Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO_2max), cardio-metabolic risk and psychological health which are comparable to MICT. Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m^-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15–60 seconds, >90% HR_max) interspersed with periods of recovery cycling (≤25 min.session^-1, 3 sessions.week^-1). MICT participants performed continuous cycling (~70% HR_max, 30–45 min.session^-1, 5 sessions.week^-1). VO_2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO_2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.

Objective.: Corrected QT (QTc) interval predicts all-cause and cardiovascular mortality and may contribute to the increased mortality risk in rheumatoid arthritis (RA). Animal experiments have shown that proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin 1 (IL-1)] can prolong cardiomyocyte action potential. We sought to determine whether elevations in circulating inflammatory cytokines were independently associated with QTc prolongation in patients with RA.Methods.: One hundred twelve patients [median age 62 (interquartile range 17) yrs; 80 women (71%)] from a well-characterized RA cohort underwent baseline 12-lead electrocardiograms for QT interval measurement and contemporary blood sampling to assess concentrations of inflammatory markers including C-reactive protein (CRP), TNF-α, and interleukins (IL-1α, IL-1β, IL-6, IL-10). QTc was calculated using the Bazett (QT_BAZ= QT ÷ √RR) and Framingham Heart Study (QT_FHS= QT + 0.154 × [1 – RR]) heart rate correction formulas.Results.: Inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10) were positively correlated with QT_BAZ(Spearman rank correlation coefficient rho = 0.199, 0.210, 0.222, 0.333; all p < 0.05). In multivariable regression analysis, these associations were all confounded by age except IL-10, where higher tertile groups were independently and positively associated with QT_BAZ(β = 0.202, p = 0.023) and QT_FHS(β = 0.223, p = 0.009) when compared to the lower tertile. CRP (per unit increase) was independently associated with QT_BAZ(β = 0.278, p = 0.001), but not QT_FHS.Conclusion.: To our knowledge, ours is the first study demonstrating a contemporary link between inflammatory cytokines and QT interval in humans. Our results suggest that a lower inflammatory burden may protect against QTc prolongation in patients with RA. However, further studies are required to confirm the effects of pro- and antiinflammatory cytokines on QTc interval.

Key points: Heart rate increases during exercise due to withdrawal of cardiac parasympathetic tone and increased cardiac sympathetic nerve activity. We investigated the autonomic mechanisms whereby heart rate is regulated by the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex). Heart rate responses elicited by partial flow restriction during leg cycling (enhanced metaboreflex activation) and post‐exercise muscle ischemia following leg cycling and handgrip (isolated metaboreflex activation) were evaluated under control (no drug), β‐adrenergic blockade and parasympathetic blockade conditions. We show that the muscle metaboreflex principally elevates heart rate by increasing cardiac sympathetic activity, and only following dynamic exercise with a large muscle mass (post‐exercise muscle ischemia following leg cycling) does the partial withdrawal of cardiac parasympathetic tone make a contribution to this heart rate response. These findings may have implications for patient populations in which alterations in skeletal muscle afferent sensitivity have been identified. Abstract  We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi‐lateral thigh cuff inflation) during leg cycling exercise, (2) isolated muscle metaboreflex activation (post‐exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), β₁‐adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR increased with partial flow restriction during leg cycling in the control condition (Δ11 ± 2 beats min⁻¹; P < 0.05). The magnitude of this increase in HR was similar with parasympathetic blockade (Δ11 ± 2 beats min⁻¹), but attenuated with β‐adrenergic blockade (Δ4 ± 1 beats min⁻¹; P < 0.05 vs. control and parasympathetic blockade). During PEI following leg cycling exercise, HR remained similarly elevated above rest under all conditions (Δ11 ± 2, Δ13 ± 3 and Δ9 ± 4 beats min⁻¹, for control, β‐adrenergic and parasympathetic blockade; P > 0.05 between conditions). During PEI following handgrip, HR was similarly elevated from rest under control and parasympathetic blockade (Δ4 ± 1 vs. Δ4 ± 2 beats min⁻¹; P > 0.05 between conditions) conditions, but attenuated with β‐adrenergic blockade (Δ0.2 ± 1 beats min⁻¹; P > 0.05 vs. rest). Thus muscle metaboreflex activation‐mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg cycling) is there a contribution from the partial withdrawal of cardiac parasympathetic tone.

Key points: Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of cardiovascular mortality. Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity heighten cardiovascular risk, althogh whether such autonomic dysfunction is present in RA is not known. In the present study, we observed an increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in patients with RA compared to matched controls. Pain was positively correlated with sympathetic nerve activity and negatively correlated with cardiac baroreflex sensitivity. The pattern of autonomic dysfunction that we describe may help to explain the increased cardiovascular risk in RA, and raises the possibility that optimizing pain management may resolve autonomic dysfunction in RA. Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesized that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age‐ and sex‐matched RA‐normotensive (n = 13), RA‐hypertensive patients (RA‐HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C‐reactive protein (hs‐CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA‐HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts min^–1) compared to NC (22 ± 9 bursts min^–1; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), whereas cardiac BRS (cBRS) was reduced in RA, RA‐HTN and HTN patients [5(3–8), 4 (2–7), 6 (4–9) ms mmHg^–1] compared to NC [11 (8–15) ms mmHg^–1; P = 0.002]. HR was independently associated with hs‐CRP. Increased MSNA and reduced cBRS were associated with hs‐CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events.

Neutrophils and monocytes are key components of the innate immune system that undergo age‐associated declines in function. This study compared the impact of high‐intensity interval training (HIIT) and moderate‐intensity continuous training (MICT) on immune function in sedentary adults. Twenty‐seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO_2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO_2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune‐enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.