Reid A. Mitchell

Sex differences in respiratory responses to ventilatory stress may contribute to exercise tolerance and dyspnoea perception, with potential implications across health and respiratory disease. We hypothesized that dead space loading (DSL) normalized to 15% of forced vital capacity would increase exertional dyspnoea, exacerbate inherent sex‐based differences in the respiratory system's response to exercise, and elicit higher diaphragmatic and extra‐diaphragmatic respiratory muscle activity in females than in males. Forty healthy, non‐smokers (20 males, 20 females; 24 ± 5 years old; maximal O ₂ uptake: 96 ± 20% predicted) completed familiarization followed by two maximal incremental cycling tests on separate days with and without DSL in a randomized, single‐blinded and counter‐balanced order. Diaphragm activity was recorded using a multi‐pair electrode oesophageal catheter, while extra‐diaphragmatic inspiratory muscle activity was recorded with bipolar surface electrodes. DSL was 797 ± 114 mL in males and 585 ± 71 mL in females ( P  < 0.001). Dyspnoea ratings increased similarly in both sexes with DSL, with no sex differences during or after exercise. Minute ventilation was increased with DSL throughout exercise [peak‐males: Δ16 L·min ⁻¹ ·%peak work ⁻¹ , CI: (12,19), P  < 0.001; females: Δ11 L·min ⁻¹ ·%peak work ⁻¹ , CI: (8,15), P  < 0.001], as well as indices of mechanical ventilatory constraints (e.g. tidal volume, power of breathing) at peak exercise in both sexes, where males had a greater increase with DSL for most variables than females. Diaphragm and extra‐diaphragmatic activity were increased with DSL in both sexes, with a greater increase in extra‐diaphragmatic activity in females near maximal exercise. These findings suggest that while sex differences in respiratory function and respiratory muscle activation exist, they do not necessarily translate to sex differences in dyspnoea perception during maximal incremental cycling. image Key points: Sex differences in respiratory anatomy and function are known to influence dyspnoea perception during exercise; however, the effects of higher ventilatory demand and mechanical ventilatory constraints on these differences remain poorly understood. Using a simple‐randomization, single‐blinded and counter‐balanced study design, we stimulated minute ventilation () and increased mechanical ventilatory constraints during maximal incremental cycling using dead space loading (DSL) customized to 15% of each individual's forced vital capacity. Dyspnoea was assessed using a multidimensional approach during and immediately after exercise. Despite increases in the sensations of breathing work/effort, unsatisfied inspiration and unsatisfied expiration with DSL in both sexes, there were no sex differences in dyspnoea perception during exercise with DSL. DSL increased and indicators of mechanical ventilatory constraints in both sexes compared to control exercise. Both sexes experienced an increase in diaphragmatic and extra‐diaphragmatic muscle activity, where females had a greater increase in extra‐diaphragmatic activity with DSL than males.

Key points: Diaphragm fatigue may increase the intensity (sensory dimension) and unpleasantness (affective dimension) of dyspnoea, which may partially explain why diaphragm fatigue negatively affects exercise performance. We hypothesized that diaphragm fatigue would negatively affect exercise performance via increases in both the intensity and unpleasantness of dyspnoea, and that the increase in dyspnoea would be mechanistically linked to an increase in diaphragmatic EMG (EMG_di), a surrogate measure of neural respiratory drive. Fatiguing the diaphragm prior to exercise reduced cycling performance and increased both the intensity and unpleasantness of dyspnoea. The change in submaximal dyspnoea unpleasantness was significantly correlated with the change in cycling performance. Pre‐fatigue of the diaphragm did not increase EMG_di during exercise and is therefore unrelated to the increase in either the sensory or affective dimension of exertional dyspnoea. The purpose of this study was to examine the effect of diaphragm fatigue on the multidimensional components of dyspnoea and diaphragm electromyography (EMG_di) during cycling. Sixteen healthy males (age = 27 ± 5 yr, = 45.8 ± 9.8 ml kg⁻¹ min⁻¹) completed two high‐intensity, time‐to‐exhaustion cycling tests in randomized order: (i) inspiratory pressure threshold loading (PTL) prior to exercise to induce diaphragm fatigue (pre‐DF) and (ii) no PTL (control). Diaphragm fatigue after PTL was confirmed via cervical magnetic stimulation of the phrenic nerves. Dyspnoea intensity and unpleasantness were measured throughout exercise with the 0–10 category‐ratio Borg scale and following exercise using the Multidimensional Dyspnoea Profile (MDP). EMG_di was continuously recorded via a multipair oesophageal electrode catheter. Time‐to‐exhaustion decreased with pre‐DF vs. control (9.0 ± 5.5 vs. 10.7 ± 7.5 min, P = 0.023). Pre‐DF increased dyspnoea intensity ratings by 0.6 ± 1.0 Borg 0–10 units at the highest equivalent submaximal exercise time (HESET) a participant could achieve in both conditions (P = 0.020). Dyspnoea unpleasantness ratings increased with pre‐DF by 0.5 ± 1.0, 0.7 ± 1.2 and 0.9 ± 1.4 (all P < 0.05) Borg 0–10 units during the 2nd, 3rd and 4th minutes of exercise, respectively. There was a significant correlation between the change in breathing unpleasantness ratings at HESET and the change in time‐to‐exhaustion (r = 0.66, P = 0.006). The immediate perception domain, a combination of peak unpleasantness and specific dyspnoea descriptor intensity ratings, was the only component of the MDP that was significantly increased with pre‐DF (4.3 ± 1.9 vs. 3.6 ± 1.8, P = 0.04). There were no significant differences in EMG_di. In conclusion, diaphragm fatigue has negative effects on multiple domains of dyspnoea, which may partially explain why exercise performance decreases with it.

Purpose Aerobars place a cyclist in a position where the trunk is flexed forward and the elbows are close to the midline of the body. This position is known to improve cycling aerodynamics and time trial race performance compared with upright cycling positions. However, the aggressive nature of this position may have important cardiorespiratory and metabolic consequences. The purpose of this investigation was to examine the respiratory mechanical, ventilatory, metabolic, and sensory consequences of cycling while using aerobars during laboratory-based cycling. Methods Eleven endurance-trained male cyclists (age, 26 ± 9 yr; V˙O2peak, 55 ± 5 mL·kg−1·min−1) were recruited. Visit 1 consisted of an incremental cycling test to determine peak power output. Visit 2 consisted of 6-min bouts of constant load cycling at 70% of peak incremental power output in the aerobar position, drop position, and upright position while grasping the brake hoods. Metabolic and ventilatory responses were measured using a commercially available metabolic cart, and respiratory pressures were measured using an esophageal catheter. Results Cycling in the aerobar position significantly increased the work of breathing (Wb), power of breathing (Pb), minute ventilation, ventilatory equivalent for oxygen and carbon dioxide, and transdiaphragmatic pressure compared with the upright position. Increases in the Wb and Pb in the aerobars relative to the upright position were strongly correlated with the degree of thoracic restriction, measured as the shoulder-to-aerobar width ratio (Wb: r = 0.80, P = 0.01; Pb: r = 0.69, P = 0.04). Conclusions Aerobars significantly increase the mechanical cost of breathing and leads to greater ventilatory inefficiency compared with upright cycling. Future work is needed to optimize aerobar width to minimize the respiratory mechanical consequences while optimizing aerodynamics.

New Findings: What is the central question of this study? Does manipulation of the work of breathing during high‐intensity exercise alter respiratory and locomotor muscle blood flow? What is the main finding and its importance? We found that when the work of breathing was reduced during exercise, respiratory muscle blood flow decreased, while locomotor muscle blood flow increased. Conversely, when the work of breathing was increased, respiratory muscle blood flow increased, while locomotor muscle blood flow decreased. Our findings support the theory of a competitive relationship between locomotor and respiratory muscles during intense exercise. Manipulation of the work of breathing (WOB) during near‐maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to assess leg and respiratory muscle blood flow simultaneously during intense exercise while manipulating WOB. Our hypotheses were as follows: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow; and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 men, n = 3 women) performed a maximal cycle test (day 1) and a series of constant‐load exercise trials at 90% of peak work rate (day 2). On day 2, WOB was assessed with oesophageal balloon catheters and was increased (via resistors), decreased (via proportional assist ventilation) or unchanged (control) during the trials. Blood flow was assessed using near‐infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous Indocyanine Green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were significantly and inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the WOB increased locomotor blood flow. Oxygen uptake was not different during the control and resistor trials (3.8 ± 0.9 versus 3.7 ± 0.8 l min⁻¹, P > 0.05), but was lower on the proportional assist ventilator trial (3.4 ± 0.7 l min⁻¹, P < 0.05) compared with control. Our findings support the concept that respiratory muscle work significantly influences the distribution of blood flow to both respiratory and locomotor muscles.

Introduction Endovascular therapy is the standard of care for the treatment of proximal large vessel occlusion strokes (LVOS). Its safety and efficacy in the treatment of distal intracranial occlusions has not been well studied. Methods We retrospectively reviewed a prospectively collected endovascular database (September 2010-December 2015, n=898) for all patients with distal intracranial occlusions treated with endovascular therapy. Distal occlusions were defined as any occlusion of the anterior cerebral artery (ACA), any occlusion of the posterior cerebral artery (PCA), or any occlusion at or distal to the middle cerebral artery (MCA)-M3 opercular segment. Results Distal occlusions were treated in 70 patients. The mean age was 66+/-14% and 57% of the patients were male. Thirty-one (44%) of the patients received IV-tPA. The median pre-procedure NIHSS was 19 (IQR, 13–23). The distal occlusion was the primary treatment location in 54 patients and in 16 patients the distal occlusion was treated as a rescue strategy after successful treatment of a proximal LVOS. The locations of the primary cases were MCA-M3 (n=21), ACA with a concomitant MCA-M1 or MCA-M2 (n=16), ACA alone (n=9), PCA (n=6), and ACA with a concomitant MCA-M3 (n=2). The locations of the rescue cases were MCA-M3 (n=8), ACA (n=7), and both MCA-M3 and ACA (n=1). The most common treatment modalities employed were intra-arterial tPA (n=37, 52%), small (3 mm) stent-retrievers (n=24, 33%), and thromboaspiration (n=30, 42%). Near or complete reperfusion (mTICI 2b-3) was achieved in 56 cases (80%). Overall, there were 5 (7%) cases of any parenchymal hematoma (PH). However, two of the PHs were in patients with both a MCA-M1 and an ACA occlusion, and both of these hemorrhages were in the MCA territory. Thus only 3 PHs (4.3%) occurred in the territory of the treated distal occlusion with two of these patients also receiving IV tPA. At 90 days, 24 patients (40%) had a mRS of 0–2 and 13 (21%) had died. Conclusions Distal intracranial occlusions can be treated safely and successfully with endovascular therapy. Although promising our results need to be corroborated by larger prospective controlled studies. Disclosures J. Grossberg: None. L. Rebello: None. M. Bouslama: None. D. Haussen: None. M. Frankel: None. R. Nogueira: None.

The American Civil War caused upheaval and massive private bereavement, but the years 1861-1865 also defined a great nation. This book provides a concise introduction to events from the secession to the end of the war. It focuses on the military progress of the war Union and Confederate politics social change - particularly the emancipation of North American slaves The social history associated with the war is dealt with alongside the familiar military and political events. This inclusive approach allows the reader to consider equally the history of men and women, blacks and whites in the conflict. It deals with both the Union and the Confederacy, integrating the latest literature on the war and society into a clear account. The book concludes with an assessment of emancipation, the rebuilding of the economy, and the war's consequences. An array of primary documents supports the text, together with a chronology, glossary and Who's Who guide to key figures.