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Showing papers by "Ulrik Wisløff published in 2012"


Journal ArticleDOI
TL;DR: The results of the current study indicate that the risk of a cardiovascular event is low after both high- intensity exercise and moderate-intensity exercise in a cardiovascular rehabilitation setting, and such exercise should be considered among patients with coronary heart disease.
Abstract: Background Exercise performed at higher relative intensities has been found to elicit a greater increase in aerobic capacity and greater cardioprotective effects than exercise at moderate intensities. An inverse association has also been detected between the relative intensity of physical activity and the risk of developing coronary heart disease, independent of the total volume of physical activity. Despite that higher levels of physical activity are effective in reducing cardiovascular events, it is also advocated that vigorous exercise could acutely and transiently increase the risk of sudden cardiac death and myocardial infarction in susceptible persons. This issue may affect cardiac rehabilitation. Methods and results We examined the risk of cardiovascular events during organized high-intensity interval exercise training and moderate-intensity training among 4846 patients with coronary heart disease in 3 Norwegian cardiac rehabilitation centers. In a total of 175 820 exercise training hours during which all patients performed both types of training, we found 1 fatal cardiac arrest during moderate-intensity exercise (129 456 exercise hours) and 2 nonfatal cardiac arrests during high-intensity interval exercise (46 364 exercise hours). There were no myocardial infarctions in the data material. Because the number of high-intensity training hours was 36% of the number of moderate-intensity hours, the rates of complications to the number of patient-exercise hours were 1 per 129 456 hours of moderate-intensity exercise and 1 per 23 182 hours of high-intensity exercise. Conclusions The results of the current study indicate that the risk of a cardiovascular event is low after both high-intensity exercise and moderate-intensity exercise in a cardiovascular rehabilitation setting. Considering the significant cardiovascular adaptations associated with high-intensity exercise, such exercise should be considered among patients with coronary heart disease.

418 citations


Journal ArticleDOI
TL;DR: This study indicates that the blood pressure reducing effect of exercise in essential hypertension is intensity dependent, and aerobic interval training is an effective method to lower blood pressure and improve other cardiovascular risk factors.
Abstract: Aims: Exercise is recommended as prevention, management, and control of all stages of hypertension. There are still controversies about the optimal training dose, frequency, and intensity. We aimed...

307 citations


Journal ArticleDOI
TL;DR: The results suggest that increased CaMKII phosphorylation of RyR2 plays a role in the development of pathological sarcoplasmic reticulum Ca2+ leak and HF development in nonischemic forms of HF such as transverse aortic constriction in mice.
Abstract: Rationale: Increased activity of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is thought to promote heart failure (HF) progression. However, the importance of CaMKII phosphorylation of ryanodine receptors (RyR2) in HF development and associated diastolic sarcoplasmic reticulum Ca 2+ leak is unclear. Objective: Determine the role of CaMKII phosphorylation of RyR2 in patients and mice with nonischemic and ischemic forms of HF. Methods and Results: Phosphorylation of the primary CaMKII site S2814 on RyR2 was increased in patients with nonischemic, but not with ischemic, HF. Knock-in mice with an inactivated S2814 phosphorylation site were relatively protected from HF development after transverse aortic constriction compared with wild-type littermates. After transverse aortic constriction, S2814A mice did not exhibit pulmonary congestion and had reduced levels of atrial natriuretic factor. Cardiomyocytes from S2814A mice exhibited significantly lower sarcoplasmic reticulum Ca 2+ leak and improved sarcoplasmic reticulum Ca 2+ loading compared with wild-type mice after transverse aortic constriction. Interestingly, these protective effects on cardiac contractility were not observed in S2814A mice after experimental myocardial infarction. Conclusions: Our results suggest that increased CaMKII phosphorylation of RyR2 plays a role in the development of pathological sarcoplasmic reticulum Ca 2+ leak and HF development in nonischemic forms of HF such as transverse aortic constriction in mice.

197 citations


Journal ArticleDOI
TL;DR: AIT increased peak oxygen uptake more than the usual care rehabilitation provided to MI patients by Norwegian hospitals and reduced serum ferritin and resting heart rate and high-density lipoprotein cholesterol increased only after AIT.
Abstract: Objective: Exercise capacity strongly predicts survival and aerobic interval training (AIT) increases peak oxygen uptake effectively in cardiac patients. Usual care in Norway provides exercise training at the hospitals following myocardial infarction (MI), but the effect and actual intensity of these rehabilitation programmes are unknown.Design: Randomized controlled trial.Setting: Hospital cardiac rehabilitation.Subjects: One hundred and seven patients, recruited two to 12 weeks after MI, were randomized to usual care rehabilitation or treadmill AIT.Interventions: Usual care aerobic group exercise training or treadmill AIT as 4 × 4 minutes intervals at 85–95% of peak heart rate. Twice weekly exercise training for 12 weeks.Main measures: The primary outcome measure was peak oxygen uptake. Secondary outcome measures were endothelial function, blood markers of cardiovascular disease, quality of life, resting heart rate, and heart rate recovery.Results: Eighty-nine patients (74 men, 15 women, 57.4 ± 9.5 year...

176 citations


Journal ArticleDOI
03 Aug 2012-PLOS ONE
TL;DR: Evidence is provided that AET effectively counteracts redox imbalance and UPS overactivation, preventing skeletal myopathy and exercise intolerance in sympathetic hyperactivity-induced HF in mice and human HF, strengthening the clinical relevance of AET in the treatment of HF.
Abstract: © Cunha et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

135 citations


Journal ArticleDOI
TL;DR: Acute ingestion of dietary nitrate may not represent an effective strategy for reducing the oxygen cost of submaximal exercise or for enhancing endurance exercise performance in highly trained cross-country skiers.
Abstract: PurposeThe objective of this study is to examine the effects of acute ingestion of dietary nitrate on endurance running performance in highly trained cross-country skiers. Dietary nitrate has been shown to reduce the oxygen cost of submaximal exercise and improve tolerance of high-intensity

131 citations


Journal ArticleDOI
26 Dec 2012-PLOS ONE
TL;DR: The data suggest that VO2max is positively associated with telomere length, and it is found that long-term endurance exercise training may provide a protective effect on muscle telomeres length in older people.
Abstract: © 2012 Osthus et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

98 citations


Journal ArticleDOI
TL;DR: It is shown that two-way artificial selective breeding of rats for low and high intrinsic endurance exercise capacity also produces rats that differ for numerous disease risks, including the metabolic syndrome, cardiovascular complications, premature aging, and reduced longevity.

86 citations


Journal ArticleDOI
TL;DR: The aim of this study was to examine the effect of aerobic training versus strength training on circulating IL-18 and other proinflammatory markers in people with metabolic syndrome and found the latter intervention was associated with a more favorable inflammatory status.
Abstract: Background: Metabolic syndrome is associated with chronic low-grade inflammation, a condition thought to play a key role in the pathogenesis of the syndrome. Among a number of proinflammatory cytokines, interleukin-18 (IL-18) seems to be the best marker for inflammation among people with metabolic syndrome. The aim of this study was to examine the effect of aerobic training versus strength training on circulating IL-18 and other proinflammatory markers in people with metabolic syndrome. Methods: Thirty-one inactive men and women with metabolic syndrome were randomized to either high-intensity aerobic interval training (AIT, n=11), strength training (ST, n=10), or a control group (n=10). Exercise training was carried out three times per week for 12 weeks. Serum insulin, high-sensitivity C-reactive protein (hsCRP), IL-18, IL-6, and tumor necrosis factor-α (TNF-α) were measured before and after the intervention. Results: Serum IL-18 was reduced by 43% after AIT (P<0.001). Although there was no chang...

82 citations


Journal ArticleDOI
18 Jul 2012-PLOS ONE
TL;DR: Positive effects of home-based AIT in patients undergoing coronary artery bypass surgery are indicated, but more studies are needed to provide supporting evidence for the application of this rehabilitation strategy.
Abstract: © 2012 Moholdt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

73 citations


Journal ArticleDOI
TL;DR: High-intensity training of a restricted muscle group is highly effective in restoring skeletal muscle function in COPD patients and when normalised to citrate synthase activity, no difference in maximal respiration was found either after the intervention or compared to controls, suggesting normal functioning mitochondrial complexes.
Abstract: Improving reduced skeletal muscle function is important for optimising exercise tolerance and quality of life in chronic obstructive pulmonary disease (COPD) patients. By applying high-intensity training to a small muscle group, we hypothesised a normalisation of muscle function. Seven patients with COPD performed 6 weeks (3 days·week(-1)) of high-intensity interval aerobic knee extensor exercise training. Five age-matched healthy individuals served as a reference group. Muscle oxygen uptake and mitochondrial respiration of the vastus lateralis muscle were measured before and after the 6-week training programme. Initial peak work and maximal mitochondrial respiration were reduced in COPD patients and improved significantly after the training programme. Peak power and maximal mitochondrial respiration in vastus lateralis muscle increased to the level of the control subjects and were mainly mediated via improved complex I respiration. Furthermore, when normalised to citrate synthase activity, no difference in maximal respiration was found either after the intervention or compared to controls, suggesting normal functioning mitochondrial complexes. The present study shows that high-intensity training of a restricted muscle group is highly effective in restoring skeletal muscle function in COPD patients.

Journal ArticleDOI
TL;DR: AIT partly reversed the impaired age related diastolic function in healthy seniors at rest, improved LV diastsolic and systolic function during exercise as well as RV S′ at rest.
Abstract: Objectives. To study the effect of aerobic interval training (AIT) on myocardial function in sedentary seniors compared to master athletes (MA) and young controls. Design. Sixteen seniors (72± 1 years, 10 men) performed AIT (4 × 4 minutes) at ∼90% of maximal heart rate three times per week for 12 weeks. Results were compared with 11 male MA (74± 2 years) and 10 young males (23±2 years). Results. Seniors had an impaired diastolic function compared to the young at rest. AIT improved resting diastolic parameters, increased E/A ratio (44%, p <0.01), early diastolic tissue Doppler velocity (e′) (11%, p <0.05) and e′ during exercise (11%, p <0.01), shortened isovolumic relaxation rate (IVRT) (13%, p <0.01). Left ventricle (LV) systolic function (S′) was unaffected at rest, whereas S′ during stress echo increased by 29% (p <0.01). Right ventricle (RV) S′ and RV fractional area change (RFAC) increased (9%, p <0.01, 12%, p =0.01, respectively), but not RV e′. MA had the highest end-diastolic volume, stroke volume,...

Journal ArticleDOI
06 Dec 2012-PLOS ONE
TL;DR: No evidence is provided that endothelial function, an early indicator of atherosclerosis, is an important linking factor between insomnia and CHD, but individual insomnia symptoms may be related to endothelialfunction.
Abstract: Background: Insomnia is associated with increased risk of coronary heart disease (CHD), but the underlying mechanisms are not understood. To our knowledge, no previous studies have examined insomnia in relation to endothelial function, an indicator of preclinical atherosclerosis. Our aim was to assess the association of insomnia with endothelial function in a large population based study of healthy individuals. Methods: A total of 4 739 participants free from known cardiovascular or pulmonary diseases, cancer, and sarcoidosis, and who were not using antihypertensive medication were included in the study. They reported how often they had experienced difficulties falling asleep at night, repeated awakenings during the night, early awakenings without being able to go back to sleep, and daytime sleepiness. Endothelial function was measured by flow mediated dilation (FMD) derived from the brachial artery. Results: We found no consistent association between the insomnia symptoms and endothelial function in multiadjusted models, but individual insomnia symptoms may be related to endothelial function. Among women who reported early awakenings, endothelial function may be lower than in women without this symptom (p=0.03). Conclusions: This study provided no evidence that endothelial function, an early indicator of atherosclerosis, is an important linking factor between insomnia and CHD. Further studies are needed to explore the complex interrelation between sleep and cardiovascular pathology.

Journal ArticleDOI
TL;DR: The findings support current recommendations by showing that exercise of both "moderate intensity-long duration" and "vigorous intensity-short duration" was associated with similarly high VO(2peak), and suggest that exercising at very vigorous intensity may be beneficial for VO( 2peak) even with considerably lower total exercise time than expressed in today's recommendations.
Abstract: AB Purpose: The objective of this study is to examine how different approaches of the current exercise recommendations for adults associate with V[spacing dot above]O2peak in a large healthy population. We further examined how a lower duration than recommended, if performed at very vigorous intensity, was related to V[spacing dot above]O2peak. Methods: A total of 4631 healthy adults age 19-89 yr (2263 men and 2368 women) were tested for V[spacing dot above]O2peak (mean = 44.3 and 35.9 mL[middle dot]kg-1[middle dot]min-1 for men and women, respectively). Information on exercise habits was collected through a questionnaire, including questions on frequency, duration, and relative intensity (Borg scale 6-20). A general linear model was applied to assess the associations between physical activity and V[spacing dot above]O2peak. Results: V[spacing dot above]O2peak did not differ considerably between people who reported to exercise >=150 min[middle dot]wk-1 (average = 216 min[middle dot]wk-1, V[spacing dot above]O2peak = 45.2 and 36.5 mL[middle dot]kg-1[middle dot]min-1 for men and women, respectively) with moderate intensity and people who reported 75-149 min[middle dot]wk-1 (average = 112.5 min[middle dot]wk-1, V[spacing dot above]O2peak = 47.5 and 37.3 mL[middle dot]kg-1[middle dot]min-1 for men and women) with vigorous intensity, but it was higher than that in people who reported inactivity (V[spacing dot above]O2peak = 40.1 and 32.3 mL[middle dot]kg-1[middle dot]min-1 for men and women) or low-intensity exercise (V[spacing dot above]O2peak = 41.2 and 40.1 mL[middle dot]kg-1[middle dot]min-1 for men and women). Reporting exercise at very vigorous intensity but with a duration of less than 75 min[middle dot]wk-1 (average = 49 min[middle dot]wk-1) was associated with a V[spacing dot above]O2peak that was similarly high (47.6 and 36.7 mL[middle dot]kg-1[middle dot]min-1 for men and women). Conclusion: Our findings support current recommendations by showing that exercise of both "moderate intensity-long duration" and "vigorous intensity-short duration" was associated with similarly high V[spacing dot above]O2peak. Our results also suggest that exercising at very vigorous intensity may be beneficial for V[spacing dot above]O2peak even with considerably lower total exercise time than expressed in today's recommendations. (C)2012The American College of Sports Medicine

Journal ArticleDOI
18 Sep 2012-PLOS ONE
TL;DR: RHR is an important predictor of VO2peak, and serial assessments of RHR may provide useful and inexpensive information on cardiovascular fitness, and the results suggest that high levels of PA may compensate for the lower VO2 peak associated with a high RHR.
Abstract: © Nauman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Journal ArticleDOI
TL;DR: Diet as well as endurance exercise modulated the expression of perilipin mRNAs in human skeletal muscle, and perilipin 1 mRNA correlated positively with body fat mass, whereas none of the perilipins were associated with insulin sensitivity.
Abstract: The perilipin proteins enclose intracellular lipid droplets. We describe the mRNA expression of the five perilipins in human skeletal muscle in relation to fatty acid supply, exercise and energy balance. We observed that all perilipins were expressed in skeletal muscle biopsies with the highest mRNA levels of perilipin 2, 4 and 5. Cultured myotubes predominantly expressed perilipin 2 and 3. In vitro, incubation of myotubes with fatty acids enhanced mRNA expression of perilipin 1, 2 and 4. In vivo, low fat diet increased mRNA levels of perilipin 3 and 4. Endurance training, but not strength training, enhanced the expression of perilipin 2 and 3. Perilipin 1 mRNA correlated positively with body fat mass, whereas none of the perilipins were associated with insulin sensitivity. In conclusion, all perilipins mRNAs were expressed in human skeletal muscle. Diet as well as endurance exercise modulated the expression of perilipins.

Journal ArticleDOI
30 Jul 2012-PLOS ONE
TL;DR: Aerobic fitness dependent differences in serum levels of free choline and phosphatidylcholine are observed and should be further studied as potential early markers of CVD risk.
Abstract: © Bye et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Journal ArticleDOI
TL;DR: Exercise training improved the cardiomyocyte control of diastolic Ca2+ by reducing theCa2+ wave frequency and by improving the ability to abort spontaneous Ca2- waves after their generation, but before cell‐wide propagation.
Abstract: Impaired cardiac control of intracellular diastolic Ca2+ gives rise to arrhythmias. Whereas exercise training corrects abnormal cyclic Ca2+ handling in heart failure, the effect on diastolic Ca2+ remains unstudied. Here, we studied the effect of exercise training on the generation and propagation of spontaneous diastolic Ca2+ waves in failing cardiomyocytes. Post-myocardial infarction heart failure was induced in Sprague–Dawley rats by coronary artery ligation. Echocardiography confirmed left ventricular infarctions of 40 ± 5%, whereas heart failure was indicated by increased left ventricular end-diastolic pressures, decreased contraction-relaxation rates, and pathological hypertrophy. Spontaneous Ca2+ waves were imaged by laser linescanning confocal microscopy (488 nm excitation/505–530 nm emission) in 2 µM Fluo-3-loaded cardiomyocytes at 37°C and extracellular Ca2+ of 1.2 and 5.0 mM. These studies showed that spontaneous Ca2+ wave frequency was higher at 5.0 mM than 1.2 mM extracellular Ca2+ in all rats, but failing cardiomyocytes generated 50% (P < 0.01) more waves compared to sham-operated controls at Ca2+ 1.2 and 5.0 mM. Exercise training reduced the frequency of spontaneous waves at both 1.2 and 5.0 mM Ca2+ (P < 0.05), although complete normalization was not achieved. Exercise training also increased the aborted/completed ratio of waves at 1.2 mM Ca2+ (P < 0.01), but not 5.0 mM. Finally, we repeated these studies after inhibiting the nitric oxide synthase with L-NAME. No differential effects were found; thus, mediation did not involve the nitric oxide synthase. In conclusion, exercise training improved the cardiomyocyte control of diastolic Ca2+ by reducing the Ca2+ wave frequency and by improving the ability to abort spontaneous Ca2+ waves after their generation, but before cell-wide propagation. J. Cell. Physiol. 227: 20–26, 2012. © 2011 Wiley Periodicals, Inc.

Journal ArticleDOI
TL;DR: It is concluded that chronic CaMKII inhibition increased time to 50% re-lengthening which were recovered by exercise training, but paradoxically led to a greater increase in maximal oxygen uptake compared to sham mice.
Abstract: Activation of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role modulating cardiac function in both health and disease. Here, we determined the effect of chronic CaMKII inhibition during an exercise training program in healthy mice. CaMKII was inhibited by KN-93 injections. Mice were randomized to the following groups: sham sedentary, sham exercise, KN-93 sedentary, and KN-93 exercise. Cardiorespiratory function was evaluated by ergospirometry during treadmill running, echocardiography, and cardiomyocyte fractional shortening and calcium handling. The results revealed that KN-93 alone had no effect on exercise capacity or fractional shortening. In sham animals, exercise training increased maximal oxygen uptake by 8% (p < 0.05) compared to a 22% (p < 0.05) increase after exercise in KN-93 treated mice (group difference p < 0.01). In contrast, in vivo fractional shortening evaluated by echocardiography improved after exercise in sham animals only: from 25 to 32% (p < 0.02). In inactive mice, KN-93 reduced rates of diastolic cardiomyocyte re-lengthening (by 25%, p < 0.05) as well as Ca2+ transient decay (by 16%, p < 0.05), whereas no such effect was observed after exercise training. KN-93 blunted exercise training response on cardiomyocyte fractional shortening (63% sham vs. 18% KN-93; p < 0.01 and p < 0.05, respectively). These effects could not be solely explained by the Ca2+ transient amplitude, as KN-93 reduced it by 20% (p < 0.05) and response to exercise training was equal (64% sham and 47% KN-93; both p < 0.01). We concluded that chronic CaMKII inhibition increased time to 50% re-lengthening which were recovered by exercise training, but paradoxically led to a greater increase in maximal oxygen uptake compared to sham mice. Thus, the effect of chronic CaMKII inhibition is multifaceted and of a complex nature.

Journal ArticleDOI
TL;DR: In conclusion, soccer running performance does not appear to be the main cause of post soccer match-induced fatigue, and physical data provided by video match analysis systems is insufficient to accurately estimate the level of match fatigue.
Abstract: The purpose of this study was to analyse the impact of an intermittent test reproducing the soccer running activity profile on physical performance, subjective ratings and biochemical parameters throughout 72 h recovery. 8 professional soccer players performed the intermittent test on a non-motorised treadmill and data was collected before, immediately after, 24, 48 and 72 h after the test. Squat jump (SJ), countermovement jump (CMJ), peak isometric force (IFpeak), 6-s sprint, repeated sprints test (RS), perceptual ratings (fatigue, muscle soreness, stress), creatine kinase ([CK]) and uric acid ([UA]) were analyzed. After the test, a mean reduction in countermovement jump performance of -8.2% (CI: -12.9 to -3.4, p<0.01) was observed, while perceived fatigue (+2.1±1.7 a.u.; p<0.05), perceived muscle soreness (+1.8±1.5 a.u.; p<0.05), perceived stress (+1.6±1.5 a.u.; p<0.05), creatine kinase (+171±77 IU x l(-1); p<0.01) and uric acid (+168±89 Umol x l(-1); p<0.01) concentrations were significantly increased relative to baseline. No significant effect was found for SJ, IFpeak, 6-s sprint, RS immediately after and throughout the 72 h following the test. In conclusion, soccer running performance does not appear to be the main cause of post soccer match-induced fatigue. Physical data provided by video match analysis systems is insufficient to accurately estimate the level of match fatigue.

Journal ArticleDOI
TL;DR: The present review highlights the findings from the laboratory related to the hypothesis that VGE formation is the main mechanism behind serious decompression injuries, and introduces the thoughts for the future, and how the enigma of DCS should be approached.
Abstract: A key process in the pathophysiological steps leading to decompression sickness (DCS) is the formation of inert gas bubbles. The adverse effects of decompression are still not fully understood, but it seems reasonable to suggest that the formation of venous gas emboli (VGE) and their effects on the endothelium may be the central mechanism leading to central nervous system (CNS) damage. Hence, VGE might also have impact on the long-term health effects of diving. In the present review, we highlight the findings from our laboratory related to the hypothesis that VGE formation is the main mechanism behind serious decompression injuries. In recent studies, we have determined the impact of VGE on endothelial function in both laboratory animals and in humans. We observed that the damage to the endothelium due to VGE was dose dependent, and that the amount of VGE can be affected both by aerobic exercise and exogenous nitric oxide (NO) intervention prior to a dive. We observed that NO reduced VGE during decompression, and pharmacological blocking of NO production increased VGE formation following a dive. The importance of micro-nuclei for the formation of VGE and how it can be possible to manipulate the formation of VGE are discussed together with the effects of VGE on the organism. In the last part of the review we introduce our thoughts for the future, and how the enigma of DCS should be approached.



Journal ArticleDOI
TL;DR: An incorrect citation was included in the originalpublication:Vince RV, Chrismas B, Midgley AW, McNaughton LR, Madden LA (2009) Hypoxia mediated release of endo-thelial microparticles and increased association of S100A12 with circulating neutrophils.
Abstract: Erratum to: Eur J Appl PhysiolDOI 10.1007/s00421-011-1998-9An incorrect citation was included in the originalpublication:Vince RV, Chrismas B, Midgley AW, McNaughton LR,Madden LA (2009) Hypoxia mediated release of endo-thelial microparticles and increased association ofS100A12 with circulating neutrophils. Oxid Med CellLongev 2:2–6The correct reference should be:Vince RV, McNaughton LR, Taylor L, Midgley AW,Laden G, Madden LA (2009) Release of VCAM-1 asso-ciated endothelial microparticles following simulatedSCUBA dives. Eur J Appl Physiol 105:507–513