Acute inspiratory resistance training enhances endothelium-dependent dilation and retrograde shear rate in healthy young adults.

Inspiratory resistance training (IRT) yields significant reductions in resting blood pressure and improves vascular endothelial function. Our objective was to quantify the acute effects of IRT on brachial artery flow-mediated dilation (FMD) and shear rates (SRs) in healthy men and women. Twenty young adults (22.9 ± 3.4 years; 10 male, 10 female) completed a single bout of IRT or Rest condition in a randomized crossover design. Brachial artery FMD was performed before, 10 min after, and 40 min after the assigned condition. Brachial artery blood flow velocities were collected during IRT, separated by breathing cycle phase, and converted into SRs. FMD improved 10 min post-IRT (+1.86 ± 0.61%; p = 0.025) but returned to baseline by 40 min post-IRT (p = 0.002). Anterograde SR decreased by 10% and retrograde SR increased 102% during resisted inspiration, relative to baseline SR (p < 0.001). Anterograde SR increased by 7% in men and women (p < 0.001) and retrograde SR decreased by 12% in women but not men (p = 0.022) during unresisted expiration, relative to baseline SR. A single bout of IRT elicits a transient enhancement in FMD in both men and women. Acute IRT-related enhancements in SRs may contribute to sustained improvements in FMD that have been reported previously.

Time-Efficient, High-Resistance Inspiratory Muscle Strength Training Increases Exercise Tolerance in Midlife and Older Adults.

PURPOSE: This study aimed to determine if time-efficient, high-resistance inspiratory muscle strength training (IMST), comprising 30 inhalation-resisted breaths per day, improves cardiorespiratory fitness, exercise tolerance, physical function, and/or regional body composition in healthy midlife and older adults. METHODS: We performed a double-blind, randomized, sham-controlled clinical trial (NCT03266510) testing 6 wk of IMST (30 breaths per day, 6 d·wk -1 , 55%-75% maximal inspiratory pressure) versus low-resistance sham training (15% maximal inspiratory pressure) in healthy men and women 50-79 yr old. Subjects performed a graded treadmill exercise test to exhaustion, physical performance battery (e.g., handgrip strength, leg press), and body composition testing (dual x-ray absorptiometry) at baseline and after 6 wk of training. RESULTS: Thirty-five participants (17 women, 18 men) completed high-resistance IMST ( n = 17) or sham training ( n = 18). Cardiorespiratory fitness (V̇O 2peak ) was unchanged, but exercise tolerance, measured as treadmill exercise time during a graded exercise treadmill test, increased with IMST (baseline, 539 ± 42 s; end intervention, 606 ± 42 s; P = 0.01) but not sham training (baseline, 562 ± 39 s; end intervention, 553 ± 38 s; P = 0.69). IMST increased peak RER (baseline, 1.09 ± 0.02; end intervention, 1.13 ± 0.02; P = 0.012), peak ventilatory efficiency (baseline, 25.2 ± 0.8; end intervention, 24.6 ± 0.8; P = 0.036), and improved submaximal exercise economy (baseline, 23.5 ± 1.1 mL·kg -1 ⋅min -1 ; end intervention, 22.1 ± 1.1 mL·kg -1 ⋅min -1 ; P < 0.001); none of these factors were altered by sham training (all P > 0.05). Changes in plasma acylcarnitines (targeted metabolomics analysis) were consistently positively correlated with changes in exercise tolerance after IMST but not sham training. IMST was associated with regional increases in thorax lean mass (+4.4%, P = 0.06) and reductions in trunk fat mass (-4.8%, P = 0.04); however, peripheral muscle strength, muscle power, dexterity, and mobility were unchanged. CONCLUSIONS: These data suggest that high-resistance IMST is an effective, time-efficient lifestyle intervention for improving exercise tolerance in healthy midlife and older adults.

Time-efficient, high-resistance inspiratory muscle strength training increases cerebrovascular reactivity in midlife and older adults.

Aging is associated with increased risk for cognitive decline and dementia due in part to increases in systolic blood pressure (SBP) and cerebrovascular dysfunction. High-resistance inspiratory muscle strength training (IMST) is a time-efficient, intensive respiratory training protocol (30 resisted inspirations/day) that lowers SBP and improves peripheral vascular function in midlife/older adults with above-normal SBP. However, whether, and by what mechanisms, IMST can improve cerebrovascular function is unknown. We hypothesized that IMST would increase cerebrovascular reactivity to hypercapnia (CVR to CO2), which would coincide with changes to the plasma milieu that improve brain endothelial cell function and enhance cognitive performance (NIH Toolbox). We conducted a 6-wk double-blind, randomized, controlled clinical trial investigating high-resistance IMST [75% maximal inspiratory pressure (PImax); 6×/wk; 4 females, 5 males] vs. low-resistance sham training (15% PImax; 6×/wk; 2 females, 5 males) in midlife/older adults (age 50-79 yr) with initial above-normal SBP. Human brain endothelial cells (HBECs) were exposed to participant plasma and assessed for acetylcholine-stimulated nitric oxide (NO) production. CVR to CO2 increased after high-resistance IMST (pre: 1.38 ± 0.66 cm/s/mmHg; post: 2.31 ± 1.02 cm/s/mmHg, P = 0.020). Acetylcholine-stimulated NO production increased in HBECs exposed to plasma from after vs. before the IMST intervention [pre: 1.49 ± 0.33; post: 1.73 ± 0.35 arbitrary units (AU); P < 0.001]. Episodic memory increased modestly after the IMST intervention (pre: 95 ± 13; post: 103 ± 17 AU; P = 0.045). Cerebrovascular and cognitive function were unchanged in the sham control group. High-resistance IMST may be a promising strategy to improve cerebrovascular and cognitive function in midlife/older adults with above-normal SBP, a population at risk for future cognitive decline and dementia.NEW & NOTEWORTHY Midlife/older adults with above-normal blood pressure are at increased risk of developing cognitive decline and dementia. Our findings suggest that high-resistance inspiratory muscle strength training (IMST), a novel, time-efficient (5-10 min/day) form of physical training, may increase cerebrovascular reactivity to CO2 and episodic memory in midlife/older adults with initial above-normal blood pressure.

A short course of high-resistance, low-volume breathing exercise extends respiratory endurance and blunts cardiovascular responsiveness to constant load respiratory testing in healthy young adults.

Our objective was to evaluate the effects of 6-weeks high-resistance, low-volume inspiratory muscle strength training (IMST) on respiratory endurance, blood pressure (BP) and heart rate (HR) responsiveness to high respiratory workloads. Ten healthy young adults completed two constant-load resistive breathing tests to exhaustion (Tlim) (target pressure =65 % maximal inspiratory pressure [PImax]; duty cycle = 0.7; breathing frequency matched to eupnea) separated by 6-weeks high-resistance (75 % maximal inspiratory pressure, PImax), low-volume (30 inspiratory efforts/day, 5 days/week) IMST. Throughout resistive breathing trials we measured beat-to-beat changes in BP and HR, mouth pressure, inspiratory muscle work and perceived exertion. POST resistive breathing tests revealed significant gains in endurance (PRE: 362.0 ± 46.6 s vs. POST: 663.8 ± 110.3 s, p = 0.003) and increases in respiratory muscle work (PRE: -9445 ± 1562 mmHg.s vs. POST: -16648 ± 3761 mmHg.s, p = 0.069). Conversely, systolic and diastolic BP responses, HR and ratings of perceived exertion all declined. Consistent with previous observations, 6 weeks high resistance, low volume IMST lowered casual resting SBP (p = 0.002), DBP (p = 0.007) and mean arterial pressure (p = 0.001) and improved static inspiratory pressure. High resistance, low volume inspiratory muscle strength training extends respiratory endurance and attenuates BP responsiveness in healthy, recreationally-active young adults. The outcomes have implications for improved athletic performance and for attaining and/or maintaining cardiorespiratory fitness.

A multi-trial, retrospective analysis of the antihypertensive effects of high-resistance, low-volume inspiratory muscle strength training.

Above-normal blood pressure (BP) is a primary risk factor for cardiovascular diseases. In a retrospective analysis of five pilot trials, we assessed the BP-lowering effects of high-resistance inspiratory muscle strength training (IMST) in adults aged 18-82 years and the impact of IMST on maximal inspiratory pressure (PIMAX), a gauge of inspiratory muscle strength and independent disease risk factor. Participants were randomized to high-resistance IMST (75% PIMAX) or low-resistance sham (15% PIMAX) training (30 breaths/day, 5-7 days/wk, 6 wk). IMST (n = 67) reduced systolic BP (SBP) by 9 ± 6 mmHg (P < 0.01) and diastolic BP (DBP) by 4 ± 4 mmHg (P < 0.01). IMST-related reductions in SBP and DBP emerged by week 2 of training (-4 ± 8 mmHg and -3 ± 6 mmHg; P ≤ 0.01, respectively) and continued across the 6-wk intervention. SBP and DBP were unchanged with sham training (n = 61, all P > 0.05). Select subject characteristics slightly modified the impact of IMST on BP. Greater reductions in SBP were associated with older age (ß = -0.07 ± 0.03; P = 0.04) and greater reductions in DBP associated with medication-naïve BP (ß = -3 ± 1; P = 0.02) and higher initial DBP (ß = -0.12 ± 0.05; P = 0.04). PIMAX increased with high-resistance IMST and low-resistance sham training, with a greater increase from high-resistance IMST (+20 ± 17 vs. +6 ± 14 cmH2O; P < 0.01). Gains in PIMAX had a modest inverse relation with age (ß = -0.20 ± 0.09; P = 0.03) and baseline PIMAX (ß = -0.15 ± 0.07; P = 0.04) but not to reductions in SBP or DBP. These compiled findings from multiple independent trials provide the strongest evidence to date that high-resistance IMST evokes clinically significant reductions in SBP and DBP, and increases in PIMAX, in adult men and women.NEW & NOTEWORTHY In young-to-older adult men and women, 6 wk of high-resistance inspiratory muscle strength training lowers casual systolic and diastolic blood pressure by 9 mmHg and 4 mmHg, respectively, with initial reductions observed by week 2 of training. Given blood pressure outcomes with the intervention were only slightly altered by subject baseline characteristics (i.e., age, blood pressure medication, and health status), inspiratory muscle strength training is effective in lowering blood pressure in a broad range of adults.

Six Months of Inspiratory Muscle Training to Lower Blood Pressure and Improve Endothelial Function in Middle-Aged and Older Adults With Above-Normal Blood Pressure and Obstructive Sleep Apnea: Protocol for the CHART Clinical Trial.

Background: Cardiovascular disease is a major global health concern and prevalence is high in adults with obstructive sleep apnea (OSA). Lowering blood pressure (BP) can greatly reduce cardiovascular disease risk and physical activity is routinely prescribed to achieve this goal. Unfortunately, many adults with OSA suffer from fatigue, daytime sleepiness, and exercise intolerance-due to poor sleep quality and nocturnal hypoxemia-and have difficulty initiating and maintaining an exercise program. High-resistance inspiratory muscle strength training (IMST) is a simple, time-efficient breathing exercise consistently reported to reduce BP in small, selective groups of both healthy and at-risk adults. Herein we present the study protocol for a randomized clinical trial to determine the long-term efficacy of IMST performed regularly for 24 weeks in middle-aged and older adults with OSA. The primary outcome is casual systolic BP. Secondary outcomes are 24-h systolic BP and circulating plasma norepinephrine concentration. Other outcomes include vascular endothelial function (endothelial-dependent and -independent dilation), aortic stiffness, casual and 24-h diastolic BP, and the influence of circulating factors on endothelial cell nitric oxide and reactive oxygen species production. Overall, this trial will establish efficacy of high-resistance IMST for lowering BP and improving cardiovascular health in middle-aged and older adults with OSA. Methods: This is a single-site, double-blind, randomized clinical trial. A minimum of 92 and maximum of 122 male and female adults aged 50-80 years with OSA and above-normal BP will be enrolled. After completion of baseline assessments, subjects will be randomized in a 1:1 ratio to participate in either high-resistance or sham (low-resistance) control IMST, performed at home, 5 min/day, 5 days/week, for 24 weeks. Repeat assessments will be taken after the 24-week intervention, and after 4 and 12 weeks of free living. Discussion: This study is designed to assess the effects of 24 weeks of IMST on BP and vascular function. The results will characterize the extent to which IMST can reduce BP when performed over longer periods (i.e., 6 months) than have been assessed previously. Additionally, this study will help to determine underlying mechanisms driving IMST-induced BP reductions that have been reported previously. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (Registration Number: NCT04932447; Date of registration June 21, 2021).

Time-Efficient Inspiratory Muscle Strength Training Lowers Blood Pressure and Improves Endothelial Function, NO Bioavailability, and Oxidative Stress in Midlife/Older Adults With Above-Normal Blood Pressure.

Background High-resistance inspiratory muscle strength training (IMST) is a novel, time-efficient physical training modality. Methods and Results We performed a double-blind, randomized, sham-controlled trial to investigate whether 6 weeks of IMST (30 breaths/day, 6 days/week) improves blood pressure, endothelial function, and arterial stiffness in midlife/older adults (aged 50-79 years) with systolic blood pressure ≥120 mm Hg, while also investigating potential mechanisms and long-lasting effects. Thirty-six participants completed high-resistance IMST (75% maximal inspiratory pressure, n=18) or low-resistance sham training (15% maximal inspiratory pressure, n=18). IMST was safe, well tolerated, and had excellent adherence (≈95% of training sessions completed). Casual systolic blood pressure decreased from 135±2 mm Hg to 126±3 mm Hg (P<0.01) with IMST, which was ≈75% sustained 6 weeks after IMST (P<0.01), whereas IMST modestly decreased casual diastolic blood pressure (79±2 mm Hg to 77±2 mm Hg, P=0.03); blood pressure was unaffected by sham training (all P>0.05). Twenty-four hour systolic blood pressure was lower after IMST versus sham training (P=0.01). Brachial artery flow-mediated dilation improved ≈45% with IMST (P<0.01) but was unchanged with sham training (P=0.73). Human umbilical vein endothelial cells cultured with subject serum sampled after versus before IMST exhibited increased NO bioavailability, greater endothelial NO synthase activation, and lower reactive oxygen species bioactivity (P<0.05). IMST decreased C-reactive protein (P=0.05) and altered select circulating metabolites (targeted plasma metabolomics) associated with cardiovascular function. Neither IMST nor sham training influenced arterial stiffness (P>0.05). Conclusions High-resistance IMST is a safe, highly adherable lifestyle intervention for improving blood pressure and endothelial function in midlife/older adults with above-normal initial systolic blood pressure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03266510.

Acute cardiovascular responses to a single bout of high intensity inspiratory muscle strength training in healthy young adults.

High intensity, low volume inspiratory muscle strength training (IMST) has favorable effects on casual systolic blood pressure and systemic vascular resistance. However, the acute effects of IMST on heart rate (HR), blood pressure (BP), and sympathetic regulation of vascular resistance and the trajectory of post exercise recovery are not known. We recruited 14 young adults (7 women/7 men, age: 22 ± 2 years) to perform a single bout of high intensity IMST (inspiratory resistance set at 75% of maximal inspiratory pressure) importantly, female and male subjects were matched in regard to the target inspiratory pressure and target inspiratory muscle work per breath. We recorded HR, beat-to-beat changes in BP and postganglionic, muscle sympathetic nerve activities (MSNA) continuously throughout baseline, a single bout of IMST (comprising five sets of 6 inspiratory efforts) and in recovery. We show that one bout of IMST does not effect a change in BP, however, it effects a significant increase in HR (68.4 ± 11.7 beats/min versus 85.4 ± 13.6 beats/min; P < 0.001) and a significant decline in MSNA (6.8 ± 1.1 bursts/15 s bin; P < 0.001 versus 3.6 ± 0.6 bursts/15 s bin) relative to baseline. Remarkably, among men MSNA rebounded to baseline levels within the first minute of recovery, however, in women, MSNA suppression persisted for 5 min. We show that in healthy young adults, high intensity, low volume respiratory training results in the acute suppression of MSNA. Importantly, MSNA suppression is of greater magnitude and longer duration in women than in men.NEW & NOTEWORTHY Previous studies show 6 weeks of high intensity, low volume inspiratory muscle strength training (IMST) lowers blood pressure (BP) and systemic vascular resistance in young adults. However, the acute response to IMST is unknown. We characterized BP, heart rate, and sympathetic nervous activity (SNA) in healthy young adults at baseline, during IMST, and in recovery. There was no acute effect of IMST on BP, however, there was significant IMST-related suppression of SNA that was of greater magnitude in women than men.

Inspiratory muscle strength training lowers blood pressure and sympathetic activity in older adults with OSA: a randomized controlled pilot trial.

Previous work has shown lowered casual blood pressure after just 6 wk of inspiratory muscle strength training (IMST), suggesting IMST as a potential therapeutic in the prevention/treatment of hypertension. In this study, we assessed the effects of IMST on cardiovascular parameters in older, overweight adults diagnosed with moderate and severe obstructive sleep apnea (OSA). Subjects were randomly assigned to one of two interventions 1) high-intensity IMST (n = 15, 75% maximal inspiratory pressure), or 2) a control intervention (n = 10, 15% maximum inspiratory pressure). Subjects in both groups trained at home completing 30 training breaths/day, 5 days/wk for 6 wk. Pre- and posttraining measures included maximal inspiratory pressure, casual and ambulatory blood pressures, spontaneous cardiac baroreflex sensitivity, and muscle sympathetic nerve activity. Men and women in the high-intensity IMST group exhibited reductions in casual systolic (SBP), diastolic (DBP), and mean arterial blood pressures (MAP) [SBP: -8.82 ± 4.98 mmHg; DBP: -4.69 ± 2.81 mmHg; and MAP: -6.06 ± 1.03 mmHg; P < 0.002] and nighttime SBP (pre: -12.00 ± 8.20 mmHg; P < 0.01). Muscle sympathetic nerve activities also were lower (-6.97 ± 2.29 bursts/min-1; P = 0.01 and -9.55 ± 2.42 bursts/100 heartbeats; P = 0.002) by week 6. Conversely, subjects allocated to the control group showed no change in casual blood pressure or muscle sympathetic nerve activity and a trend toward higher overnight blood pressures. A short course of high-intensity IMST may offer significant respiratory and cardiovascular benefits for older, overweight adults with OSA. For Clinical Trial Registration, see https://www.clinicaltrials.gov (Identifier: NCT02709941).NEW & NOTEWORTHY Older, obese adults with moderate-severe obstructive sleep apnea who perform 5 min/day high-intensity inspiratory muscle strength training (IMST) exhibit lowered casual and nighttime systolic blood pressure and sympathetic nervous outflow. In contrast, adults assigned to a control (low-intensity) intervention exhibit no change in casual blood pressure or muscle sympathetic nerve activity and a trend toward increased overnight blood pressure. Remarkably, adherence to IMST even among sleep-deprived and exercise-intolerant adults is high (96%).

Time-efficient physical training for enhancing cardiovascular function in midlife and older adults: promise and current research gaps.

Cardiovascular diseases (CVD) remain the leading cause of death in developed societies, and "midlife" (50-64 yr) and older (65+) men and women bear the great majority of the burden of CVD. Much of the increased risk of CVD in this population is attributable to CV dysfunction, including adverse changes in the structure and function of the heart, increased systolic blood pressure, and arterial dysfunction. The latter is characterized by increased arterial stiffness and vascular endothelial dysfunction. Conventional aerobic exercise training, as generally recommended in public health guidelines, is an effective strategy to preserve or improve CV function with aging. However, <40% of midlife and older adults meet aerobic exercise guidelines, due in part to time availability-related barriers. As such, there is a need to develop evidence-based time-efficient exercise interventions that promote adherence and optimize CV function in these groups. Two promising interventions that may meet these criteria are interval training and inspiratory muscle strength training (IMST). Limited research suggests these modes of training may improve CV function with time commitments of ≤60 min/wk. This review will summarize the current evidence for interval training and IMST to improve CV function in midlife/older adults and identify key research gaps and future directions.

Daily inspiratory muscle training lowers blood pressure and vascular resistance in healthy men and women.

NEW FINDINGS: What is the central question of this study? What impact does inspiratory muscle training have on systemic vascular resistance, cardiac output and baroreflex sensitivity in adult men and women? What is the main finding and its importance? Inspiratory muscle training exerts favorable effects on blood pressure, vascular resistance and perception of stress. This exercise format is well-tolerated and equally effective whether implemented in men or women. ABSTRACT: Previous work has shown that inspiratory muscle training (IMT) lowers blood pressure after a mere 6 weeks, identifying IMT as a potential therapeutic intervention to prevent or treat hypertension. Here, we explore the effects of IMT on respiratory muscle strength and select cardiovascular parameters in recreationally active men and women. Subjects were randomly assigned to IMT (n = 12, 75% maximal inspiratory pressure) or sham training (n = 13, 15% maximal inspiratory pressure) groups and underwent a 6-week intervention comprising 30 breaths day-1 , 5 days week-1 . Pre- and post-training measures included maximal inspiratory pressure and resting measures of blood pressure, cardiac output, heart rate, spontaneous cardiac baroreflex sensitivity and systemic vascular resistance. We evaluated psychological and sleep status via administration of the Cohen-Hoberman inventory of physical symptoms and the Epworth sleepiness scale. Male and female subjects in the IMT group showed declines in systolic/diastolic blood pressures (-4.3/-3.9 mmHg, P < 0.025) and systemic vascular resistance (-3.5 mmHg min l-1 , P = 0.008) at week 6. There was no effect of IMT on cardiac output (P = 0.722), heart rate (P = 0.795) or spontaneous cardiac baroreflex sensitivity (P = 0.776). The IMT subjects also reported fewer stress-related symptoms (pre- versus post-training, 12.5 ± 8.5 versus 7.2 ± 9.7, P = 0.025). Based on these results, we suggest that a short course of IMT confers significant respiratory and cardiovascular improvements and parallel (modest) psychological benefits in healthy men and women.

Association between Laryngeal Airway Aperture and the Discharge Rates of Genioglossus Motor Units.

We know very little about how muscles and motor units in one region of the upper airway are impacted by adjustments in an adjacent airway region. In this case, the focus is on regulation of the expiratory airstream by the larynx and how changes in laryngeal aperture impact muscle motor unit activities downstream in the pharynx. We selected sound production as a framework for study as it requires (i) sustained expiratory airflow, (ii) laryngeal airway regulation for production of whisper and voice, and (iii) pharyngeal airway regulation for production of different vowel sounds. We used these features as the means of manipulating expiratory airflow, pharyngeal, and laryngeal airway opening to compare the effect of each on the activation of genioglossus (GG) muscle motor units in the pharynx. We show that some GG muscle motor units (a) discharge stably on expiration associated with production of vowel sounds, (b) are exquisitely sensitive to subtle alterations in laryngeal airflow, and (c) discharge at higher firing rates in high flow vs. low flow conditions even when producing the same vowel sound. Our results reveal subtle changes in GG motor unit discharge rates that correlate with changes imposed at the larynx, and which may contribute to the regulation of the expiratory airstream.

Evaluating the control: minipump implantation and breathing behavior in the neonatal rat.

We evaluated genioglossus (GG) gross motoneuron morphology, electromyographic (EMG) activities, and respiratory patterning in rat pups allowed to develop without interference (unexposed) and pups born to dams subjected to osmotic minipump implantation in utero (saline-exposed). In experiment 1, 48 Sprague-Dawley rat pups (Charles-River Laboratories), ages postnatal day 7 (P7) through postnatal day 10 (P10), were drawn from two experimental groups, saline-exposed (n = 24) and unexposed (n = 24), and studied on P7, P8, P9, or P10. Pups in both groups were sedated (Inactin hydrate, 70 mg/kg), and fine-wire electrodes were inserted into the GG muscle of the tongue and intercostal muscles to record EMG activities during breathing in air and at three levels of normoxic hypercapnia [inspired CO2 fraction (FiCO2 ): 0.03, 0.06, and 0.09]. Using this approach, we assessed breathing frequency, heart rate, apnea type, respiratory event types, and respiratory stability. In experiment 2, 16 rat pups were drawn from the same experimental groups, saline-exposed (n = 9) and unexposed (n = 7), and used in motoneuron-labeling studies. In these pups a retrograde dye was injected into the GG muscle, and the brain stems were subsequently harvested and sliced. Labeled GG motoneurons were identified with microscopy, impaled, and filled with Lucifer yellow. Double-labeled motoneurons were reconstructed, and the number of primary projections and soma volumes were calculated. Whereas pups in each group exhibited the same number (P = 0.226) and duration (P = 0.093) of respiratory event types and comparable motoneuron morphologies, pups in the implant group exhibited more central apneas and respiratory instability relative to pups allowed to develop without interference.

Inspiratory Muscle Training Improves Sleep and Mitigates Cardiovascular Dysfunction in Obstructive Sleep Apnea.

STUDY OBJECTIVES: New and effective strategies are needed to manage the autonomic and cardiovascular sequelae of obstructive sleep apnea (OSA). We assessed the effect of daily inspiratory muscle strength training (IMT) on sleep and cardiovascular function in adults unable to use continuous positive airway pressure (CPAP) therapy. METHODS: This is a placebo-controlled, single-blind study conducted in twenty four adults with mild, moderate, and severe OSA. Subjects were randomly assigned to placebo or inspiratory muscle strength training. Subjects in each group performed 5 min of training each day for 6 w. All subjects underwent overnight polysomnography at intake and again at study close. RESULTS: We evaluated the effects of placebo training or IMT on sleep, blood pressure, and plasma catecholamines. Relative to placebo-trained subjects with OSA, subjects with OSA who performed IMT manifested reductions in systolic and diastolic blood pressures (-12.3 ± 1.6 SBP and -5.0 ± 1.3 DBP mmHg; P < 0.01); plasma norepinephrine levels (536.3 ± 56.6 versus 380.6 ± 41.2 pg/mL; P = 0.01); and registered fewer nighttime arousals and reported improved sleep (Pittsburgh Sleep Quality Index scores: 9.1 ± 0.9 versus 5.1 ± 0.7; P = 0.001). These favorable outcomes were achieved without affecting apneahypopnea index. CONCLUSIONS: The results are consistent with our previously published findings in normotensive adults but further indicate that IMT can modulate blood pressure and plasma catecholamines in subjects with ongoing nighttime apnea and hypoxemia. Accordingly, we suggest IMT offers a low cost, nonpharmacologic means of improving sleep and blood pressure in patients who are intolerant of CPAP.

Daily respiratory training with large intrathoracic pressures, but not large lung volumes, lowers blood pressure in normotensive adults.

Inspiratory muscle training holds promise as a non-pharmacologic treatment that can improve respiratory muscle strength, reduce blood pressure, and improve autonomic balance in hypertensive patients. There is a gap in knowledge regarding the specific respiratory stimulus that gives rise to these favorable outcomes. We implemented five respiratory training protocols that differed in the magnitude and direction of the lung volumes and/or intrathoracic pressures generated by subjects in training. Normotensive adults were randomly assigned to each group and trained daily for 6 weeks. Pre-post and weekly measures of blood pressure showed significant declines in systolic [-8.96 mmHg (95% CI, 7.39-10.53)] and diastolic [-5.25 mmHg (95% CI, 3.67-6.83)] blood pressures for subjects who trained with large positive or negative intrathoracic pressures. Subjects who trained with modest intrathoracic pressures or large lung volumes saw no improvement in blood pressure (P > 0.3). Large intra-thoracic pressures are the specific respiratory stimulus underpinning breathing training related improvements in blood pressure.

A comprehensive assessment of genioglossus electromyographic activity in healthy adults.

The genioglossus (GG) is an extrinsic muscle of the human tongue that plays a critical role in preserving airway patency. In the last quarter century, >50 studies have reported on respiratory-related GG electromyographic (EMG) activity in human subjects. Remarkably, of the studies performed, none have duplicated subject body position, electrode recording locations, and/or breathing task(s), making interpretation and integration of the results across studies extremely challenging. In addition, more recent research assessing lingual anatomy and muscle contractile properties has identified regional differences in muscle fiber type and myosin heavy chain expression, giving rise to the possibility that the anterior and posterior regions of the muscle fulfill distinct functions. Here, we assessed EMG activity in anterior and posterior regions of the GG, across upright and supine, in rest breathing and in volitionally modulated breathing tasks. We tested the hypotheses that GG EMG is greater in the posterior region and in supine, except when breathing is subject to volitional modulation. Our results show differences in the magnitude of EMG (%regional maximum) between anterior and posterior muscle regions (7.95 ± 0.57 vs. 11.10 ± 0.99, respectively; P < 0.001), and between upright and supine (8.63 ± 0.73 vs. 10.42 ± 0.90, respectively; P = 0.008). Although the nature of a task affects the magnitude of EMG (P < 0.001), the effect is similar for anterior and posterior muscle regions and across upright and supine (P > 0.2).

Developmental nicotine exposure adversely effects respiratory patterning in the barbiturate anesthetized neonatal rat.

Neonates at risk for sudden infant death syndrome (SIDS) are hospitalized for cardiorespiratory monitoring however, monitoring is costly and generates large quantities of averaged data that serve as poor predictors of infant risk. In this study we used a traditional autocorrelation function (ACF) testing its suitability as a tool to detect subtle alterations in respiratory patterning in vivo. We applied the ACF to chest wall motion tracings obtained from rat pups in the period corresponding to the mid-to-end of the third trimester of human pregnancy. Pups were drawn from two groups: nicotine-exposed and saline-exposed at each age (i.e., P7, P8, P9, and P10). Respiratory-related motions of the chest wall were recorded in room air and in response to an arousal stimulus (FIO2 14%). The autocorrelation function was used to determine measures of breathing rate and respiratory patterning. Unlike alternative tools such as Poincare plots that depict an averaged difference in a measure breath to breath, the ACF when applied to a digitized chest wall trace yields an instantaneous sample of data points that can be used to compare (data) points at the same time in the next breath or in any subsequent number of breaths. The moment-to-moment evaluation of chest wall motion detected subtle differences in respiratory pattern in rat pups exposed to nicotine in utero and aged matched saline-exposed peers. The ACF can be applied online as well as to existing data sets and requires comparatively short sampling windows (∼2 min). As shown here, the ACF could be used to identify factors that precipitate or minimize instability and thus, offers a quantitative measure of risk in vulnerable populations.

Neural drive to respiratory muscles in the spontaneously breathing rat pup.

The neonatal rodent serves as useful and appropriate model within which to study respiratory system development. Despite an extensive literature that documents respiratory control in vitro, in vivo studies have relied upon whole body plethysmography to determine measures of respiratory frequency and tidal volume. However, plethysmography restricts access to the animal and thus, respiratory muscle electromyographic (EMG) activities have not been recorded in these studies previously. Electromyography yields accurate information about neural respiratory center output to the musculature and therefore, about the control of breathing in the intact animal. In this case, we documented neural drive to respiratory pump and upper airway muscles, electrocardiogram (ECG) and chest wall motions in rat pups up to 10 days of age noting sighs, spontaneous central apneas and hypopneas in room air and with successive increments in fractional inspired CO2 (FICO2). Our findings underscore the advantages of EMG recordings for purposes of determining the magnitude and distribution of neural drive to respiratory muscles and for characterizing the full range of breathing behaviors exhibited by rats in the early postnatal period.