Bruno M. Silva

Neural Regulation of Cardiovascular Response to Exercise: Role of Central Command and Peripheral Afferents

During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discussed.

Remote ischemic preconditioning delays fatigue development during handgrip exercise

Ischemic preconditioning (IPC) of one or two limbs improves performance of exercise that recruits the same limb(s). However, it is unclear whether IPC application to another limb than that in exercise is also effective and which mechanisms are involved. We investigated the effect of remote IPC (RIPC) on muscle fatigue, time to task failure, forearm hemodynamics, and deoxygenation during handgrip exercise. Thirteen men underwent RIPC in the lower limbs or a control intervention (CON), in random order, and then performed a constant load rhythmic handgrip protocol until task failure. Rates of contraction and relaxation (ΔForce/ΔTime) were used as indices of fatigue. Brachial artery blood flow and conductance, besides forearm microvascular deoxygenation, were assessed during exercise. RIPC attenuated the slowing of contraction and relaxation throughout exercise (P < 0.05 vs CON) and increased time to task failure by 11.2% (95% confidence interval: 0.7–21.7%, P <0.05 vs CON). There was no significant difference in blood flow, conductance, and deoxygenation between conditions throughout exercise (P > 0.05). In conclusion, RIPC applied to the lower limbs delayed the development of fatigue during handgrip exercise, prolonged time to task failure, but was not accompanied by changes in forearm hemodynamics and deoxygenation.

Nutritional status is related to fat-free mass, exercise capacity and inspiratory strength in severe chronic obstructive pulmonary disease patients

INTRODUCTION: Being overweight or obese is associated with a higher rate of survival in patients with advanced chronic obstructive pulmonary disease (COPD). This paradoxical relationship indicates that the influence of nutritional status on functional parameters should be further investigated. OBJECTIVE: To investigate the impact of nutritional status on body composition, exercise capacity and respiratory muscle strength in severe chronic obstructive pulmonary disease patients. METHODS: Thirty-two patients (nine women) were divided into three groups according to their body mass indices (BMI): overweight/obese (25 ≤ BMI ≤ 34.9 kg/m2, n=8), normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2, n=17) and underweight (BMI <18.5 kg/m2, n=7). Spirometry, bioelectrical impedance, a six-minute walking distance test and maximal inspiratory and expiratory pressures were assessed. RESULTS: Airway obstruction was similar among the groups (p=0.30); however, overweight/obese patients had a higher fat-free mass (FFM) index [FFMI=FFM/body weight2 (mean±SEM: 17±0.3 vs. 15±0.3 vs. 14±0.5 m/kg2, p<0.01)], exercise capacity (90±8 vs. 79±6 vs. 57±8 m, p=0.02) and maximal inspiratory pressure (63±7 vs. 57±5 vs. 35±8 % predicted, p=0.03) in comparison to normal weight and underweight patients, respectively. In addition, on backward multiple regression analysis, FFMI was the unique independent predictor of exercise capacity (partial r=0.52, p<0.01). CONCLUSIONS: Severe chronic obstructive pulmonary disease (COPD) patients who were overweight or obese had a greater FFM, exercise capacity and inspiratory muscle strength than patients with the same degree of airflow obstruction who were of normal weight or underweight, and higher FFM was independently associated with higher exercise capacity. These characteristics of overweight or obese patients might counteract the drawbacks of excess weight and lead to an improved prognosis in COPD.

Ischemic Preconditioning and Repeated Sprint Swimming: A Placebo and Nocebo Study.

PURPOSE Ischemic preconditioning (IPC) has been shown to improve performance of exercises lasting 10-90 s (anaerobic) and more than 90 s (aerobic). However, its effect on repeated sprint performance has been controversial, placebo effect has not been adequately controlled, and nocebo effect has not been avoided. Thus, the IPC effect on repeated sprint performance was investigated using a swimming task and controlling placebo/nocebo effects. METHODS Short-distance university swimmers were randomized to two groups. One group (n = 15, 24 ± 1 yr [mean ± SEM]) was exposed to IPC (ischemia cycles lasted 5 min) and control (CT) (no ischemia); another (n = 15, 24 ± 1 yr) to a placebo intervention (SHAM) (ischemia cycles lasted 1 min) and CT. Seven subjects crossed over groups. Subjects were informed IPC and SHAM would improve performance compared with CT and would be harmless despite circulatory occlusion sensations. The swimming task consisted of six 50-m all-out efforts repeated every 3 min. RESULTS IPC, in contrast with SHAM, reduced worst sprint time (IPC, 35.21 ± 0.73 vs CT, 36.53 ± 0.72 s; P = 0.04) and total sprints time (IPC, 203.7 ± 4.60 vs CT, 206.03 ± 4.57 s; P = 0.02), moreover augmented swimming velocity (IPC, 1.45 ± 0.03 vs CT, 1.44 ± 0.03 m·s; P = 0.049). Six of seven subjects who crossed over groups reduced total sprints time with IPC versus SHAM (delta = -3.95 ± 1.49 s, P = 0.09). Both IPC and SHAM did not change blood lactate concentration (P = 0.20) and perceived effort (P = 0.22). CONCLUSION IPC enhanced repeated sprint swimming performance in university swimmers, whereas a placebo intervention did not.

Preserved flow-mediated dilation but delayed time-to-peak diameter in individuals with metabolic syndrome.

Inconsistent evidences of the metabolic syndrome (MetS) impact on vascular reactivity raise questions on flow‐mediated dilation (FMD) discriminatory power for disturbances induced by this clustering of risk factors. Previous reports, however, suggest that covariates such as the follow‐up of the artery diameter changes, the arterial size and shear stress affect FMD responses and consequently its discriminatory power for distinctive clinical profiles.

Sildenafil improves skeletal muscle oxygenation during exercise in men with intermittent claudication

Endothelial dysfunction caused by defective nitric oxide (NO) signaling plays a pivotal role in the pathogenesis of intermittent claudication (IC). In the present study, we evaluated the acute effects of sildenafil, a phosphodiesterase type 5 inhibitor that acts by prolonging NO-mediated cGMP signaling in vascular smooth muscle, on blood pressure (BP), skeletal muscle oxygenation, and walking tolerance in patients with IC. A randomized, double-blind, crossover study was conducted in which 12 men with stable IC received two consecutive doses of 50 mg of sildenafil or matching placebo and underwent a symptom-limited exercise test on the treadmill. Changes in gastrocnemius deoxy-hemoglobin by near-infrared spectroscopy estimated peripheral muscle O2 delivery-to-utilization matching. Systolic BP was significantly lower during the sildenafil trial relative to placebo during supine rest (∼15 mmHg), submaximal exercise (∼14 mmHg), and throughout recovery (∼18 mmHg) (P < 0.05). Diastolic BP was also lower after sildenafil during upright rest (∼6 mmHg) and during recovery from exercise (∼7 mmHg) (P < 0.05). Gastrocnemius deoxygenation was consistently reduced during submaximal exercise (∼41%) and at peak exercise (∼34%) following sildenafil compared with placebo (P < 0.05). However, pain-free walking time (placebo: 335 ± 42 s vs. sildenafil: 294 ± 35 s) and maximal walking time (placebo: 701 ± 58 s vs. sildenafil: 716 ± 62 s) did not differ between trials. Acute administration of sildenafil lowers BP and improves skeletal muscle oxygenation during exercise but does not enhance walking tolerance in patients with IC. Whether the beneficial effects of sildenafil on muscle oxygenation can be sustained over time and translated into positive clinical outcomes deserve further consideration in this patient population.

Impaired hemodynamic response to mental stress in subjects with prehypertension is improved after a single bout of maximal dynamic exercise

INTRODUCTION: High blood pressure during mental stress in subjects with prehypertension is associated with blunted vasodilation in skeletal muscles, which might be improved by an acute bout of exercise. OBJECTIVE: To investigate the hemodynamic responses to mental stress before and after a bout of exercise in subjects with prehypertension. METHOD: Eighteen subjects with prehypertension and 16 with normotension underwent a mental stress test before and after a maximal cardiopulmonary exercise test on a treadmill. Blood pressure was measured by auscultation, and forearm blood flow was measured by venous occlusion plethysmography; from these measurements, the vascular conductance was calculated. RESULTS: Subjects with prehypertension had a higher mean blood pressure during mental stress (prehypertension 112±2 vs. normotension 101±3 mm Hg, p<0.05), and their vascular conductance did not increase (baseline 0.025±0.004 vs. mental stress 0.022±0.003 a.u., p>0.05). After the exercise bout, the mean blood pressure during mental stress was lower in subjects with prehypertension (before exercise 112±2 vs. after exercise 107±2 mm Hg, p<0.05), and vascular conductance increased (baseline 0.011±0.001 vs. mental stress 0.024±0.004 a.u., p<0.05). CONCLUSION: Subjects with prehypertension had elevated blood pressure and a blunted vasodilator response during mental stress, but their blood pressure was attenuated and their vasodilator response was normalized after a single bout of maximal dynamic exercise.

Effect of Ischemic Preconditioning on Endurance Performance Does Not Surpass Placebo

Purpose Recent studies have reported ischemic preconditioning (IPC) can acutely improve endurance exercise performance in athletes. However, placebo and nocebo effects have not been sufficiently controlled, and the effect on aerobic metabolism parameters that determine endurance performance (e.g., oxygen cost of running, lactate threshold, and maximal oxygen uptake [V˙O2max]) has been equivocal. Thus, we circumvented limitations from previous studies to test the effect of IPC on aerobic metabolism parameters and endurance performance in well-trained runners. Methods Eighteen runners (14 men/4 women) were submitted to three interventions, in random order: IPC; sham intervention (SHAM); and resting control (CT). Subjects were told both IPC and SHAM would improve performance compared to CT (i.e., similar placebo induction), and IPC would be harmless despite circulatory occlusion sensations (i.e., nocebo avoidance). Next, pulmonary ventilation and gas exchange, blood lactate concentration, and perceived effort were measured during a discontinuous incremental test on a treadmill. Then, a supramaximal test was used to verify the V˙O2max and assess endurance performance (i.e., time to exhaustion). Results Ventilation, oxygen uptake, carbon dioxide output, lactate concentration, and perceived effort were similar among IPC, SHAM, and CT throughout the discontinuous incremental test (P > 0.05). Oxygen cost of running, lactate threshold, and V˙O2max were also similar among interventions (P > 0.05). Time to exhaustion was longer after IPC (mean ± SEM, 165.34 ± 12.34 s) and SHAM (164.38 ± 11.71 s) than CT (143.98 ± 12.09 s; P = 0.02 and 0.03, respectively), but similar between IPC and SHAM (P = 1.00). Conclusions IPC did not change aerobic metabolism parameters, whereas improved endurance performance. The IPC improvement, however, did not surpass the effect of a placebo intervention.

Aerobic exercise acutely prevents the endothelial dysfunction induced by mental stress among subjects with metabolic syndrome: the role of shear rate

Mental stress induces transient endothelial dysfunction, which is an important finding for subjects at cardiometabolic risk. Thus, we tested whether aerobic exercise prevents this dysfunction among subjects with metabolic syndrome (MetS) and whether an increase in shear rate during exercise plays a role in this phenomenon. Subjects with MetS participated in two protocols. In protocol 1 (n = 16), endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Subjects then underwent a mental stress test followed by either 40 min of leg cycling or rest across two randomized sessions. FMD was assessed again at 30 and 60 min after exercise or rest, with a second mental stress test in between. Mental stress reduced FMD at 30 and 60 min after the rest session (baseline: 7.7 ± 0.4%, 30 min: 5.4 ± 0.5%, and 60 min: 3.9 ± 0.5%, P < 0.05 vs. baseline), whereas exercise prevented this reduction (baseline: 7.5 ± 0.4%, 30 min: 7.2 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline). Protocol 2 (n = 5) was similar to protocol 1 except that the first period of mental stress was followed by either exercise in which the brachial artery shear rate was attenuated via forearm cuff inflation or exercise without a cuff. Noncuffed exercise prevented the reduction in FMD (baseline: 7.5 ± 0.7%, 30 min: 7.0 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline), whereas cuffed exercise failed to prevent this reduction (baseline: 7.5 ± 0.6%, 30 min: 5.4 ± 0.8%, and 60 min: 4.1 ± 0.9%, P < 0.05 vs. baseline). In conclusion, exercise prevented mental stress-induced endothelial dysfunction among subjects with MetS, and an increase in shear rate during exercise mediated this effect.

Endothelial nitric oxide synthase polymorphisms and adaptation of parasympathetic modulation to exercise training.

PURPOSE There is a large interindividual variation in the parasympathetic adaptation induced by aerobic exercise training, which may be partially attributed to genetic polymorphisms. Therefore, we investigated the association among three polymorphisms in the endothelial nitric oxide gene (-786T>C, 4b4a, and 894G>T), analyzed individually and as haplotypes, and the parasympathetic adaptation induced by exercise training. METHODS Eighty healthy males, age 20-35 yr, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis, and haplotypes were inferred using the software PHASE 2.1. Autonomic modulation (i.e., HR variability and spontaneous baroreflex sensitivity) and peak oxygen consumption (VO(2peak)) were measured before and after training (running, moderate to severe intensity, three times per week, 60 min·day(-1), during 18 wk). RESULTS Training increased VO(2peak) (P < 0.05) and decreased mean arterial pressure (P < 0.05) in the whole sample. Subjects with the -786C polymorphic allele had a significant reduction in baroreflex sensitivity after training (change: wild type (-786TT) = 2% ± 89% vs polymorphic (-786TC/CC) = -28% ± 60%, median ± quartile range, P = 0.03), and parasympathetic modulation was marginally reduced in subjects with the 894T polymorphic allele (change: wild type (894GG) = 8% ± 67% vs polymorphic (894GT/TT) = -18% ± 59%, median ± quartile range, P = 0.06). Furthermore, parasympathetic modulation percent change was different between the haplotypes containing wild-type alleles (-786T/4b/894G) and polymorphic alleles at positions -786 and 894 (-786C/4b/894T) (-6% ± 56% vs -41% ± 50%, median ± quartile range, P = 0.04). CONCLUSIONS The polymorphic allele at position -786 and the haplotype containing polymorphic alleles at positions -786 and 894 in the endothelial nitric oxide gene were associated with decreased parasympathetic modulation after exercise training.