Resistive Breathing Research Articles

Dynamic cerebral autoregulation is preserved during orthostasis and intrathoracic pressure regulation in healthy subjects: A pilot study.

Resistance breathing may restore cardiac output (CO) and cerebral blood flow (CBF) during hypovolemia. We assessed CBF and cerebral autoregulation (CA) during tilt, resistance breathing, and paced breathing in 10 healthy subjects. Blood velocities in the internal carotid artery (ICA), middle cerebral arteries (MCA, four subjects), and aorta were measured by Doppler ultrasound in 30° and 60° semi-recumbent positions. ICA blood flow and CO were calculated. Arterial blood pressure (ABP, Finometer), and end-tidal CO2 (ETCO2) were recorded. ICA blood flow response was assessed by mixed-models regression analysis. The synchronization index (SI) for the variable pairs ABP-ICA blood velocity, ABP-MCA velocities in 0.005-0.08 Hz frequency interval was calculated as a measure of CA. Passive tilting from 30° to 60° resulted in 12% decrease in CO (p = 0.001); ICA blood flow tended to fall (p = 0.04); Resistance breathing restored CO and ICA blood flow despite a 10% ETCO2 drop. ETCO2 and CO contributed to ICA blood flow variance (adjusted R2: 0.9, p < 0.0001). The median SI was low (<0.2) indicating intact CA, confirmed by surrogate date testing. The peak SI was transiently elevated during resistance breathing in the 60° position. Resistance breathing may transiently reduce CA efficiency. Paced breathing did not restore CO or ICA blood flow.

Acute cardiac autonomic and hemodynamic responses to resistive breathing: Effect of loading type and intensity.

This study aimed to assess the acute impact of distinct loading breathing types and intensities on cardiac autonomic function and hemodynamic responses in healthy young adults. A randomized, crossover trial involved 28 participants who underwent inspiratory resistive breathing, expiratory resistive breathing (ERB) and combined resistive breathing, each at 30% and 60% of maximal respiratory pressures. Data on heart rate variability (HRV) and hemodynamic parameters were collected during each trial. The study revealed significant main and interaction effects for both the performed task and the intensity across all measured variables (all p < 0.001). ERB at 60% load demonstrated significantly higher HRV values in the standard deviation of normal-to-normal RR intervals, the square root of the mean squared difference of successive normal-to-normal RR intervals and high-frequency power, as well as significantly lower values in heart rate, stroke volume, stroke volume index, cardiac output, cardiac index, end-diastolic volume and end-diastolic volume index, compared to other loaded protocols (all p < 0.001). These findings highlight the acute effect of type-specific and load-dependent resistive breathing on cardiac autonomic and hemodynamic functions, where ERB at 60% intensity showed the most significant cardiovagal modulation while causing the least hemodynamic alterations.

Effects of Yogic Breathing Techniques on Respiratory Function and Breathing Patterns at High Altitude

Background: Practices involving resistive breathing have been shown to enhance endurance and performance in competitive athletes. However, there is still little research on how pranayama or yogic breathing techniques (YBP) might help professional athletes improve their respiratory endurance and performance. Aim: The objective of the current research was to assess how yoga breathing practices affected competitive athletes’ respiratory function. Methodology: A total of 60 (30 male and 30 female) athletes were included and were divided into two groups; control and experimental. 30 individuals were randomly assigned in both the groups. The experimental group received daily instruction in yogic breathing techniques for one hour for six months. The control group received the same daily schedule (normal exercise). Various anthropometric measurements and spirometry measurements such as FVC, FEV1, PEFR, and the FEV1/FVC ratio both before and after yoga intervention in both the groups were measured. Result: The result showed significant increase in FVC level in control (3.51L) and experimental group (3.64L) P&lt;0.05). A significant increase in FEV1 (3.43L) and PEF (534.18L/s) levels were also observed post-test of experimental groups (P&lt;0.05), whereas the increase was non-significant in control group (P&gt;0.05). Non-significant results were also observed in FEV1/FVC ratio in both control and experimental group (P&lt;0.05). Conclusions: At high altitudes, yoga practices may beneficial for athletes in bringing about favorable psychological changes among low landers athletes.

Effect of breather device on respiratory muscle strength and quality of life in coronary artery bypass grafting patients: A randomised control trial protocol

Coronary artery bypass surgery is widely spread and done for multiple vessel disease, and still a well-established therapy option for coronary artery disease. Reduced respiratory muscle strength has been linked to decreased functional capacity in heart surgery, which has been linked to a prolonged recovery period for lung functions and onset of physical deconditioning, which can last for more than a week. Other common postoperative complications include urinary tract infections, renal failure, limb ischemia, pleural effusion, and hematologic abnormalities. Alterations in lung capacity and size, malfunction of the alveoli, decrease in the central respiratory stimulus, and mechanical issues with thoracic function are all brought on by respiratory consequences. Therefore, to prevent or reduce postoperative pulmonary complications, it is typically advised that patients who have had heart surgery engage in breathing exercises and chest physical therapy. The Breather is a breathing apparatus that uses resistance breathing through various-sized orifices to strengthen respiratory muscles. In addition to healthy people and athletes, breather devices can be used for training, therapy, prevention, or rehabilitation of a variety of pulmonary and other disorders. As there is limited literature showing the efficacy of a breather device in coronary artery bypass grafting (CABG) patients, therefore a need for a study to find the efficacy of a breather device in assessing strength of respiratory muscle and quality of life in CABG patients. Treatment will be given for three weeks with five sessions per week twice a day. Pre- and post-treatment outcomes will be noted. In this study, results are expected to prove the Breather device is as effective or more effective than conventional chest physiotherapy for refining respiratory muscle strength and quality of life. CTRI registration: CTRI/2023/05/053052

Synergistic Effects of Resistive Breathing on Endotoxin-Induced Lung Injury in Mice.

Resistive breathing (RB) is characterized by forceful contractions of the inspiratory muscles, mainly the diaphragm, resulting in large negative intrathoracic pressure and mechanical stress imposed on the lung. We have shown that RB induces lung injury in healthy animals. Whether RB exerts additional injurious effects when added to pulmonary or extrapulmonary lung injury is unknown. Our aim was to study the synergistic effect of RB on lipopolysaccharide (LPS)-induced lung injury. C57BL/6 mice inhaled an LPS aerosol (10mg/3mL) or received an intraperitoneal injection of LPS (10 mg/kg). Mice were then anaesthetized, the trachea was surgically exposed, and a nylon band of a specified length was sutured around the trachea, to provoke a reduction of the surface area at 50%. RB through tracheal banding was applied for 24 hours. Respiratory system mechanics were measured, BAL was performed, and lung sections were evaluated for histological features of lung injury. LPS inhalation increased BAL cellularity, mainly neutrophils (p < 0.001 to ctr), total protein and IL-6 in BAL (p < 0.001 and p < 0.001, respectively) and increased the lung injury score (p = 0.001). Lung mechanics were not altered. Adding RB to inhaled LPS further increased BAL cellularity (p < 0.001 to LPS inh.), total protein (p = 0.016), lung injury score (p = 0.001) and increased TNFa levels in BAL (p = 0.011). Intraperitoneal LPS increased BAL cellularity, mainly macrophages (p < 0.001 to ctr.), total protein levels (p = 0.017), decreased static compliance (p = 0.004) and increased lung injury score (p < 0.001). Adding RB further increased histological features of lung injury (p = 0.022 to LPS ip). Resistive breathing exerts synergistic injurious effects when combined with inhalational LPS-induced lung injury, while the additive effect on extrapulmonary lung injury is less prominent.

Inspiratory pressure waveform influences time to failure, respiratory muscle fatigue, and metabolism during resistive breathing.

Increased ventilatory work beyond working capacity of the respiratory muscles can induce fatigue, resulting in limited respiratory muscle endurance (Tlim ). Previous resistive breathing investigations all applied square wave inspiratory pressure as fatigue-inducing pattern. Spontaneous breathing pressure pattern more closely approximate a triangle waveform. This study aimed at comparing Tlim , maximal inspiratory pressure (PImax ), and metabolism between square and triangle wave breathing. Eight healthy subjects (Wei = 76 ± 10 kg, H = 181 ± 7.9 cm, age = 33.5 ± 4.8 years, sex [F/M] = 1/7) completed the study, comprising two randomized matched load resistive breathing trials with square and triangle wave inspiratory pressure waveform. Tlim decreased with a mean difference of 8 ± 7.2 min (p = 0.01) between square and triangle wave breathing. PImax was reduced following square wave (p = 0.04) but not for triangle wave breathing (p = 0.88). Higher VO2 was observed in the beginning and end for the triangle wave breathing compared with the square wave breathing (p = 0.036 and p = 0.048). Despite higher metabolism, Tlim was significantly longer in triangle wave breathing compared with square wave breathing, showing that the pressure waveform has an impact on the function and endurance of the respiratory muscles.

Short-Term L-Citrulline Supplementation Does Not Affect Inspiratory Muscle Oxygenation and Respiratory Performance in Older Adults

In sports nutrition, nitric oxide (NO•) precursors such as L-citrulline are widely used to enhance NO• bioavailability, which is considered an ergogenic aid. Our study aimed to examine the effect of short-term L-citrulline supplementation on respiratory muscles' performance, fatigue, and oxygenation in older adults. Fourteen healthy older males took 6 g of L-citrulline or a placebo for seven days in a double-blind crossover design. Pulmonary function via spirometry (i.e., forced expired volume in 1 s (FEV1), forced vital capacity (FVC), and their ratio)), fractional exhaled nitric oxide (NO•), maximal inspiratory pressure (MIP), rate of perceived exertion, and sternocleidomastoid muscle oxygenation (i.e., oxyhemoglobin (Δ[O2Hb]) and de-oxyhemoglobin (Δ[HHb]), total hemoglobin concentration (Δ[tHb]), and tissue saturation index (TSI%)) were evaluated at baseline, after seven days of L-citrulline supplementation, and after incremental resistive breathing to task failure of the respiratory muscles. The exhaled NO• value was only significantly increased after the supplementation (26% p < 0.001) in the L-citrulline condition. Pulmonary function, MIP, rate of perceived exertion, and sternocleidomastoid muscle oxygenation were not affected by the L-citrulline supplementation. In the present study, although short-term L-citrulline supplementation increased exhaled NO•, no ergogenic aids were found on the examined parameters at rest and after resistive breathing to task failure in older adults.

Sex differences in blood pressure and inactive limb blood flow responses during dynamic leg exercise with increased inspiratory muscle work.

We hypothesized that, compared with young males, young females have a smaller decrease in blood flow to the inactive limb, accompanied by a smaller increase in arterial blood pressure, during dynamic exercise with increased inspiratory muscle work. Young males and females performed dynamic knee-extension and -flexion exercises for 10 min (spontaneous breathing for 5 min and voluntary hyperpnoea with or without inspiratory resistance for 5 min). Mean arterial blood pressure (MAP) and mean blood flow (MBF) in the brachial artery were continuously measured by means of finger photoplethysmography and Doppler ultrasound, respectively. No sex differences were found in the ΔMAP and ΔMBF (Δ: from baseline) during exercise without inspiratory resistance. In contrast, the ΔMAP during exercise with inspiratory resistive breathing was greater (P < 0.05) in males (+31.3 ± 2.1 mmHg, mean ± SE) than females (+18.9 ± 3.2 mmHg). The MBF during exercise with inspiratory resistance did not change in males (-4.4 ± 10.6 mL/min), whereas it significantly increased in females (+25.2 ± 15.4 mL/min). These results suggest that an attenuated inspiratory muscle-induced metaboreflex in young females affects blood flow distribution during submaximal dynamic leg exercise.

Inspiratory and leg muscle blood flows during inspiratory muscle metaboreflex activation in heart failure with preserved ejection fraction.

The purpose of this study was to determine the cardiovascular consequences elicited by activation of the inspiratory muscle metaboreflex in patients with heart failure with preserved ejection fraction (HFpEF) and controls. Patients with HFpEF (n = 15; 69 ± 10 yr; 33 ± 4 kg/m2) and controls (n = 14; 70 ± 8 yr; 28 ± 4 kg/m2) performed an inspiratory loading trial at 60% maximal inspiratory pressure (PIMAX) until task failure. Mean arterial pressure (MAP) was measured continuously. Near-infrared spectroscopy and bolus injections of indocyanine green dye were used to determine the percent change in blood flow index (%ΔBFI) from baseline to the final minute of inspiratory loading in the vastus lateralis and sternocleidomastoid muscles. Vascular resistance index (VRI) was calculated. Time to task failure was shorter in HFpEF than in controls (339 ± 197 s vs. 626 ± 403 s; P = 0.02). Compared with controls, patients with HFpEF had a greater increase from baseline in MAP (16 ± 7 vs. 10 ± 6 mmHg) and vastus lateralis VRI (76 ± 45 vs. 32 ± 19%) as well as a greater decrease in vastus lateralis %ΔBFI (-32 ± 14 vs. -17 ± 9%) (all, P < 0.05). Sternocleidomastoid %ΔBFI normalized to absolute inspiratory pressure was higher in HFpEF compared with controls (8.0 ± 5.0 vs. 4.0 ± 1.9% per cmH2O·s; P = 0.03). These data indicate that patients with HFpEF exhibit exaggerated cardiovascular responses with inspiratory muscle metaboreflex activation compared with controls.NEW & NOTEWORTHY Respiratory muscle dysfunction is thought to contribute to exercise intolerance in heart failure with preserved ejection fraction (HFpEF); however, the underlying mechanisms are unknown. In the present study, patients with HFpEF had greater increases in leg muscle vascular resistance index and greater decreases in leg muscle blood flow index compared with controls during inspiratory resistive breathing (to activate the metaboreflex). Furthermore, respiratory muscle blood flow index responses normalized to pressure generation during inspiratory resistive breathing were exaggerated in HFpEF compared with controls.

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.

Changes In Splanchnic Blood Flow And Blood Pressure During Inspiratory Resistive Breathing

PURPOSE: The hyperpnea during whole-body heavy exercise leads to an increase in respiratory muscle work, which is associated with cardiovascular regulations during exercise (i.e., respiratory muscle metaboreflex). In resting condition, blood flow to inactive limbs is reduced with inspiratory resistive breathing. Furthermore, increasing the work of breathing during dynamic exercise influences inactive limb blood flow. Therefore, it is conceivable that the respiratory muscle-induced metaboreflex is associated with blood flow redistribution during exercise. Redistribution of blood flow is also associated with splanchnic blood flow as well as inactive blood flow. However, influence of respiratory muscle metaboreflex on splanchnic blood flow in humans remains unknown. We hypothesized that blood flow to splanchnic organs would reduce via respiratory muscle-induced metaboreflex. METHODS: Ten healthy young men (20.2 ± 0.4 yrs, mean ± SE) performed two voluntary hyperventilation tests (tidal volume of 40% of vital capacity, a breathing frequency of 40 breaths/min and inspiratory duty cycle of 50%). One trial was voluntary hyperventilation with inspiratory resistance (about 40% of maximal inspiratory pressure), and the trial was terminated when the subject could not maintain the target ventilation (the resistance trial), and the other one was voluntary hyperventilation without inspiratory resistance until the same time as the resistance trial (the non-resistance trial). During trials, mean arterial blood pressure (MAP) was measured using finger photoplethysmography, and celiac artery blood flow was recorded by Doppler ultrasonography. RESULTS: MAP increased progressively and was higher (P < 0.05) in the resistance trial (100.5 ± 4.4 mmHg) than in the non-resistance trial (92.8 ± 2.0 mmHg) at the end of trial. Celiac artery blood flow decreased gradually from baseline value in the resistance trial (469.3 ± 47.6 mL/min), whereas did not change in the non-resistance trial (605.7 ± 56.2 mL/min). Celiac artery vascular conductance was lower in the resistance trial (4.8 ± 0.6 mL/min/mmHg) than in the non-resistance trial (6.6 ± 0.6 mL/min/mmHg, P < 0.05). CONCLUSIONS: These results suggest that increasing work of breathing affects the splanchnic circulation, via respiratory muscle-induced metaboreflex.

Influence of continuous inspiratory resistive breathing trials on corticospinal excitability of lower limb muscles during isometric contraction

ABSTRACT BACKGROUND Increased work of breathing or fatigue of respiratory muscles has been suggested to reduce exercise performance. PURPOSE The present study investigated the effects of continuous inspiratory resistive breathing (IRB) on the responsiveness of corticospinal pathway innervating the vastus lateralis (VL) to determine whether respiratory muscle fatigue affects the central motor output to exercising limb muscles. METHODS Eight subjects underwent a 6-min IRB trial three times (IRB1–3) in two experiments. During each IRB trial, the subjects performed voluntary hyperventilation through a mask attached with an inspiratory resistive load (approximately 30% of maximal inspiratory pressure (PImax)). In Experiment 1, PImax was measured at baseline and after each IRB trial. In Experiment 2, VL responses to transcranial magnetic stimulation (motor evoked potentials (MEPs) and cortical silent periods were assessed during 5 s isometric knee extension at an intensity of 15% of the maximal voluntary contraction over the same time course as in Experiment 1. RESULTS PImax decreased from baseline after IRB2 and IRB3 (P < 0.05). MEPs increased from baseline after IRB1 and IRB2 (P < 0.05), whereas MEPs after IRB3 were not significantly different from baseline. Cortical silent periods did not change from baseline after IRB1 and IRB2, whereas cortical silent periods after IRB3 increased from baseline (P < 0.05). CONCLUSION These results suggest that as inspiratory muscle fatigue progresses, the corticospinal tract controlling the lower limb muscles can shift from excitatory dominance to inhibitory dominance as a whole, affecting the central motor output to working limb muscles.

INSPIRATORY PRESSURE PATTERN AFFECTS RESPIRATORY MUSCLE FATIGUE DURING RESISTIVE BREATHING

TYPE: Late Breaking Abstract TOPIC: Pulmonary Physiology PURPOSE: The esophageal pressure (Peso) based tension-time index (TTI) is the reference technique for breathing effort assessment (Bellemare and Grassino. J Appl Physiol, 1982). TTI estimation entails measurement of the timing and effort of breathing and predicts time to fatigue during resistive breathing (Tlim). Effect of TTI on Tlim has been estimated using pressure square wave breathing. This cross-over study compares Tlim between square wave and more natural triangle wave breathing. METHODS: Four healthy subjects (W=70±9kg, H=176±4cm, age=31.7±6yr) were enrolled after informed consent. Subjects were fitted with a double-balloon nasogastric catheter. Two trials were performed, separated by >4 days of rest. Subjects were randomized to Peso square or triangle wave breathing with a target of mean 50% maximal inspiratory pressure (Pmax), Vt∼800ml, 12b/min, ti/ttot of 0.5 and through a resistance. Pmax was determined using magnetic phrenic nerve stimulation. Subjects reported modified Borg (0-10) every 5min. Tlim was decided when subjects could not maintain Peso target. RESULTS: Mean Tlim was 30.8min and 40.1min for square to triangle wave breathing, with a triangle-square difference of 9.2min (range:3-18.5min). Mean Borg was 5.2, 7 and 8.2 and 4.7, 7, 8.2 for square and triangle wave. CONCLUSIONS: Healthy subjects are able to sustain resistive breathing at the same average load for longer during a more natural breathing pattern compared to square wave breathing. CLINICAL IMPLICATIONS: If TTI is used to evaluate breathing effort, as preformed during weaning from mechanical ventilation or readiness to extubation, current TTI thresholds defined from square wave breathing might underestimate the patients’ ability to perform breathing. DISCLOSURE: No significant relationships. KEYWORD: Respiratory Muscle Fatigue

Resistance Breathing and Sympathetic Nerve Activity During Simulated Hemorrhage in Humans

BackgroundResistance breathing amplifies the respiratory pump during inspiration, so may be an effective intervention for treatment of hemorrhagic injuries. In animal studies of actual hemorrhage, and human studies of simulated hemorrhage, resistance breathing protects arterial pressure, and improves tolerance to this stress. Anecdotally, resistance breathing also increases the coupling between sympathetic nerve activity and arterial pressure. The impact of resistance breathing on overall sympathetic nerve activity, however, has not been examined. We tested the hypothesis that resistance breathing increases sympathetic nerve activity during simulated hemorrhage in healthy humans.MethodsLower body negative pressure (LBNP) was used to simulate hemorrhage in five human subjects (3M, 2F; 29.2 ± 6.8 y). Two experiments were conducted (randomized order): 1) a control condition in which LBNP was applied at 3 mmHg/min until the onset of presyncope, and 2) a resistance breathing condition in which the same LBNP protocol was used, but subjects breathed through a resistance device (set at ‐7 cm.H2O) during the final stages of the protocol. Arterial pressure and muscle sympathetic nerve activity (MSNA) of the radial nerve were monitored continuously. Bursts frequency (bursts/min) and burst incidence (burst/ 100 heart beats) were used to quantify MSNA. Coupling between diastolic arterial pressure (DAP) and MSNA was assessed by transfer function analysis coherence within the low frequency range (0.04‐0.15 Hz). Two‐way repeated measures ANOVAs were conducted for assessment of responses in the control and resistance breathing conditions, between baseline and at matched time points late in the LBNP protocol.ResultsWhile LBNP induced increases in both MSNA burst frequency (P=0.003) and burst incidence (P=0.06), there was no effect of resistance breathing on MSNA for either index during LBNP (control, 57.9 ± 25.9 bursts/min vs. resistance breathing, 50.6 ± 21.7 bursts/min, P=0.99; control, 55.6 ± 25.6 b/100 heart beats vs. resistance breathing, 42.3 ± 18.3 b/100 heart beats, P=0.42). Additionally, there was no effect of resistance breathing on DAP (control, 73.2 ± 9.9 mmHg vs. resistance breathing, 72.8 ± 4.4 mmHg; P=0.99), or coherence between MSNA and DAP during LBNP (control, 0.53 ± 0.21 vs. resistance breathing, 0.69 ± 0.17; P=0.46).ConclusionContrary to our hypothesis, resistance breathing had no effect on sympathetic nerve activity during LBNP. A limitation of this study is the low sample size (N=5), and high variability of MSNA. Future investigations with a larger sample size are needed to determine if respiratory dynamics can influence the coupling between MSNA and arterial pressure.

High‐intensity, low‐volume inspiratory muscle strength training blunts the cardiovascular response to constant load respiratory testing

Previous studies indicate inspiratory muscle strength training (IMST) may attenuate blood pressure (BP) and heart rate (HR) responsiveness to sustained respiratory muscle work. However, these previous studies used a less vigorous IMST intervention and did not have subjects gauge perception of respiratory effort. Our objective in this study was to evaluate the effects of 6 weeks high intensity (75% maximum inspiratory pressure), low volume (5 sets of 6 breaths/day) IMST on BP and HR responses to a resistive breathing trial (RBT) to exhaustion (target pressure = 65% of maximal inspiratory pressure or PImax; duty cycle = 0.7; breathing frequency matched to eupnea). We recruited 10 (7M; 3F) healthy young adults to complete two RBT, pre‐ and then again post‐, 6 weeks IMST. Throughout the RBT we assessed beat‐to‐beat changes in BP and HR, inspiratory pressure, respiratory muscle work (mmHg.s) and recorded participant ratings of perceived exertion (RPE) via the Borg scale. We report significant IMST‐related improvements in endurance time (PRE: 362.0 ±46.6s vs. POST: 663.8 ±110.3s, p=0.003) and respiratory muscle work (PRE: ‐9445 ±1562mmHg.s vs. POST: ‐16648 ±3761mmHg.s, p=0.069). Remarkably, despite significant gains in work and endurance, the latter stages of the post RBT were characterized by a reduced cardiovascular responsiveness (i.e., SBP, DBP and HR) and lower RPE, consistent with a blunting of the metaboreflex.

TRPV4 Inhibition Exerts Protective Effects Against Resistive Breathing Induced Lung Injury.

IntroductionTRPV4 channels are calcium channels, activated by mechanical stress, that have been implicated in the pathogenesis of pulmonary inflammation. During resistive breathing (RB), increased mechanical stress is imposed on the lung, inducing lung injury. The role of TRPV4 channels in RB-induced lung injury is unknown.Materials and MethodsSpontaneously breathing adult male C57BL/6 mice were subjected to RB by tracheal banding. Following anaesthesia, mice were placed under a surgical microscope, the surface area of the trachea was measured and a nylon band was sutured around the trachea to reduce area to half. The specific TRPV4 inhibitor, HC-067047 (10 mg/kg ip), was administered either prior to RB and at 12 hrs following initiation of RB (preventive) or only at 12 hrs after the initiation of RB (therapeutic protocol). Lung injury was assessed at 24 hrs of RB, by measuring lung mechanics, total protein, BAL total and differential cell count, KC and IL-6 levels in BAL fluid, surfactant Protein (Sp)D in plasma and a lung injury score by histology.ResultsRB decreased static compliance (Cst), increased total protein in BAL (p < 0.001), total cell count due to increased number of both macrophages and neutrophils, increased KC and IL-6 in BAL (p < 0.001 and p = 0.01, respectively) and plasma SpD (p < 0.0001). Increased lung injury score was detected. Both preventive and therapeutic HC-067047 administration restored Cst and inhibited the increase in total protein, KC and IL-6 levels in BAL fluid, compared to RB. Preventive TRPV4 inhibition ameliorated the increase in BAL cellularity, while therapeutic TRPV4 inhibition exerted a partial effect. TRPV4 inhibition blunted the increase in plasma SpD (p < 0.001) after RB and the increase in lung injury score was also inhibited.ConclusionTRPV4 inhibition exerts protective effects against RB-induced lung injury.

Wearables, Respiratory Rehabilitation, Acute Myocardial Infarction and Frailty, and High-Intensity Respiratory Muscle Training

Wearables, Respiratory Rehabilitation, Acute Myocardial Infarction and Frailty, and High-Intensity Respiratory Muscle Training

Abstract 10528: Exaggerated Inspiratory Muscle Metaboreflex in Heart Failure with Preserved Ejection Fraction

Introduction: Heart failure patients with preserved ejection fraction (HFpEF) may exhibit inspiratory muscle dysfunction potentially contributing to exercise intolerance. Activation of neural afferents in response to inspiratory muscle contraction (metaboreflex) elicits increases in mean arterial pressure (MAP) and leg vascular resistance (LVR) through enhanced sympathetic outflow leading to decreases in leg blood flow (LBF) in healthy humans. It is unknown if HFpEF patients exhibit exaggerated cardiovascular responses to inspiratory muscle metaboreflex activation. Hypothesis: We hypothesize that patients with HFpEF will exhibit a greater increase in MAP and LVR with a decrease in LBF during inspiratory muscle metaboreflex activation than controls. Methods: HFpEF patients (n=15, 10M/5W, 69±10 yrs; 33±4 kg/m2) and controls (n=14; 10M/4W; 70±8 yrs; 28±4 kg/m2) performed inspiratory resistive breathing tasks (IRBT) at 2% and 60% of their maximal inspiratory pressure. During the IRBTs, the breathing frequency was 20 breaths/min with a 50% duty cycle. At rest and during the IRBTs, MAP was measured by photoplethysmography, venous norepinephrine was measured, LBF was measured by near-infrared spectroscopy and indocyanine green dye injections, and LVR was calculated. Results: During the 2% IRBT, there were no differences between groups in the changes from rest in MAP (HFpEF: 2±4 vs. CTL: 3±4 mmHg) or LBF (HFpEF: 1±14 vs. CTL: 1±12%) (both, p&gt;0.05). During the 60% IRBT, venous norepinephrine increased from rest in HFpEF and controls (p&lt;0.05), while no differences existed between groups (p&gt;0.05). During the 60% IRBT, HFpEF patients, compared to controls, exhibited a greater increase from rest in MAP (HFpEF: 16±7 vs. CTL: 10±6 mmHg) and LVR (HFpEF: 76±45 vs. CTL: 32±19%) coupled with a greater decrease in LBF (HFpEF: -32±14 vs. CTL: -17±9%) (all, p&lt;0.05). Conclusions: These data indicate that patients with HFpEF exhibit exaggerated cardiovascular responses with inspiratory muscle metaboreflex activation compared to healthy individuals. These findings have important implications for the integrative physiology of exercise in HFpEF patients.

Pathophysiological mechanisms of resistive breathing

AIM: This study aimed to explore the pathophysiological mechanisms of resistive breathing by using a model of a conditioned respiratory reflex to external resistance to breathing.&#x0D; MATERIALS AND METHODS: Inspiratory resistive loads were used 11, 28, 54, and 78 cmAq/l/s to model a conditioned respiratory reflex. External respiration was parametrized on the basis of the analysis of motor and ventilatory outputs. Conditioned signals were pure sounds exceeding the threshold of perception by 10 db at 2000 Hz frequency. All the test persons were divided into two groups (large and small groups) according to the initial reinforcement value. (1) In the large group (37 individuals), the conditioned reflex was formed from 11 cmAq/l/s that was subsequently increased stepwise in the load to 76 cmAq/l/s. (2) In the small group (18 individuals), the initial reinforcements were different gradations of resistive loads, with a stepwise transition to the other parameters of an unconditioned stimulus. The period of the isolated application of a conditioned signal (CS) was 20 s, the interval between signals was not fixed, varying from 2 min to 4 min. Six to eight combinations of the conditioned and unconditioned stimuli were used for 1 day of the experiment.&#x0D; RESULTS: The increase in the added respiratory resistance was associated with the pronounced reduction of pulmonary and alveolar ventilation, that is, with the hypoventilation type of resistive load realization. Changes in ventilation during the isolated application of a conditioned signal had an alternative character. In particular, as the reinforcement factor increased, a pronounced shift to hyperventilation was noted.&#x0D; CONCLUSION: The reinforcement value of the conditioned reflex changed stepwise, thereby significantly restructuring the proportion between the effectiveness of the adaptive activity in the realization of external resistance to inspiration (the time of stay under a certain load) and its physiological cost (totalities of the deviations of physiological and energy parameters).

Effects of Dynamic Hyperinflation on Left Ventricular Diastolic Function in Healthy Subjects - A Randomized Controlled Crossover Trial.

Objective: Diastolic dysfunction of the left ventricle is common in patients with chronic obstructive pulmonary disease (COPD). Dynamic hyperinflation has been suggested as a key determinant of reduced diastolic function in COPD. We aimed to investigate the effects of induced dynamic hyperinflation on left ventricular diastolic function in healthy subjects to exclude other confounding mechanisms associated with COPD.Design: In this randomized controlled crossover trial (NCT03500822, https://www.clinicaltrials.gov/), we induced dynamic hyperinflation using the validated method of expiratory resistance breathing (ERB), which combines tachypnea with expiratory resistance, and compared the results to those of tachypnea alone. Healthy male subjects (n = 14) were randomly assigned to the ERB or control group with subsequent crossover. Mild, moderate, and severe hyperinflation (i.e., ERB1, ERB2, ERB3) were confirmed by intrinsic positive end-expiratory pressure (PEEPi) using an esophageal balloon catheter. The effects on diastolic function of the left ventricle were measured by transthoracic echocardiographic assessment of the heart rate-adjusted transmitral E/A-ratio and E/e'-ratio.Results: We randomly assigned seven participants to the ERB group and seven to the control group (age 26 [24-26] vs. 24 [24-34], p = 0.81). Severe hyperinflation decreased the E/A-ratio compared to the control condition (1.63 [1.49–1.77] vs. 1.85 [0.95–2.75], p = 0.039), and moderate and severe ERB significantly increased the septal E/e'-ratio. No changes in diastolic function were found during mild hyperinflation. PEEPi levels during ERB were inversely correlated with the E/A ratio (regression coefficient = −0.007, p = 0.001).Conclusions: Our data indicate dynamic hyperinflation as a determinant of left ventricular diastolic dysfunction in healthy subjects. Therapeutic reduction of hyperinflation might be a treatable trait to improve diastolic function in patients with COPD.