12-Week Exercise Training, Independent of the Type of Exercise, Attenuates Endothelial Ischaemia-Reperfusion Injury in Heart Failure Patients.

Introduction: Reperfusion is required to salvage ischaemic tissue, but also causes further damage (i.e., ischaemia/reperfusion-injury). Heart failure patients reveal exaggerated ischaemia/reperfusion-injury, whilst traditional ischaemic preconditioning cannot prevent ischaemia/reperfusion-injury. Exercise training may be a more powerful preconditioning stimulus, especially high-intensity interval training given the similarities with ischaemic preconditioning. Therefore, we examined the impact of 12-week continuous training vs. high-intensity interval training on brachial artery endothelial ischaemia/reperfusion-injury in heart failure patients New York Heart Association-class II-III. Methods: Twenty heart failure patients (male:female 19:1, 64 ± 8 years, ejection fraction 38 ± 6%) were allocated to 12-weeks of high-intensity interval training (10∗1-min 90% maximal workload - 2.5-min 30% maximal workload) or continuous training (30-min 60-75% maximal workload). Before and after the intervention, we measured brachial artery endothelial function with flow-mediated dilation (FMD) before and after ischaemia/reperfusion (5-min ischemic exercise, 15-min reperfusion). Results: Ischaemia/reperfusion caused a significant decline in FMD (continuous training (n = 10): 5.2 ± 2.5 to 3.4 ± 1.6%, high-intensity interval training (n = 10): 5.3 ± 2.6 to 3.5 ± 1.6%, P = 0.01), which was not different between groups (P > 0.05). Training improved maximal workload and fitness (P < 0.05), with no differences between groups (P > 0.05). Exercise training did not alter FMD (P > 0.05), whilst ischaemia/reperfusion did not impair FMD after exercise training (continuous training: 4.8 ± 3.0 to 4.2 ± 2.3%, high-intensity interval training: 4.7 ± 2.5 to 3.8 ± 2.3%, P > 0.05). No changes were found in FMD before or after ischaemia/reperfusion after 12-weeks in controls (n = 9). Conclusion: We found that 12-week exercise training in heart failure patients mitigated endothelial ischaemia-reperfusion injury, an effect independent of the type of exercise. These changes may contribute to the cardioprotective effects of exercise training, whilst our findings highlight the potency of exercise as a preconditioning stimulus.

Management of Gait Impairments in Chronic Unilateral Upper Motor Neuron Lesions: A Review.

Importance: Gait impairments are common in patients with chronic supratentorial upper motor neuron lesions and are a source of disability. Clinical management aimed at improving the gait pattern in these patients is generally perceived as a challenging task because many possible abnormalities may interact. Moreover, a multitude of treatment options exist, ranging from assistive devices and muscle stretching to pharmacologic and surgical interventions, but evidence is inconclusive for most approaches and clear treatment guidelines are lacking. Observations: Gait deviations in adults with a chronic supratentorial upper motor neuron lesion can approximately be reduced to the following 3 groups of primary deficits: (1) imbalance of muscle strength, length, and activity around the ankle and tarsal joints leading to pes equinovarus or pes equinus; (2) calf muscle weakness; and (3) overactivity of proximal leg muscles. Conclusions and Relevance: A stepwise treatment algorithm emphasizes medical-technical interventions, which are based on evidence when available and otherwise reflect practice-based experience.

Impact of prolonged walking exercise on cardiac structure and function in cardiac patients versus healthy controls.

BACKGROUND AND DESIGN: Previous studies have demonstrated that endurance exercise can cause an acute transient decrease in cardiac function in healthy subjects. Whether this also occurs in cardiac patients is unknown. We investigated the impact of prolonged single day and three-day walking exercise on cardiac function and cardiac biomarkers between cardiac patients and healthy controls in an observational study. METHODS: We recruited 10 cardiac patients (nine males, one female, 68 ± 5 years) and 10 age- and sex-matched healthy control subjects (nine males, one female, 68 ± 4 years) to perform 30 or 40 km of walking exercise per day for three consecutive days. Cardiac function was examined using echocardiography and cardiac biomarkers (cardiac troponin and B-type natriuretic peptide) with blood samples. Data were collected before walking and directly after walking on day 1 and day 3. RESULTS: Post-exercise early systolic tissue contraction velocity of the left ventricle (p = 0.005) and global longitudinal left ventricle strain (P = 0.026) were increased in both groups compared with baseline. Post-exercise right ventricle peak early diastolic tissue filling velocity and systolic blood pressure/left ventricle end-systolic volume ratio decreased in both groups (p = 0.043 and p = 0.028, respectively). Post-exercise cardiac troponin levels increased (p = 0.045) but did not differ across groups (p = 0.60), whereas B-type natriuretic peptide levels did not change (p = 0.43). CONCLUSION: This study suggests that stable cardiac patients are capable of performing three days of prolonged walking exercise without clinically significant acute overall deterioration in cardiac function or more pronounced increase in cardiac biomarkers compared with healthy controls.

Heart failure is associated with exaggerated endothelial ischaemia-reperfusion injury and attenuated effect of ischaemic preconditioning.

BACKGROUND: Reperfusion is mandatory after ischaemia, but it also triggers ischaemia-reperfusion (IR)-injury. It is currently unknown whether heart failure alters the magnitude of IR-injury. Ischaemic preconditioning can limit IR-injury. Since ischaemic preconditioning is typically applied in subjects at risk for cardiovascular complications, it is of clinical importance to understand its efficacy in heart failure patients. OBJECTIVE: To examine the magnitude of endothelial IR-injury, and the ability of ischaemic preconditioning to protect against endothelial IR-injury in heart failure. METHODS: We included 15 subjects with heart failure (67 ± 10 years, New York Heart Association class II/III) and 15 healthy, age- and sex-matched controls (65 ± 9 years). We examined brachial artery endothelial function using flow-mediated dilation before and after arm IR (induced by 5-min ischaemic handgrip exercise +15 min reperfusion). IR was preceded by ischaemic preconditioning (consisting in three cycles of 5-min upper arm cuff inflation to 220 mmHg) or no inflation. RESULTS: A significant interaction-effect was found for the change in flow-mediated dilation after IR between groups (two-way ANOVA interaction-effect: p = 0.01). Whilst post-hoc analysis revealed a significantly decline in flow-mediated dilation in both groups (p < 0.05), the decline in flow-mediated dilation in heart failure patients (6.2 ± 3.6% to 3.3 ± 1.8%) was significantly larger than that observed in controls (4.9 ± 2.1 to 4.1 ± 2.0). Neither in heart failure patients nor controls was the decrease in flow-mediated dilation after IR altered by ischaemic preconditioning (three-way ANOVA interaction: p = 0.87). CONCLUSION: We found that patients with heart failure are associated with exaggerated endothelial IR-injury compared with age- and sex-matched, healthy controls, which may contribute to the poor clinical prognosis in heart failure. Furthermore, we found no protective effect of ischaemic preconditioning (3 × 5-min forearm ischaemia) against endothelial IR-injury in heart failure patients.

Altered core and skin temperature responses to endurance exercise in heart failure patients and healthy controls.

BACKGROUND: Exercise training represents a central aspect of rehabilitation of heart failure patients. Previous work on passive heating suggests impaired thermoregulatory responses in heart failure patients. However, no previous study directly examined thermoregulatory responses to an exercise bout, that is, active heating, as typically applied in rehabilitation settings in heart failure. DESIGN: Cross-sectional observational study to compare changes in core body temperature (Tcore) and skin temperature (Tskin) during exercise between heart failure patients and controls. METHODS: Fourteen heart failure subjects (65 ± 7 years, 13:1 male:female) and 14 healthy controls (61 ± 5 years, 12:2 male:female) were included. Tcore (telemetric temperature pill) and Tskin (skin thermistors) were measured continuously during a 45-min cycle exercise at comparable relative exercise intensity. RESULTS: Tcore increased to a similar extent in both groups (controls 1.1 ± 0.4℃, heart failure patients 0.9 ± 0.3℃, 'time*group': p = 0.15). Tskin decreased during the initial phase of exercise in both groups, followed by an increase in Tskin in controls (1.2 ± 1.0℃), whilst Tskin remained low in HF patients (-0.3 ± 1.4℃) ('time*group': p < 0.001). Furthermore, we found that a given change in Tcore was associated with a smaller increase in Tskin in heart failure patients compared with controls. When comparing heart failure patients and controls who performed exercise at similar absolute workload, between-group differences disappeared (p-values > 0.05). CONCLUSION: Heart failure patients and controls show comparable exercise-induced increase in Tcore, whilst heart failure patients demonstrate altered Tskin responses to exercise and attenuated elevation in Tskin per increase in Tcore. These impaired thermoregulatory responses to exercise are, at least partly, explained by the lower absolute workload and lower physical fitness level in heart failure patients.

Effects of High-Intensity Interval Training versus Continuous Training on Physical Fitness, Cardiovascular Function and Quality of Life in Heart Failure Patients.

INTRODUCTION: Physical fitness is an important prognostic factor in heart failure (HF). To improve fitness, different types of exercise have been explored, with recent focus on high-intensity interval training (HIT). We comprehensively compared effects of HIT versus continuous training (CT) in HF patients NYHA II-III on physical fitness, cardiovascular function and structure, and quality of life, and hypothesize that HIT leads to superior improvements compared to CT. METHODS: Twenty HF patients (male:female 19:1, 64±8 yrs, ejection fraction 38±6%) were allocated to 12-weeks of HIT (10*1-minute at 90% maximal workload-alternated by 2.5 minutes at 30% maximal workload) or CT (30 minutes at 60-75% of maximal workload). Before and after intervention, we examined physical fitness (incremental cycling test), cardiac function and structure (echocardiography), vascular function and structure (ultrasound) and quality of life (SF-36, Minnesota living with HF questionnaire (MLHFQ)). RESULTS: Training improved maximal workload, peak oxygen uptake (VO2peak) related to the predicted VO2peak, oxygen uptake at the anaerobic threshold, and maximal oxygen pulse (all P<0.05), whilst no differences were present between HIT and CT (N.S.). We found no major changes in resting cardiovascular function and structure. SF-36 physical function score improved after training (P<0.05), whilst SF-36 total score and MLHFQ did not change after training (N.S.). CONCLUSION: Training induced significant improvements in parameters of physical fitness, although no evidence for superiority of HIT over CT was demonstrated. No major effect of training was found on cardiovascular structure and function or quality of life in HF patients NYHA II-III. TRIAL REGISTRATION: Nederlands Trial Register NTR3671.

Heart failure patients demonstrate impaired changes in brachial artery blood flow and shear rate pattern during moderate-intensity cycle exercise.

NEW FINDINGS: What is the central question of this study? We explored whether heart failure (HF) patients demonstrate different exercise-induced brachial artery shear rate patterns compared with control subjects. What is the main finding and its importance? Moderate-intensity cycle exercise in HF patients is associated with an attenuated increase in brachial artery anterograde and mean shear rate and skin temperature. Differences between HF patients and control subjects cannot be explained fully by differences in workload. HF patients demonstrate a less favourable shear rate pattern during cycle exercise compared with control subjects. Repeated elevations in shear rate (SR) in conduit arteries, which occur during exercise, represent a key stimulus to improve vascular function. We explored whether heart failure (HF) patients demonstrate distinct changes in SR in response to moderate-intensity cycle exercise compared with healthy control subjects. We examined brachial artery SR during 40 min of cycle exercise at a work rate equivalent to 65% peak oxygen uptake in 14 HF patients (65 ± 7 years old, 13 men and one woman) and 14 control subjects (61 ± 5 years old, 12 men and two women). Brachial artery diameter, SR and oscillatory shear index (OSI) were assessed using ultrasound at baseline and during exercise. The HF patients demonstrated an attenuated increase in mean and anterograde brachial artery SR during exercise compared with control subjects (time × group interaction, P = 0.003 and P < 0.001, respectively). Retrograde SR increased at the onset of exercise and remained increased throughout the exercise period in both groups (time × group interaction, P = 0.11). In control subjects, the immediate increase in OSI during exercise (time, P < 0.001) was normalized after 35 min of cycling. In contrast, the increase in OSI after the onset of exercise did not normalize in HF patients (time × group interaction, P = 0.029). Subgroup analysis of five HF patients and five control subjects with comparable workload (97 ± 13 versus 90 ± 22 W, P = 0.59) confirmed the presence of distinct changes in mean SR during exercise (time × group interaction, P = 0.030). Between-group differences in anterograde/retrograde SR or OSI did not reach statistical significance (time × group interactions, P > 0.05). In conclusion, HF patients demonstrate a less favourable SR pattern during cycle exercise than control subjects, characterized by an attenuated mean and anterograde SR and by increased OSI.

Acute change in vascular tone alters intima-media thickness.

Atherosclerosis is a lifelong process involving artery wall thickening. Increased wall thickness has been widely adopted as a preclinical surrogate marker of atherosclerosis. A prerequisite for such a surrogate marker is that it is a structural characteristic of the vessel wall that is not subject to acute changes. The purpose of this study was to examine the acute effects of vasodilator drug administration on wall thickness of the carotid and superficial femoral arteries. High-resolution ultrasound was used to examine carotid and femoral artery diameters and wall thickness in 15 young (25±4 years of age) and 15 older (70±6 years of age) healthy men who were administered sublingual glyceryl trinitrate. Diameter and wall thickness were collected before and across a 10-minute period after glyceryl trinitrate administration. Glyceryl trinitrate induced a significant increase in carotid and femoral artery diameter and a decrease in wall thickness in both young and older men (both P<0.001). The latter was significantly larger than in young men (both P<0.01). The changes in carotid artery wall thickness in both young (35±23 µm) and older men (71±46 µm) approximate those considered prognostically relevant. Collectively, our data suggest that vasodilator drug administration induces a rapid and marked decrease in wall thickness, which mirrors conduit artery vasodilation in both young and older men. This finding confirms the presence of acute changes in wall thickness and has important implications for future studies that assess artery wall characteristics as a surrogate measure of atherosclerosis.