, with total exercise durations all significantly different from each other (P<0.050). For maximal HIIT, there was no difference in t_LIM of each of the 4 bouts (Bout 1: 229±27 s; Bout 2: 262±37 s; Bout 3: 235±49 s; Bout 4: 235±53 s; P>0.050). However, there was significantly less high-intensity work completed during bouts 2 (153.5±40. 9 m), 3 (136.9±38.9 m), and 4 (136.7±39.3 m), compared with bout 1 (264.9±58.7 m; P>0.050). These data establish that WR₆ provides the appropriate work rate to normalize the intensity of HIIT between subjects. Maximal HIIT provides a protocol which allows the relative contribution of the work rate profile to physiological adaptations to be considered during alternative intensity-matched HIIT protocols.     

Estimating excess post-exercise oxygen consumption using multiple linear regression in healthy Korean adults: a pilot study

[Purpose]This pilot study aimed to develop a regression model to estimate the excess post-exercise oxygen consumption (EPOC) of Korean adults using various easy-to-measure dependent variables.[Methods]The EPOC and dependent variables for its estimation (e.g., sex, age, height, weight, body mass index, fat-free mass [FFM], fat mass, % body fat, and heart rate_sum [HR_sum]) were measured in 75 healthy adults ( 31 males, 44 females). Statistical analysis was performed to develop an EPOC estimation regression model using the stepwise regression method.[Results]We confirmed that FFM and HR_sum were important variables in the EPOC regression models of various exercise types. The explanatory power and standard errors of estimates (SEE) for EPOC of each exercise type were as follows: the continuous exercise (CEx) regression model was 86.3% (R²) and 85.9% (adjusted R²), and the mean SEE was 11.73 kcal, interval exercise (IEx) regression model was 83.1% (R²) and 82.6% (adjusted R²), while the mean SEE was 13.68 kcal, and the accumulation of short-duration exercise (AEx) regression models was 91.3% (R²) and 91.0% (adjusted R²), while the mean SEE was 27.71 kcal. There was no significant difference between the measured EPOC using a metabolic gas analyzer and the predicted EPOC for each exercise type.[Conclusion]This pilot study developed a regression model to estimate EPOC in healthy Korean adults. The regression model was as follows: CEx = -37.128 + 1.003 × (FFM) + 0.016 × (HR_sum), IEx = -49.265 + 1.442 × (FFM) + 0.013 × (HR_sum), and AEx = -100.942 + 2.209 × (FFM) + 0.020 × (HR_sum).     

Alterations of Neuromuscular Function after the World's Most Challenging Mountain Ultra-Marathon

We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time  = 122.43 hours ±17.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean ± SD maximal voluntary contraction force declined significantly at Mid- (−13±17% and −10±16%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- (−24±13% and −26±19%, P<0.01) with alteration of the central activation ratio (−24±24% and −28±34% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: −18±18% and PF: −20±15%, P<0.01) and peak twitch (KE: −33±12%, P<0.001 and PF: −19±14%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719±3045 Ul·¹), lactate dehydrogenase (1145±511 UI·L⁻¹), C-Reactive Protein (13.1±7.5 mg·L⁻¹) and myoglobin (449.3±338.2 µg·L⁻¹) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half.     

Leukocytosis and Enhanced Susceptibility to Endotoxemia but Not Atherosclerosis in Adrenalectomized APOE Knockout Mice

Hyperlipidemic apolipoprotein E (APOE) knockout mice show an enhanced level of adrenal-derived anti-inflammatory glucocorticoids. Here we determined in APOE knockout mice the impact of total removal of adrenal function through adrenalectomy (ADX) on two inflammation-associated pathologies, endotoxemia and atherosclerosis. ADX mice exhibited 91% decreased corticosterone levels (P<0.001), leukocytosis (WBC count: 10.0 ± 0.4 x 10E9/L vs 6.5 ± 0.5 x 10E9/L; P<0.001) and an increased spleen weight (P<0.01). FACS analysis on blood leukocytes revealed increased B-lymphocyte numbers (55 ± 2% vs 46 ± 1%; P<0.01). T-cell populations in blood appeared to be more immature (CD62L+: 26 ± 2% vs 19 ± 1% for CD4+ T-cells, P<0.001 and 58 ± 7% vs 47 ± 4% for CD8+ T-cells, P<0.05), which coincided with immature CD4/CD8 double positive thymocyte enrichment. Exposure to lipopolysaccharide failed to increase corticosterone levels in ADX mice and was associated with a 3-fold higher (P<0.05) TNF-alpha response. In contrast, the development of initial fatty streak lesions and progression to advanced collagen-containing atherosclerotic lesions was unaffected. Plasma cholesterol levels were decreased by 35% (P<0.001) in ADX mice. This could be attributed to a decrease in pro-atherogenic very-low-density lipoproteins (VLDL) as a result of a diminished hepatic VLDL secretion rate (-24%; P<0.05). In conclusion, our studies show that adrenalectomy induces leukocytosis and enhances the susceptibility for endotoxemia in APOE knockout mice. The adrenalectomy-associated rise in white blood cells, however, does not alter atherosclerotic lesion development probably due to the parallel decrease in plasma levels of pro-atherogenic lipoproteins.