Tetrahydrobiopterin Administration Augments Exercise-Induced Hyperemia and Endothelial Function in Patients With Systemic Sclerosis

Systemic sclerosis (SSc) is a rare, auto-immune disease with variably progressive fibrosis of the skin and internal organs, as well as vascular dysfunction. Recently, we demonstrated a decrement in exercising skeletal muscle blood flow and endothelium-dependent vasodilation in SSc, but the mechanisms responsible for these impairments have not been investigated. Thus, we sought to determine if acute administration of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase (eNOS), would improve hyperemia and brachial artery vasodilation during progressive handgrip exercise in SSc. Thirteen patients with SSc (63 ± 11 years) participated in this placebo-controlled, randomized, double-blind, crossover study. Tetrahydrobiopterin (10 mg/kg) administration resulted in a ~4-fold increase in circulating BH4 concentrations (P < 0.05). Cardiovascular variables at rest were unaffected by BH4 (P > 0.05). During handgrip exercise, BH4 administration increased brachial artery blood flow (placebo: 200 ± 87; BH4: 261 ± 115 ml/min; P < 0.05) and vascular conductance (placebo: 2.0 ± 0.8; BH4: 2.5 ± 1.0 ml/min/mmHg; P < 0.05), indicating augmented resistance artery vasodilation. Tetrahydrobiopterin administration also increased brachial artery vasodilation in response to exercise (placebo: 12 ± 6; BH4: 17 ± 7%; P < 0.05), resulting in a significant upward shift in the slope relationship between Δ brachial artery vasodilation and Δ shear rate (placebo: 0.030 ± 0.007; BH4: 0.047 ± 0.007; P < 0.05) that indicates augmented sensitivity of the brachial artery to vasodilate to the sustained elevations in shear rate during handgrip exercise. These results demonstrate the efficacy of acute BH4 administration to improve both resistance and conduit vessel endothelial function in SSc, suggesting that eNOS recoupling may be an effective strategy for improving vasodilatory capacity in this patient group.

Inflammatory Cytokines Response to Isometric Handgrip Exercise and the Effects of Duration and Intensity of the Isometric Effort in Prehypertensive Subjects

BACKGROUND Chronic low grade systemic inflammation has been identified as a major risk factor for chronic diseases. The potential for physical exercise to induce anti-inflammatory effect is now increasingly being explored but there is paucity of data regarding the effects isometric exercise on inflammatory cytokines. The objective of this study was to investigate the responses of selected inflammatory cytokines to isometric handgrip exercise and identify possible effects of intensity and duration of the isometric effort on these variables. CASE PRESENTATION: A total of one hundred and ninety two (N=192) sedentary pre-hypertensive subjects, aged between 30-50years were recruited into the study and randomly distributed into three groups of 64 subjects each. The subjects performed a 24 consecutive day’s isometric hand grip exercise at 30% Maximum Voluntary Contraction. At the end of the 24 days, the group one (GP1) discontinued with the exercise protocol while the group two (GP2) continued the exercise protocol for another 24 consecutive days and the group three (GP3) continued with the exercise protocol for another 24 consecutive days but at 50%MVC. The parameters used to assess for the inflammatory cytokine variables included interleukin 10, interleukin 6 and tumor necrotic factor. At the end of the study, there was an increase in the resting values of interleukin 10 across the three groups while the resting values of interleukin 6 and tumor necrotic factor reduced significantly across groups. CONCLUSIONS: The reductions noted in the pro-inflammatory cytokines and increase in the anti-inflammatory cytokines could have a positive impact in the management of chronic diseases. It was also found that increase in intensity and/or duration produced more proportionate effect.

Penerapan Isometric Handgrip Exercisedan Slow Deep Breathing Exercise Untuk Menurunkan Tekanan Darah

Hypertension is an increase in blood pressure with systolic above 140 mmHg and diastolic above 90 mmHg. One of the non-pharmacological methods to lower blood pressure is to do isometric handgrip exercise and slow deep breathing exercise. The purpose of this case study is to evaluate blood pressure by implementing isometric handgrip exercise and slow deep breathing exercise toward hypertensive patients within five day of training (twice per day). There were two hipertensive patients involvid in this study. The results of this case study showed that the blood pressure of both patients dropped to normal. The firt patients blood pressure dropped to normal from 160/100 mmHg to 130/80 mmHg after the intervention. Similarly, the second patients blood pressure reduced from 170/100 mmHg to 120/80 mmHg. This study conclusion that the isometric handgrip exercise and slow deep breathing exercise can lower blood pressure.Keywords: Hypertension; Isometric Handgrip; Slow Deep Breathing AbstrakHipertensi adalah peningkatan tekanan darah dengan sistolik diatas 140 mmHg dan diastolik diatas 90 mmHg.salah satu tindakan nonfarmakologi yang dapat menurunkan tekanan darah adalah dengan melakukan latihan isometric handgrip exercise dan slow deep breathing exercise. Tujuan dilakukannya penerapan studi kasus ini adalah untuk menurunkan tekanan darah dengan menggunakan latihan isometric handgrip exercise dan slow deep breathing exercise pada keluarga dengan hipertensi. Metode yang digunakan adalah dengan penerapan latihan isometric handgrip exercise dan slow deep breathing exercise. Hasil dari studi kasus ini menunjukkan adanya penurunan tekanan darah pada klien I dan II yang disertai dengan penurunan rasa nyeri, klien I dengan tekanan darah 160/100 mmHg turun menjadi 130/80 mmHg dan klien II dengan tekanan darah 170/100 mmHg turun menjadi 120/80 mmHg. Kesimpulan dari penerapan isometric handgrip exercise dan slow deep breathing exercise adalah bahwa penerapan latihan isometric handgrip exercise dan slow deep breathing exercise dapat menurunkan tekanan darah selama 5 hari latihan dengan 2 kali pertemuan setiap harinya.Kata kunci: Hipertensi; Isometric Handgrip; Slow Deep Breathing

Dynamic Handgrip Exercise: Feasibility and Physiologic Stress Response of a Potential Needle-Free Cardiac Magnetic Resonance Stress Test

Background: Cardiac magnetic resonance (CMR) pharmacological stress-testing is a well-established technique for detecting myocardial ischemia. Although stressors and contrast agents seem relatively safe, contraindications and side effects must be considered. Substantial costs are further limiting its applicability. Dynamic handgrip exercise (DHE) may have the potential to address these shortcomings as a physiological stressor. We therefore evaluated the feasibility and physiologic stress response of DHE in relation to pharmacological dobutamine-stimulation within the context of CMR examinations.Methods: Two groups were prospectively enrolled: (I) volunteers without relevant disease and (II) patients with known CAD referred for stress-testing. A both-handed, metronome-guided DHE was performed over 2 min continuously with 80 contractions/minute by all participants, whereas dobutamine stress-testing was only performed in group (II). Short axis strain by fast-Strain-ENCoded imaging was acquired at rest, immediately after DHE and during dobutamine infusion.Results: Eighty middle-aged individuals (age 56 ± 17 years, 48 men) were enrolled. DHE triggered significant positive chronotropic (HRrest: 68 ± 10 bpm, HRDHE: 91 ± 13 bpm, p < 0.001) and inotropic stress response (GLSrest: −19.4 ± 1.9%, GLSDHE: −20.6 ± 2.1%, p < 0.001). Exercise-induced increase of longitudinal strain was present in healthy volunteers and patients with CAD to the same extent, but in general more pronounced in the midventricular and apical layers (p < 0.01). DHE was aborted by a minor portion (7%) due to peripheral fatigue. The inotropic effect of DHE appears to be non-inferior to intermediate dobutamine-stimulation (GLSDHE= −19.5 ± 2.3%, GLSDob= −19.1 ± 3.1%, p = n.s.), whereas its chronotropic effect was superior (HRDHE= 89 ± 14 bpm, HRDob= 78 ± 15 bpm, p < 0.001).Conclusions: DHE causes positive ino- and chronotropic effects superior to intermediate dobutamine-stimulation, suggesting a relevant increase of myocardial oxygen demand. DHE appears to be safe and timesaving with broad applicability. The data encourages further studies to determine its potential to detect obstructive CAD.

The effect of extracellular hyperosmolality on sweat rate during metaboreflex activation in passively heated young men

Metaboreflex activation augments sweating during mild-to-moderate hyperthermia in euhydrated (isosmotic isovolemic) individuals. Recent work indicates that extracellular hyperosmolality may augment metaboreflex-mediated elevations in sympathetic nervous activity. Our primary objective was therefore to test the hypothesis that extracellular hyperosmolality would exacerbate metaboreflex-mediated increases in sweat rate. On two separate occasions, 12 young men (mean (SD): 25 (5) years) received a 90-min intravenous infusion of either 0.9% saline (isosmotic condition, ISO) or 3.0% saline (hyperosmotic condition, HYP), resulting in a post-infusion serum osmolality of 290 (3) and 301 (7) mOsm/kg, respectively. A whole-body water perfusion suit was then used to increase esophageal temperature by 0.8°C above resting. Participants then performed a metaboreflex activation protocol consisting of 90 s isometric handgrip exercise (40% of their pre-determined maximum voluntary contraction), followed by 150 s of brachial occlusion (trapping produced metabolites within the limb). Metaboreflex-induced sweating was quantified as the change in global sweat rate (from pre-isometric handgrip exercise to brachial occlusion), estimated as the surface area-weighted average of local sweat rate on the abdomen, axilla, chest, bicep, quadriceps, and calf, measured using ventilated capsules (3.8 cm2). We also explored whether this response differed between body regions. The change in global sweat rate due to metaboreflex activation was significantly greater in HYP compared to ISO (0.03 mg/min/cm2 [95% confidence interval: 0.00, 0.06]; p=0.047), but was not modulated by body region (site*condition interaction: p=0.679). These findings indicate that extracellular hyperosmolality augments metaboreflex-induced increases in global sweat rate, with no evidence for region-specific differences.

The Impact of Cognitive and Physical Effort Exertion on Physical Effort Decisions: A Pilot Experiment

Research suggests that cognitive fatigue has a negative impact on physical activity participation. However, the mechanisms underlying this effect are yet unclear. Using an effort-based decision-making paradigm, we examined whether individuals weigh physical effort-costs more strongly when they are cognitively or physically fatigued. Twenty university students visited the lab on three occasions. On each visit, participants underwent a manipulation that was designed to either induce cognitive fatigue (i.e., 2-back task), physical fatigue (i.e., handgrip exercise), or served as a control condition (i.e., documentary watching). After the manipulations, participants performed an effort-based decision-making task in which they decided for 125 offers whether they accepted the offer to exert the required level of physical effort to obtain rewards that varied in value. The probability to accept offers declined with increasing effort requirements whereas the general probability to accept offers was not reduced by any of the experimental conditions. As expected, the decline in accepted offers with increasing effort requirements was stronger after prolonged exertion of physical effort compared to the control condition. Unexpectedly, this effect was not found after exerting cognitive effort, and exploratory analyses revealed that the impact of physical effort exertion on physical effort-based decisions was stronger than that of cognitive effort exertion. These findings suggest that people weight future physical effort-costs more strongly after exerting physical effort, whereas we could not find any evidence for this after exerting cognitive effort. We discuss multiple explanations for this discrepancy, and outline possibilities for future research.