Different protocols of physical exercise produce different effects on synaptic and structural proteins in motor areas of the rat brain

The plastic brain responses generated by the training with acrobatic exercise (AE) and with treadmill exercise (TE) may be different. We evaluated the protein expression of synapsin I (SYS), synaptophysin (SYP), microtubule-associated protein 2 (MAP2) and neurofilaments (NF) by immunohistochemistry and Western blotting in the motor cortex, striatum and cerebellum of rats subjected to TE and AE. Young adult male Wistar rats were divided into 3 groups: sedentary (Sed) (n=15), TE (n=20) and AE (n=20). The rats were trained 3 days/week for 4 weeks on a treadmill at 0.6 km/h, 40 min/day (TE), or moved through a circuit of obstacles 5 times/day (AE). The rats from the TE group exhibited a significant increase of SYS and SYP in the motor cortex, of NF68, SYS and SYP in the striatum, and of MAP2, NF and SYS in the cerebellum, whereas NF was decreased in the motor cortex and the molecular layer of the cerebellar cortex. On the other hand, the rats from the AE group showed a significant increase of MAP2 and SYP in the motor cortex, of all four proteins in the striatum, and of SYS in the cerebellum. In conclusion, AE induced changes in the expression of synaptic and structural proteins mainly in the motor cortex and striatum, which may underlie part of the learning of complex motor tasks. TE, on the other hand, promoted more robust changes of structural proteins in all three regions, especially in the cerebellum, which is involved in learned and automatic tasks. (C) 2012 Elsevier B.V. All rights reserved.

Age-Related Maximum Heart Rate Among Ischemic and Nonischemic Heart Failure Patients Receiving beta-Blockade Therapy

Background: Equations to predict maximum heart rate (HRmax) in heart failure (HF) patients receiving beta-adrenergic blocking (BB) agents do not consider the cause of HF. We determined equations to predict HRmax in patients with ischemic and nonischemic HF receiving BB therapy. Methods and Results: Using treadmill cardiopulmonary exercise testing, we studied HF patients receiving BB therapy being considered for transplantation from 1999 to 2010. Exclusions were pacemaker and/or implantable defibrillator, left ventricle ejection fraction (LVEF) >50%, peak respiratory exchange ratio (RER) <1.00, and Chagas disease. We used linear regression equations to predict HRmax based on age in ischemic and nonischemic patients. We analyzed 278 patients, aged 47 +/- 10 years, with ischemic (n = 75) and nonischemic (n = 203) HF. LVEF was 30.8 +/- 9.4% and 28.6 +/- 8.2% (P = .04), peak VO2 16.9 +/- 4.7 and 16.9 +/- 5.2 mL kg(-1) min(-1) (P = NS), and the HRmax 130.8 +/- 23.3 and 125.3 +/- 25.3 beats/min (P = .051) in ischemic and nonischemic patients, respectively. We devised the equation HRmax = 168 - 0.76 x age (R-2 = 0.095; P = .007) for ischemic HF patients, but there was no significant relationship between age and HRmax in nonischemic HF patients (R-2 = 0.006; P = NS). Conclusions: Our study suggests that equations to estimate HRmax should consider the cause of HF. (J Cardiac Fail 2012;18:831-836)

Association between muscle strength and the cardiopulmonary status of individuals living with HIV/AIDS

OBJECTIVE: The purpose of this study was to compare aerobic function [anaerobic threshold (%_VVO2-AT), respiratory compensation point (%_VVO2-RCP) and peak oxygen uptake (_VVO2peak)] between physically active patients with HIV/AIDS and matched controls and to examine associations between disease status, poor muscle strength, depression (as estimated by the profile of mood states questionnaire) and the aerobic performance of patients. METHODS: Progressive treadmill test data for %_VVO2-AT (V-slope method), RCP and (_VVO2peak) were compared between 39 male patients with HIV/AIDS (age 40.6¡1.4 years) and 28 male controls (age 44.4¡2.1 years) drawn from the same community and matched for habitual physical activity. Within-patient data were also examined in relation to CD4+ counts (nadir and current data) and peak isokinetic knee torque. RESULTS: AT, RCP and (_VVO2peak) values were generally similar for patients and controls.Within the patient sample, binary classification suggested that AT, RCP and (_VVO2peak) values were not associated with either the nadir or current CD4+ count, but treadmill test variables were positively associated with peak isokinetic knee torque. CONCLUSION: The aerobic performance of physically active patients with HIV/AIDS is generally well conserved. Nevertheless, poor muscle strength is observed in some HIV/AIDS patients, which is associated with lower anaerobic power and (_VVO2peak), suggesting the possibility of enhancing the aerobic performance of patients with weak muscles through appropriate muscle-strengthening activities.

AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC

Activators of 5'-AMP-activated protein kinase (AMPK) 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), metformin, and exercise activate atypical protein kinase C (aPKC) and ERK and stimulate glucose transport in muscle by uncertain mechanisms. Here, in cultured L6 myotubes: AICAR- and metformin-induced activation of AMPK was required for activation of aPKC and ERK; aPKC activation involved and required phosphoinositide-dependent kinase 1 (PDK1) phosphorylation of Thr410-PKC-zeta; aPKC Thr410 phosphorylation and activation also required MEK1-dependent ERK; and glucose transport effects of AICAR and metformin were inhibited by expression of dominant-negative AMPK, kinase-inactive PDK1, MEK1 inhibitors, kinase-inactive PKC-zeta, and RNA interference (RNAi)-mediated knockdown of PKC-zeta. In mice, muscle-specific aPKC (PKC-lambda) depletion by conditional gene targeting impaired AICAR-stimulated glucose disposal and stimulatory effects of both AICAR and metformin on 2-deoxyglucose/glucose uptake in muscle in vivo and AICAR stimulation of 2-[(3)H]deoxyglucose uptake in isolated extensor digitorum longus muscle; however, AMPK activation was unimpaired. In marked contrast to AICAR and metformin, treadmill exercise-induced stimulation of 2-deoxyglucose/glucose uptake was not inhibited in aPKC-knockout mice. Finally, in intact rodents, AICAR and metformin activated aPKC in muscle, but not in liver, despite activating AMPK in both tissues. The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin- and AICAR-stimulated increases in glucose transport. On the other hand, although aPKC is activated by treadmill exercise, this activation is not required for exercise-induced increases in glucose transport, and therefore may be a redundant mechanism.

Exercise-induced Growth Hormone Secretion in the Assessment of Growth Hormone Deficiency in Adult Individuals

The role of exercise testing in the assessment of GH deficiency (GHD) in adult patients is currently unclear. This study aimed at evaluating the diagnostic value of exercise-induced GH levels in the detection of severe GHD in adult patients.

Impact of aerobic exercise capacity and procedure-related factors in lung cancer surgery

Over the past decades, major progress in patient selection, surgical techniques and anaesthetic management have largely contributed to improved outcome in lung cancer surgery. The purpose of this study was to identify predictors of post-operative cardiopulmonary morbidity in patients with a forced expiratory volume in 1 s <80% predicted, who underwent cardiopulmonary exercise testing (CPET). In this observational study, 210 consecutive patients with lung cancer underwent CPET with completed data over a 9-yr period (2001-2009). Cardiopulmonary complications occurred in 46 (22%) patients, including four (1.9%) deaths. On logistic regression analysis, peak oxygen uptake (peak V'(O₂) and anaesthesia duration were independent risk factors of both cardiovascular and pulmonary complications; age and the extent of lung resection were additional predictors of cardiovascular complications, whereas tidal volume during one-lung ventilation was a predictor of pulmonary complications. Compared with patients with peak V'(O₂) >17 mL·kg⁻¹·min⁻¹, those with a peak V'(O₂) <10 mL·kg⁻¹·min⁻¹ had a four-fold higher incidence of cardiac and pulmonary morbidity. Our data support the use of pre-operative CPET and the application of an intra-operative protective ventilation strategy. Further studies should evaluate whether pre-operative physical training can improve post-operative outcome.

Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease

OBJECTIVES: To assess the safety and cardiopulmonary adaptation to high altitude exposure among patients with coronary artery disease. METHODS: 22 patients (20 men and 2 women), mean age 57 (SD 7) years, underwent a maximal, symptom limited exercise stress test in Bern, Switzerland (540 m) and after a rapid ascent to the Jungfraujoch (3454 m). The study population comprised 15 patients after ST elevation myocardial infarction and 7 after a non-ST elevation myocardial infarction 12 (SD 4) months after the acute event. All patients were revascularised either by percutaneous coronary angioplasty (n = 15) or by coronary artery bypass surgery (n = 7). Ejection fraction was 60 (SD 8)%. beta blocking agents were withheld for five days before exercise testing. RESULTS: At 3454 m, peak oxygen uptake decreased by 19% (p < 0.001), maximum work capacity by 15% (p < 0.001) and exercise time by 16% (p < 0.001); heart rate, ventilation and lactate were significantly higher at every level of exercise, except at maximum exertion. No ECG signs of myocardial ischaemia or significant arrhythmias were noted. CONCLUSIONS: Although oxygen demand and lactate concentrations are higher during exercise at high altitude, a rapid ascent and submaximal exercise can be considered safe at an altitude of 3454 m for low risk patients six months after revascularisation for an acute coronary event and a normal exercise stress test at low altitude.

[Suddenly occurring exercise intolerance]

In this case report, the differencial diagnosis of exercise intolerance associated with dyspnea and the diagnostic approach with cardio-pulmonary exercise testing with detection of an exercise induced second-degree atrio-ventricular block as a cause of chronotropic incompetence is described.

Heart rate recovery after exercise in chronic heart failure: Role of vital exhaustion and type D personality

OBJECTIVE: Vital exhaustion and type D personality previously predicted mortality and cardiac events in patients with chronic heart failure (CHF). Reduced heart rate recovery (HRR) also predicts morbidity and mortality in CHF. We hypothesized that elevated levels of vital exhaustion and type D personality are both associated with decreased HRR. METHODS: Fifty-one patients with CHF (mean age 58+/-12 years, 82% men) and left ventricular ejection fraction (LVEF) exercise testing before receiving outpatient cardiac rehabilitation. They completed the 9-item short form of the Maastricht Vital Exhaustion Questionnaire and the 14-item type D questionnaire asking about negative affectivity and social inhibition. HRR was calculated as the difference between heart rate at the end of exercise and 1min after abrupt cessation of exercise (HRR-1). Regression analyses were adjusted for gender, age, LVEF, and maximum exercise capacity. RESULTS: Vital exhaustion explained 8.4% of the variance in continuous HRR-1 (p=0.045). For each point increase on the vital exhaustion score (range 0-18) there was a mean+/-SEM decrease of 0.54+/-0.26bpm in HRR-1. Type D personality showed a trend toward statistical significance for being associated with lower levels of HRR-1 explaining 6.5% of the variance (p<0.08). The likelihood of having HRR-1

Effects of weight on blood pressure at rest and during exercise.

Body weight (BW) and blood pressure (BP) have a close relationship, which has been accounted for by hormonal changes. No previous study has evaluated the effect of wearing an external weight vest on BP to determine whether there is a simple mechanism between BW and BP. Seventeen healthy volunteers underwent weight reduction (WR) through caloric restriction. Before and after WR, BW, body fat percentage and BP at rest and during exercise were measured. Before and after WR, exercise testing was performed twice with the random allocation of a weight vest (10 kg) during one of the tests. Linear regression was used to detect independent associations between BP and the weight vest, BW and body fat percentage. BW decreased from 89.4 ± 15.4 kg to 79.1 ± 14.0 kg following WR (P<0.001). WR led to significant decreases in BP at rest (from 130.0/85.9 mm Hg to 112.5/77.8 mm Hg, P<0.001 for systolic and diastolic BPs) and during exercise. The weight vest significantly increased BP at rest (to 136.1/90.7 mm Hg before and 125.8/84.6 mm Hg after WR) and during exercise. Linear regression analysis identified an independent association between the weight vest and BP (P=0.006 for systolic BP and P=0.009 for diastolic BP at rest). This study demonstrates that wearing an external weight vest has immediate effects on BP at rest and during exercise independent of BW or body fat. More research is needed to understand the physiological mechanisms between weight and BP.

The impact of antioxidant supplements and endurance exercise on genes of the carbohydrate and lipid metabolism in skeletal muscle of mice

To ascertain whether reactive oxygen species (ROS) contribute to training-induced adaptation of skeletal muscle, we administered ROS-scavenging antioxidants (AOX; 140 mg/l of ascorbic acid, 12 mg/l of coenzyme Q10 and 1% N-acetyl-cysteine) via drinking water to 16 C57BL/6 mice. Sixteen other mice received unadulterated tap water (CON). One cohort of both groups (CON(EXE) and AOX(EXE) ) was subjected to treadmill exercise for 4 weeks (16-26 m/min, incline of 5°-10°). The other two cohorts (CON(SED) and AOX(SED) ) remained sedentary. In skeletal muscles of the AOX(EXE) mice, GSSG and the expression levels of SOD-1 and PRDX-6 were significantly lower than those in the CON(EXE) mice after training, suggesting disturbance of ROS levels. The peak power related to the body weight and citrate synthase activity was not significantly influenced in mice receiving AOX. Supplementation with AOX significantly altered the mRNA levels of the exercise-sensitive genes HK-II, GLUT-4 and SREBF-1c and the regulator gene PGC-1alpha but not G6PDH, glycogenin, FABP-3, MCAD and CD36 in skeletal muscle. Although the administration of AOX during endurance exercise alters the expression of particular genes of the ROS metabolism, it does not influence peak power or generally shift the metabolism, but it modulates the expression of specific genes of the carbohydrate and lipid metabolism and PGC-1alpha within murine skeletal muscle.

Effect of carbohydrate supplementation on walking performance in peripheral arterial disease: A preliminary physiologic study

Objective: In this preliminary study we tested the effect of short-term carbohydrate supplementation on carbohydrate oxidation and walking performance in peripheral arterial disease. Methods: Eleven patients with peripheral arterial disease and intermittent claudication and 8 healthy control subjects completed several weeks of baseline exercise testing, then were given supplementation for 3 days with a carbohydrate solution and placebo. Maximal walking time was assessed with a graded treadmill test. Carbohydrate oxidation during a submaximal phase of this test was measured with indirect calorimetry. At the end of baseline testing a biopsy specimen was taken from the gastrocnemius muscle, and the active fraction of pyruvate dehydrogenase complex activity was determined. Results: Carbohydrate supplementation resulted in a significant increase in body weight and carbohydrate oxidation during exercise in patients with intermittent claudication and control subjects. Maximal walking time decreased by 3% in control subjects, whereas it increased by 6% in patients with intermittent claudication (group X treatment interaction, P < .05). There was a wide range of performance responses to carbohydrate supplementation among patients with claudication (-3%-37%). This effect was greater in poorer performers, and was negatively correlated (P < .05) with muscle pyruvate dehydrogenase complex activity. Conclusion: Preliminary data suggest that carbohydrate oxidation during exercise might contribute to exercise intolerance in more dysfunctional patients with intermittent claudication and that carbohydrate supplementation might be an effective therapeutic intervention in these patients.

Determinants of exercise capacity in patients with type 2 diabetes

OBJECTIVE - Type 2 diabetes is associated with reduced exercise capacity, but the cause of this association is unclear. We sought the associations of impaired exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS - Subclinical left ventricular (LV) dysfunction was sought from myocardial strain rate and the basal segmental diastolic velocity (Em) of each wall in 170 patients with type 2 diabetes (aged 56 +/- 10 years, 91 men), good quality echocardiographic images, and negative exercise echocardiograms. The same measurements were made in 56 control subjects (aged 53 +/- 10 years, 29 men). Exercise capacity was calculated in metabolic equivalents, and heart rate recovery (HRR) was measured as the heart rate difference between peak and 1 min after exercise. In subjects with type 2 diabetes, exercise capacity was correlated with clinical, therapeutic, biochemical, and echocardiographic variables, and significant independent associations were sought using a multiple linear regression model. RESULTS - Exercise capacity, strain rate, Em, and HRR were significantly reduced in type 2 diabetes. Exercise capacity was associated with age (r- = -0.37, P < 0.001), male sex (r = 0.26, P = 0.001), BMI (r = -0.19, P = 0.012), HbA(1c) (AlC; r = -0.22, P = 0.009), Em (r = 0.43, P < 0.001), HRR (r = 0.42, P < 0.001), diabetes duration (r = -0.18, P = 0.021), and hypertension history (r = -0.28, P < 0.001). Age (P < 0.001), male sex (P = 0.007), BMI (P = 0.001), Em (P = 0.032), HRR (P = 0.013), and AlC (P = 0.0007) were independent predictors of exercise capacity. CONCLUSIONS - Reduced exercise capacity in patients with type 2 diabetes is associated with diabetes control, subclinical LV dysfunction, and impaired HRR.

Impact of gender on risk stratification by exercise and dobutamine stress echocardiography: long-term mortality in 4234 women and 6898 men

Aims Prior research is limited with regard to the diagnostic and prognostic accuracy of commonplace cardiac imaging modalities in women. The aim of this study was to examine 5-year mortality in 4234 women and 6898 men undergoing exercise or dobutamine stress echocardiography at three hospitals. Methods and results Univariable and multivariable Cox proportional hazards models were used to estimate time to cardiac death in this multi-centre, observational registry. Of the 11 132 patients, women had a greater frequency of cardiac risk factors (P < 0.0001). However, men more often had a history of coronary disease including a greater frequency of echocardiographic wall motion abnormalities (P < 0.0001). During 5 years of follow-up, 103 women and 226 men died from ischaernic heart disease (P < 0.0001). Echocardiographic estimates of left ventricular function (P < 0.0001) and the extent of ischaernic watt motion abnormalities (P < 0.0001) were highly predictive of cardiac death. Risk-adjusted 5-year survival was 99.4, 97.6, and 95% for exercising women with no, single, and multi-vessel ischaemia (P < 0.0001). For women undergoing dobutamine stress, 5-year survival was 95, 89, and 86.6% for those with 0, 1, and 2-3 vessel ischaemia (P < 0.0001). Exercising men had a 2.0-fold higher risk at every level of worsening ischaemia (P < 0.0001). Significantly worsening cardiac survival was noted for the 1568 men undergoing dobutamine stress echocardiography (P < 0.0001); no ischaemia was associated with 92% 5-year survival as compared with death rates of &GE; 16% for men with ischaemia on dobutamine stress echocardiography (P < 0.0001). Conclusion Echocardiographic measures of inducible wall motion abnormalities and global and regional left ventricutar function are highly predictive of long-term outcome for women and men alike.

Is exercise good for you?

Physical activity can significantly reduce the risk of cardiovascular disease, diabetes, some forms of cancer, osteoporosis, obesity, falls and fractures, and some mental health problems. While the benefits of physical activity are clear, there is a slightly increased risk of sudden death while exercising (compared with while sedentary), especially in untrained people undertaking unaccustomed vigorous activity. Routine exercise testing yields a significant number of false-positive results, and has not been shown to prevent exercise-related acute cardiac events. There is no convincing evidence that exercise is itself associated with osteoarthritis, but significant joint injury which occurs during sport is associated with an increased risk of subsequent development of osteoarthritis.