Øyvind Ellingsen

Superior Cardiovascular Effect of Aerobic Interval Training Versus Moderate Continuous Training in Heart Failure Patients A Randomized Study

Background— Exercise training reduces the symptoms of chronic heart failure. Which exercise intensity yields maximal beneficial adaptations is controversial. Furthermore, the incidence of chronic heart failure increases with advanced age; it has been reported that 88% and 49% of patients with a first diagnosis of chronic heart failure are >65 and >80 years old, respectively. Despite this, most previous studies have excluded patients with an age >70 years. Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfarction heart failure. Methods and Results— Twenty-seven patients with stable postinfarction heart failure who were undergoing optimal medical treatment, including &bgr;-blockers and angiotensin-converting enzyme inhibitors (aged 75.5±11.1 years; left ventricular [LV] ejection fraction 29%; &OV0312;o2peak 13 mL · kg−1 · min−1) were randomized to either moderate continuous training (70% of highest measured heart rate, ie, peak heart rate) or aerobic interval training (95% of peak heart rate) 3 times per week for 12 weeks or to a control group that received standard advice regarding physical activity. &OV0312;o2peak increased more with aerobic interval training than moderate continuous training (46% versus 14%, P<0.001) and was associated with reverse LV remodeling. LV end-diastolic and end-systolic volumes declined with aerobic interval training only, by 18% and 25%, respectively; LV ejection fraction increased 35%, and pro-brain natriuretic peptide decreased 40%. Improvement in brachial artery flow-mediated dilation (endothelial function) was greater with aerobic interval training, and mitochondrial function in lateral vastus muscle increased with aerobic interval training only. The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups. No changes occurred in the control group. Conclusions— Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity, endothelial function, and quality of life in patients with postinfarction heart failure. These findings may have important implications for exercise training in rehabilitation programs and future studies.

Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats

OBJECTIVE Regular exercise enhances cardiac function and modulates myocyte growth in healthy individuals. The purpose of the present study was to assess contractile function and expression of selected genes associated with intracellular Ca2+ regulation after intensity controlled aerobic endurance training in the rat. METHODS Female Sprague-Dawley rats were randomly assigned to sedentary control (SED) or treadmill running (TR) 2 h per day, 5 days per week for 2, 4 or 13 weeks. Rats ran 8-min intervals at 85-90% of VO2max separated by 2 min at 50-60%. Myocyte length, intracellular Ca2+ (Fura-2), and intracellular pH (BCECF) were measured in dissociated cells in response to electrical stimulation at a range of stimulation rates. RESULTS The increase in VO2max plateaued after 6-8 weeks, 60% above SED. After 13 weeks, left and right ventricular weights were 39 and 36% higher than in SED. Left ventricular myocytes were 13% longer, whereas width remained unchanged. After 4 weeks training, myocyte contractility was approximately 20% higher in TR. Peak systolic intracellular Ca2+ and time for the decay from systole were 20-35 and 12-17% lower, respectively. These results suggest that increased myofilament Ca2+ sensitivity is the dominant effect responsible for enhanced myocyte contractility in TR. Intracellular pH progressively decreased as stimulation frequency was increased in the SED group. This decrease was markedly attenuated in TR and the intracellular pH was significantly higher in the TR group at a stimulation rate of 5-10 Hz. This effect may contribute to the increased contractility observed at the higher stimulation frequencies in TR. A higher intrinsic myofilament Ca2+ sensitivity was observed in permeabilised myocytes from the TR group under conditions of constant pH and [Ca2+]. Western blot analysis indicated 21 and 46% higher myocardial SERCA-2 and phospholamban, but unaltered Na+/Ca(2+)-exchanger levels. Competitive RT-PCR revealed that TR significantly increased Na+/H(+)-exchanger mRNA. CONCLUSION Intensity controlled interval training increases cardiomyocyte contractility. Higher myofilament Ca(2+)-sensitivity, and enhanced Ca(2+)-handling and pH-regulation are putative mechanisms. Our results suggest that physical exercise induces adaptive hypertrophy in cardiac myocytes with improved contractile function.

High-Intensity Interval Training to Maximize Cardiac Benefits of Exercise Training?

We hypothesized that high-intensity aerobic interval training results in a greater beneficial adaptation of the heart compared with that observed after low-to-moderate exercise intensity. This is supported by recent epidemiological, experimental, and clinical studies. Cellular and molecular mechanisms of myocardial adaptation to exercise training are discussed in this review.

Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility, Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction

OBJECTIVE Although it is generally accepted that endurance training improves cardiac function after myocardial infarction the sub-cellular mechanisms are uncertain. The present study reports the effects of aerobic endurance training on myocardial mass, myocyte dimensions, contractile function, Ca2+ handling, and myofilament responsiveness to Ca2+ in cardiomyocytes from healthy and failing rat hearts. METHODS Adult female Sprague-Dawley rats ran on a treadmill 1.5 h/day, 5 days a week for 8 weeks. Exercise intervals alternated between 8 min at 85-90% of V(O(2max)) and 2 min at 50-60%. Training started 4 weeks after ligation of the left coronary artery (TR-INF, n=11) or sham operation (TR-SHAM, n=6). Sedentary animals (SED-SHAM, n=6; SED-INF, n=13) were controls. RESULTS After 6 weeks V(O(2max)) in TR-INF and TR-SHAM leveled off 65% above sedentary controls. In TR-SHAM, left and right ventricle weights were approximately 25% higher than in SED-SHAM, myocytes were approximately 13% longer; width remained unchanged. At physiological stimulation frequencies, relative myocyte shortening was markedly higher whereas peak systolic [Ca2+] and t(1/2) of Ca2+ transient decay were 10-20% lower, indicating higher Ca2+ sensitivity in cardiomyocytes from trained rats, compared to respective controls. In TR-INF the left and right ventricular weights, and myocyte length and width were 15, 23, 12, and 20% less than in SED-INF. Endurance training significantly increased the myocardial SR Ca2+ pump (SERCA-2) and sarcolemmal Na+-Ca2+-exchanger (NCX) protein levels to the extent that TR-INF did not differ from SED-SHAM. CONCLUSION This is the first study to show that aerobic endurance training attenuates the ventricular and cellular hypertrophy in failing hearts. Furthermore, training consistently restores contractile function, intracellular Ca2+ handling, and Ca2+-sensitivity in cardiomyocytes from rats with myocardial infarction.

Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy

Cardiomyocyte hypertrophy differs according to the stress exerted on the myocardium. While pressure overload‐induced cardiomyocyte hypertrophy is associated with depressed contractile function, physiological hypertrophy after exercise training associates with preserved or increased inotropy. We determined the activation state of myocardial Akt signaling with downstream substrates and fetal gene reactivation in exercise‐induced physiological and pressure overload‐induced pathological hypertrophies. C57BL/6J mice were either treadmill trained for 6 weeks, 5 days/week, at 85–90% of maximal oxygen uptake (VO2max), or underwent transverse aortic constriction (TAC) for 1 or 8 weeks. Total and phosphorylated protein levels were determined with SDS‐PAGE, and fetal genes by real‐time RT‐PCR. In the physiologically hypertrophied heart after exercise training, total Akt protein level was unchanged, but Akt was chronically hyperphosphorylated at serine 473. This was accompanied by activation of the mammalian target of rapamycin (mTOR), measured as phosphorylation of its two substrates: the ribosomal protein S6 kinase‐1 (S6K1) and the eukaryotic translation initiation factor‐4E binding protein‐1 (4E‐BP1). Exercise training did not reactivate the fetal gene program (β‐myosin heavy chain, atrial natriuretic factor, skeletal muscle actin). In contrast, pressure overload after TAC reactivated fetal genes already after 1 week, and partially inactivated the Akt/mTOR pathway and downstream substrates after 8 weeks. In conclusion, changes in opposite directions of the myocardial Akt/mTOR signal pathway appears to distinguish between physiological and pathological hypertrophies; exercise training associating with activation and pressure overload associating with inactivation of the Akt/mTOR pathway. J. Cell. Physiol. 214: 316–321, 2008.

Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR (Part II)

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose–response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

Peak Oxygen Uptake and Cardiovascular Risk Factors in 4631 Healthy Women and Men

INTRODUCTION Many studies suggest that cardiorespiratory fitness, measured as peak oxygen uptake (VO2peak), may be the single best predictor of cardiovascular morbidity and premature cardiovascular mortality. However, current reference values are either estimates of oxygen uptake or come from small studies, mainly of men. Therefore, the aims of this study were to directly measure VO2peak in healthy adult men and women and to assess the association with cardiovascular risk factor levels. METHODS A cross-sectional study of 4631 volunteering, free-living Norwegian men (n = 2368) and women (n = 2263) age 20-90 yr. The data collection was from June 2007 to June 2008. Participants were free from known pulmonary or cardiovascular disease. VO2peak was measured by ergospirometry during treadmill running. Associations (odds ratios, OR) with unfavorable levels of cardiovascular risk factors and a cluster of cardiovascular risk factors were assessed by logistic regression analysis. RESULTS Overall, mean VO2peak was 40.0 ± 9.5 mL·kg(-1)·min(-1). Women below the median VO2peak (<35.1 mL·kg(-1)·min(-1)) were five times (OR = 5.4, 95% confidence interval = 2.3-12.9) and men below the median (<44.2 mL·kg(-1)·min(-1)) were eight times (OR = 7.9, 95% confidence interval = 3.5-18.0) more likely to have a cluster of cardiovascular risk factors compared to those in the highest quartile of VO2peak (≥40.8 and ≥50.5 mL·kg(-1)·min(-1) in women and men, respectively). Each 5-mL·kg(-1)·min(-1) lower VO2peak corresponded to ∼56% higher odds of cardiovascular risk factor clustering. CONCLUSIONS These data represent the largest reference material of objectively measured VO2peak in healthy men and women age 20-90 yr. Even in people considered to be fit, VO2peak was clearly associated with levels of conventional cardiovascular risk factors.

Time-course of endothelial adaptation following acute and regular exercise

Background Regular exercise training has emerged as a powerful tool to improve endothelium-dependent vasorelaxation. However, little is known about the magnitude of change and the permanence of exercise-induced adaptations in endothelial function. Design Rats were randomized to either 6 weeks of regular exercise or one bout of exercise. Rats were then sacrificed 0, 6, 12, 24, 48, 96 or 192h post-exercise, and vascular responsiveness to acetylcholine was determined. Methods Endothelium-dependent dilation was assessed by exposure to accumulating doses of acetylcholine in ring segments of the abdominal aorta from female Sprague-Dawley rats that either exercised regularly for 6 weeks or performed a single bout of exercise. Results A single exercise session improved endothelium-dependent vasodilatation for about 48 h. Six weeks of regular exercise induced a significantly larger improvement that lasted for about 192 h. Sensitivity to acetylcholine was twofold higher in chronically trained animals than in those exposed to a single bout of exercise. The decay after a single bout of exercise was about eightfold faster than that after 6 weeks of training. Conclusion The present data extend our concept of exercise-induced adaptation of endothelium-dependent vasodilatation in two regards: (1) a single bout of exercise improves endothelium-dependent dilation for about 2 days, with peak effect after 12-24 h; (2) regular exercise further improves adaptation and increases the sensitivity to acetylcholine approximately fourfold, which slowly returns to sedentary levels within a week of detraining.

Increased Theta and Alpha EEG Activity During Nondirective Meditation

OBJECTIVES In recent years, there has been significant uptake of meditation and related relaxation techniques, as a means of alleviating stress and maintaining good health. Despite its popularity, little is known about the neural mechanisms by which meditation works, and there is a need for more rigorous investigations of the underlying neurobiology. Several electroencephalogram (EEG) studies have reported changes in spectral band frequencies during meditation inspired by techniques that focus on concentration, and in comparison much less has been reported on mindfulness and nondirective techniques that are proving to be just as popular. DESIGN The present study examined EEG changes during nondirective meditation. The investigational paradigm involved 20 minutes of acem meditation, where the subjects were asked to close their eyes and adopt their normal meditation technique, as well as a separate 20-minute quiet rest condition where the subjects were asked to close their eyes and sit quietly in a state of rest. Both conditions were completed in the same experimental session with a 15-minute break in between. RESULTS Significantly increased theta power was found for the meditation condition when averaged across all brain regions. On closer examination, it was found that theta was significantly greater in the frontal and temporal-central regions as compared to the posterior region. There was also a significant increase in alpha power in the meditation condition compared to the rest condition, when averaged across all brain regions, and it was found that alpha was significantly greater in the posterior region as compared to the frontal region. CONCLUSIONS These findings from this study suggest that nondirective meditation techniques alter theta and alpha EEG patterns significantly more than regular relaxation, in a manner that is perhaps similar to methods based on mindfulness or concentration.

Aerobic Fitness Is Associated With Cardiomyocyte Contractile Capacity and Endothelial Function in Exercise Training and Detraining

Background—Physical fitness and level of regular exercise are closely related to cardiovascular health. A regimen of regular intensity-controlled treadmill exercise was implemented and withdrawn to identify cellular mechanisms associated with exercise capacity and maximal oxygen uptake (&OV0312;2max). Methods and Results—Time-dependent associations between cardiomyocyte dimensions, contractile capacity, and &OV0312;2max were assessed in adult rats after high-level intensity-controlled treadmill running for 2, 4, 8, and 13 weeks and detraining for 2 and 4 weeks. With training, cardiomyocyte length, relaxation, shortening, Ca2+ decay, and estimated cell volume correlated with increased &OV0312;2max (r =0.92, −0.92, 0.88, −0.84, 0.73; P <0.01). Multiple regression analysis identified cell length, relaxation, and Ca2+ decay as the main explanatory variables for V O2max (R2 =0.87, P <0.02). When training stopped, exercise-gained &OV0312;2max decreased 50% within 2 weeks and stabilized at 5% above sedentary controls after 4 weeks. Cardiomyocyte size regressed in parallel with &OV0312;2max and remained (9%) above sedentary after 4 weeks, whereas cardiomyocyte shortening, contraction/relaxation- and Ca2+ ransient time courses, and endothelium-dependent vasorelaxation regressed completely within 2 to 4 weeks of detraining. Cardiomyocyte length, estimated cell volume, width, shortening, and Ca2+decay and endothelium-dependent arterial relaxation all correlated with &OV0312;2max (r =.85, 0.84, 0.75, 0.63, −0.54, −0.37; P <0.01). Multiple regression identified cardiomyocyte length and vasorelaxation as the main determinants for regressed &OV0312;2max during detraining (R2 =0.76, P =0.02). Conclusions—Cardiovascular adaptation to regular exercise is highly dynamic. On detraining, most of the exercise-gained aerobic fitness acquired over 2 to 3 months is lost within 2 to 4 weeks. The close association between cardiomyocyte dimensions, contractile capacity, arterial relaxation, and aerobic fitness suggests cellular mechanisms underlying these changes.