Per Magnus Haram

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.

Aerobic Interval Training Versus Continuous Moderate Exercise as a Treatment for the Metabolic Syndrome A Pilot Study

Background— Individuals with the metabolic syndrome are 3 times more likely to die of heart disease than healthy counterparts. Exercise training reduces several of the symptoms of the syndrome, but the exercise intensity that yields the maximal beneficial adaptations is in dispute. We compared moderate and high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with the metabolic syndrome. Methods and Results— Thirty-two metabolic syndrome patients (age, 52.3±3.7 years; maximal oxygen uptake [&OV0312;o2max], 34 mL · kg−1 · min−1) were randomized to equal volumes of either moderate continuous moderate exercise (CME; 70% of highest measured heart rate [Hfmax]) or aerobic interval training (AIT; 90% of Hfmax) 3 times a week for 16 weeks or to a control group. &OV0312;o2max increased more after AIT than CME (35% versus 16%; P<0.01) and was associated with removal of more risk factors that constitute the metabolic syndrome (number of factors: AIT, 5.9 before versus 4.0 after; P<0.01; CME, 5.7 before versus 5.0 after; group difference, P<0.05). AIT was superior to CME in enhancing endothelial function (9% versus 5%; P<0.001), insulin signaling in fat and skeletal muscle, skeletal muscle biogenesis, and excitation-contraction coupling and in reducing blood glucose and lipogenesis in adipose tissue. The 2 exercise programs were equally effective at lowering mean arterial blood pressure and reducing body weight (−2.3 and −3.6 kg in AIT and CME, respectively) and fat. Conclusions— Exercise intensity was an important factor for improving aerobic capacity and reversing the risk factors of the metabolic syndrome. These findings may have important implications for exercise training in rehabilitation programs and future studies.

Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity

AIMS The recent development of a rat model that closely resembles the metabolic syndrome allows to study the mechanisms of amelioration of the syndrome by exercise training. Here, we compared the effectiveness for reducing cardiovascular risk factors by exercise training programmes of different exercise intensities. METHODS AND RESULTS Metabolic syndrome rats were subjected to either continuous moderate-intensity exercise (CME) or high-intensity aerobic interval training (AIT). AIT was more effective than CME at reducing cardiovascular disease risk factors linked to the metabolic syndrome. Thus, AIT produced a larger stimulus than CME for increasing maximal oxygen uptake (VO(2max); 45 vs. 10%, P < 0.01), reducing hypertension (20 vs. 6 mmHg, P < 0.01), HDL cholesterol (25 vs. 0%, P < 0.05), and beneficially altering metabolism in fat, liver, and skeletal muscle tissues. Moreover, AIT had a greater beneficial effect than CME on sensitivity of aorta ring segments to acetylcholine (2.7- vs. 2.0-fold, P < 0.01), partly because of intensity-dependent effects on expression levels of nitric oxide synthase and the density of caveolae, and a greater effect than CME on the skeletal muscle Ca2+ handling (50 vs. 0%, P < 0.05). The two exercise training programmes, however, were equally effective at reducing body weight and fat content. CONCLUSION High-intensity exercise training was more beneficial than moderate-intensity exercise training for reducing cardiovascular risk in rats with the metabolic syndrome. This was linked to more superior effects on VO(2max), endothelial function, blood pressure, and metabolic parameters in several tissues. These results demonstrate that exercise training reduces the impact of the metabolic syndrome and that the magnitude of the effect depends on exercise intensity.

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.

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.

Endothelial function in highly endurance-trained men : effects of acute exercise.

Exercise training reverses endothelial dysfunction, but the effect in young, healthy subjects is less clear. We determined the influence of maximal oxygen uptake (&OV0312;o2max) and a single bout of high-intensity exercise on flow-mediated dilatation (FMD), brachial artery diameter, peak blood flow, nitric oxide (NO) bioavailability, and antioxidant status in highly endurance-trained men and their sedentary counterparts. Ten men athletes (mean ± SEM age 23.5 ± 0.9 years, height 182.6 ± 2.4 cm, weight 72.5 ± 2.4 kg, &OV0312;o2max 75.9 ± 0.8 mL·kg−1·min−1) and seven healthy controls (age 25.4 ± 1.2 years, height 183.9 ± 3.74 cm, weight 92.8 ± 3.9 kg, &OV0312;o2max 47.7 ± 1.7 mL·kg−1·min−1) took part in the study. FMD, brachial artery diameter, and peak blood flow were measured using echo-Doppler before, 1 hour, 24 hours, and 48 hours after a single bout of interval running for 5 × 5 minutes at 90% of maximal heart rate. NO bioavailability and antioxidant status in blood were measured at all time points. Maximal arterial diameter and peak flow were 10-15% (P < 0.02) and 28-35% (P < 0.02) larger, respectively, in athletes vs. controls at all time points, and similar FMD were observed, apart from a transient decay of FMD in athletes 1 hour post exercise. NO bioavailability increased significantly after exercise in both groups and decreased to baseline levels after 24 hours in controls but remained increased 80% and 93% above baseline 24 and 48 hours post exercise in athletes. Antioxidant status was equal in the two groups at baseline and increased by approximately 10% 1 hour post exercise, an effect that lasted for 24 hours. Athletes had larger arterial diameter but similar FMD as untrained subjects, i.e., athletes had larger capacity for blood transport compared with their untrained counterparts. The observed FMD, bioavailability of NO, and antioxidant status in blood were highly dependent on the time elapsed after the exercise session.

Adaptation of endothelium to exercise training: insights from experimental studies.

Endothelial dysfunction is one of the hallmarks of cardiovascular disease and serves as a prognostic marker for forecasting the development and outcome of the disease process. Current pharmacological treatment strategies only incompletely repair endothelial dysfunction whereas exercise training corrects this dysfunction, primarily due to improved production and/or bioavailability of nitric oxide, the main endothelium-derived vasodilator. This type of treatment also improves the function of healthy endothelium. The focus of this review is to discuss the underlying biological factors involved in improved endothelial function after exercise training in healthy individuals as well as those with cardiovascular disease or a metabolic syndrome. The ability to sustain the bioavailability of nitric oxide (NO) in the endothelium is probably the most important factor in restoring normal endothelial function by exercise training.

The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts

The response of transverse (T)‐tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T‐tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P < 0.01), with preserved T‐tubule density. Thus, the T‐tubules adapted to the physiologic hypertrophy. Next, we studied T‐tubules in a rat model of metabolic syndrome with pressure overload‐induced concentric left ventricle hypertrophy, evidenced by 15% (P < 0.01) increased cardiomyocyte size. These rats had only 85% (P < 0.01) of the T‐tubule density of control rats. Exercise training further increased cardiomyocyte volume by 8% (P < 0.01); half to that in control rats, but the T‐tubule density remained unchanged. Finally, post‐myocardial infarction heart failure induced severe cardiac pathology, with a 70% (P < 0.01) increased cardiomyocyte volume that included both eccentric and concentric hypertrophy and 55% (P < 0.01) reduced T‐tubule density. Exercise training reversed 50% (P < 0.01) of the pathologic hypertrophy, whereas the T‐tubule density increased by 40% (P < 0.05) compared to sedentary heart failure, but remained at 60% of normal hearts (P < 0.01). Physiologic hypertrophy associated with conserved T‐tubule spacing (∼1.8–1.9 µm), whereas in pathologic hypertrophy, T‐tubules appeared disorganized without regular spacing. In conclusion, cardiomyocytes maintain the relative T‐tubule density during physiologic hypertrophy and after mild concentric pathologic hypertrophy, whereas after severe pathologic remodeling with a substantial loss of T‐tubules; exercise training reverses the remodeling and partly corrects the T‐tubule density. J. Cell. Physiol. 226: 2235–2243, 2011.

Caloric Restriction Reverses Hepatic Insulin Resistance and Steatosis in Rats with Low Aerobic Capacity

Rats selectively bred for low aerobic running capacity exhibit the metabolic syndrome, including hyperinsulinemia, insulin resistance, visceral obesity, and dyslipidemia. They also exhibit features of nonalcoholic steatohepatitis, including chicken-wire fibrosis, inflammation, and oxidative stress. Hyperinsulinemia in these rats is associated with impaired hepatic insulin clearance. The current studies aimed to determine whether these metabolic abnormalities could be reversed by caloric restriction (CR). CR by 30% over a period of 2-3 months improved insulin clearance in parallel to inducing the protein content and activation of the carcinoembryonic antigen-related cell adhesion molecule 1, a main player in hepatic insulin extraction. It also reduced glucose and insulin intolerance and serum and tissue (liver and muscle) triglyceride levels. Additionally, CR reversed inflammation, oxidative stress, and fibrosis in liver. The data support a significant role of CR in the normalization of insulin and lipid metabolism in liver.

Exercise training and losartan improve endothelial function in heart failure rats by different mechanisms

Abstract Objectives. To investigate the mechanisms of losartan- and exercise training-induced improvements on endothelial dysfunction in heart failure. Design. Sprague-Dawley rats subjected to left coronary artery ligation inducing myocardial infarction and heart failure were randomized to losartan treatment, high-intensity exercise training, or both. Results. Losartan, but not exercise training, reduced the heart failure-associated elevation in left ventricular end-diastolic pressure (26 ± 2 mmHg vs. 19 ± 1 mmHg after losartan). In contrast, both exercise training and losartan improved exercise capacity, by 40% and 20%, respectively; no additional effects were observed when exercise training and losartan were combined. Aortic segments were mounted on a force transducer to determine vasorelaxation. Heart failure impaired endothelium-dependent vasorelaxation, observed as a 1.9-fold reduced response to acetylcholine (EC50). Exercise and losartan improved acetylcholine-mediated vasorelaxation to the same extent, but by different mechanisms. Exercise training upregulated the nitric oxide pathway, whereas losartan upregulated a non-nitric oxide or -prostacyclin pathway; possibly involving the endothelium-dependent hyperpolarizing factor. Conclusions. Both losartan and exercise training reversed endothelial dysfunction in heart failure; exercise training via nitric oxide-dependent vasorelaxation, and losartan via an unknown mechanism that may involve endothelium-dependent hyperpolarizing factor. Thus, the combined treatment activated an additional nitric oxide- independent mechanism that contributed to reduce endothelial dysfunction.