Limited Exercise Tolerance Research Articles

Delphi consensus on the American Society of Anesthesiologists’ physical status classification in an Asian tertiary women’s hospital

BackgroundThe American Society of Anesthesiologists (ASA) score is generated based on patients’ clinical status. Accurate ASA classification is essential for the communication of perioperative risks and resource planning. Literature suggests that ASA classification can be automated for consistency and time-efficiency. To develop a rule-based algorithm for automated ASA classification, this study seeks to establish consensus in ASA classification for clinical conditions encountered at a tertiary women’s hospital.MethodsThirty-seven anesthesia providers rated their agreement on a 4-point Likert scale to ASA scores assigned to items via the Delphi technique. After Round 1, the group’s collective responses and individual item scores were shared with participants to improve their responses for Round 2. For each item, the percentage agreement (‘agree’ and ‘strongly agree’ responses combined), median (interquartile range/IQR), and SD were calculated. Consensus for each item was defined as a percentage agreement ≥ 70%, IQR ≤ 1.0, and SD < 1.0.ResultsAll participants completed the study and none had missing data. The number of items that reached consensus increased from 25 (51.0%) to 37 (75.5%) in the second Delphi round, particularly for items assigned ASA scores of III and IV. Nine items, which pertained to alcohol intake, asthma, thyroid disease, limited exercise tolerance, and stable angina, did not reach consensus even after two Delphi rounds.ConclusionsDelphi consensus was attained for 37 of the 49 study items (75.5%), facilitating their incorporation into a rule-based clinical support system designed to automate the prediction of ASA classification.

Long-term follow-up and quality of life in patients receiving extracorporeal membrane oxygenation for pulmonary embolism and cardiogenic shock

BackgroundSince 2019, European guidelines recommend considering extracorporeal life support as salvage strategy for the treatment of acute high-risk pulmonary embolism (PE) with circulatory collapse or cardiac arrest. However, data on long-term survival, quality of life (QoL) and cardiopulmonary function after extracorporeal membrane oxygenation (ECMO) are lacking.MethodsOne hundred and nineteen patients with acute PE and severe cardiogenic shock or in need of mechanical resuscitation (CPR) received venoarterial or venovenous ECMO from 2007 to 2020. Long-term data were obtained from survivors by phone contact and personal interviews. Follow-up included a QoL analysis using the EQ-5D-5L questionnaire, echocardiography, pulmonary function testing and cardiopulmonary exercise testing.ResultsThe majority of patients (n = 80, 67%) were placed on ECMO during or after CPR with returned spontaneous circulation. Overall survival to hospital discharge was 45.4% (54/119). Nine patients died during follow-up. At a median follow-up of 54.5 months (25–73; 56 ± 38 months), 34 patients answered the QoL questionnaire. QoL differed largely and was slightly reduced compared to a German reference population (EQ5D5L index 0.7 ± 0.3 vs. 0.9 ± 0.04; p < 0.01). 25 patients (73.5%) had no mobility limitations, 22 patients (65%) could handle their activities, while anxiety and depression were expressed by 10 patients (29.4%). Return-to-work status was 33.3% (average working hours: 36.2 ± 12.5 h/per week), 15 (45.4%) had retired from work early. 12 patients (35.3%) expressed limited exercise tolerance and dyspnea. 59% (20/34) received echocardiography and pulmonary function testing, 50% (17/34) cardiopulmonary exercise testing. No relevant impairment of right ventricular function and an only slightly reduced mean peak oxygen uptake (76.3% predicted) were noted.ConclusionsSurvivors from severe intractable PE in cardiogenic shock or even under CPR with ECMO seem to recover well with acceptable QoL and only minor cardiopulmonary limitations in the long term. To underline these results, further research with larger study cohorts must be obtained.

The impact of elevated body core temperature on critical power as determined by a 3-min all-out test.

Critical power (CP) delineates the heavy and severe exercise intensity domains, and sustained work rates above CP result in an inexorable progression of oxygen uptake to a maximal value and, subsequently, the limit of exercise tolerance. The finite work capacity above CP, W', is defined by the curvature constant of the power-duration relationship. Heavy or severe exercise in a hot environment generates additional challenges related to the rise in body core temperature (Tc) that may impact CP and W'. The purpose of this study was to determine the effect of elevated Tc on CP and W'. CP and W' were estimated by end-test power (EP; mean of final 30 s) and work above end-test power (WEP), respectively, from 3-min "all-out" tests performed on a cycle ergometer. Volunteers (n = 8, 4 female) performed the 3-min tests during a familiarization visit and two experimental visits (thermoneutral vs. hot, randomized crossover design). Before experimental 3-min tests, the subjects were immersed in water (thermoneutral: 36°C for 30 min; hot: 40.5°C until Tc was ≥38.5°C). Mean Tc was significantly greater in the hot condition than in the thermoneutral condition (38.5 ± 0.0°C vs. 37.4 ± 0.2°C; means ± SD, P < 0.01). All 3-min tests were performed in an environmental chamber [thermoneutral: 18°C, 45% relative humidity (RH); hot: 38 °C, 40% RH]. EP was similar between thermoneutral (239 ± 57 W) and hot (234 ± 66 W; P = 0.55) conditions. WEP was similar between thermoneutral (10.9 ± 3.0 kJ) and hot conditions (9.3 ± 3.6; P = 0.19). These results suggest that elevated Tc has no significant impact on EP or WEP.NEW & NOTEWORTHY The parameters of the power-duration relationship (critical power and W') estimated by a 3-min all-out test were not altered by elevated body core temperature as compared with a thermoneutral condition.

A case of post-COVID-19 mucormycosis with permanent pacemaker posted for functional endoscopic sinus surgery: Anaesthetic challenges.

Sir, The important perioperative challenges during surgical debridement for post-coronavirus disease (COVID)-19 rhino-orbital-cerebral mucormycosis include difficult airway, uncontrolled diabetes mellitus (DM), side effects of amphotericin B (AmB), presence of other comorbidities and post-COVID-19 systemic abnormalities including a decline in respiratory function.[1] We report the successful management of a patient with post-COVID-19 mucormycosis with a permanent pacemaker in situ posted for functional endoscopic sinus surgery (FESS) under general anaesthesia. A 70-year-old male with post-COVID-19 mucormycosis came with complaints of right-sided facial swelling and pain with nasal blockage. The patient when admitted for COVID-19 was given tablets favipiravir and prednisolone and discharged after 15 days. He had a history of syncopal attacks and was diagnosed as having a heart block 8 years back for which a permanent pacemaker had been inserted [Figure 1]. He was a known case of DM and hypertension, with a blood sugar of 490 mg/dL and urine ketones positive on admission, and was started on insulin to control the blood sugar. The airway examination showed Mallampati classification (MPC) grade 3 with a thyromental distance of 6.5 cm. Oedema and pain present on the maxillary and orbital regions limited the mouth opening. A preoperative arterial blood gas (ABG) analysis showed PaO2 60 mmHg, PaCO2 34 mmHg, and pH 7.4 and six-zone involvement on chest radiograph. The baseline oxygen saturation (SpO2) was 91% (room air) and the baseline heart rate was 70/min and regular. The electrocardiogram (ECG) showed ventricular pacing with wide QRS complexes [Figure 2]. The echocardiography showed degenerative changes with fair left ventricular systolic function (ejection fraction of 60%). The pacemaker was identified as VITATRON A20A1SR (mode VVIR) which was reprogrammed to asynchronous V000 mode prior to surgery. The defibrillator, transcutaneous pacing and crash cart trolley were kept ready. After pre-oxygenation, the patient was induced with intravenous fentanyl 50 μg, thiopentone 250 mg and rocuronium and tracheal intubation were facilitated with a C-MAC video laryngoscope. The patient was maintained on oxygen, nitrous oxide, isoflurane and vecuronium. He was extubated at the end of the procedure and shifted to the post-anaesthesia care unit. The pacemaker was programmed to its initial mode after surgery. The COVID-19 mucormycosis patients with a pacemaker in situ pose several challenges for an anaesthesiologist. Diabetic nephropathy, renal toxicity and electrolyte imbalance associated with inj. AmB are major concerns besides preoperative hypokalaemia, fever and hypotension.[2] Perioperative blood pressure, urine output, renal function and serum electrolyte monitoring is mandatory.Figure 1: Chest radiograph showing six zone involvement and a ventricular pacing systemFigure 2: Pacemaker spike precedes each QRS complex with LBBB, discordant ST segment and T waves- consistent with right ventricular pacingSupraglottic oedema, fungal debris in the oropharyngeal region and palatal perforation can lead to difficult mask ventilation and endotracheal intubation.[3] In our patient, the thyromental distance was less, the MPC was grade 3 and the mouth opening was restricted leading to an anticipated difficult airway. Hence, a C-MAC videolaryngoscope was used. Post-COVID-19 pulmonary fibrosis leads to breathlessness, dyspnoea, cough, fatigue, limited exercise tolerance and an abnormal ABG picture (low PaO2, high PaCO2, low SpO2).[4] The patient on preoperative oxygen therapy can desaturate during the laryngoscopy for which adequate pre-oxygenation and minimum time for laryngoscopy and intubation is the key. Hypoxaemia and hypercapnia can increase the pacing threshold, and thus, lead to the failure of the pacemaker to capture. Mucormycosis may exist with diabetic ketoacidosis and further treatment with AmB can lead to renal toxicity, acid-base and electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesemia) and hypovolaemia, which may precipitate arrhythmias. These conditions can cause perioperative interference with the pacemaker function leading to failure to capture and pacemaker dysfunction.[5] In addition, FESS is in proximity to the pacemaker and requires the use of cautery leading to electromagnetic interference.[6] Similarly, the microdebrider can lead to artefacts in the ECG mimicking ventricular tachycardia and even asystole. Hence, we converted the pacemaker to an asynchronous mode; nonetheless, pacemaker failure in the synchronous and asynchronous modes has been noted leading to hypotension, arrhythmias or cardiac arrest. Thus, a post-COVID-19 case of mucormycosis with suboptimal lung function, compromised airway, uncontrolled diabetes and an artificial cardiac pacemaker, posted for FESS was managed successfully with vigilant perioperative monitoring under general anaesthesia. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations

Patients with refractory angina (RA) have poor quality of life and new therapies are needed. XC001 is a novel adenoviral vector expressing multiple isoforms of vascular endothelial growth factor (VEGF) promoting an enhanced local angiogenic effect. The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) trial is a 6-month (with 6-month extension) phase 1/2, first-in-human, multicenter, open-label, single-arm, dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of XC001 in patients with RA. The trial will enroll 33 patients in an initial (n = 12) ascending dose-escalation phase (1×109, 1×1010, 4×1010, and 1×1011 viral particles), followed by phase 2 (n = 21) assessing the highest tolerated dose. Patients must have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy without options for conventional revascularization, demonstrable ischemia on stress testing, and angina limiting exercise tolerance. XC001 will be delivered directly to ischemic myocardium via surgical transthoracic epicardial access. The primary outcome is safety via adverse event monitoring through 6 months. Efficacy assessments include difference from baseline to month 6 in time to 1 mm of ST segment depression, time to angina, and total exercise duration; myocardial blood flow at rest, and stress and coronary flow reserve by positron emission tomography; quality of life; CCS functional class; and angina frequency. The EXACT trial will determine whether direct intramyocardial administration of XC001 in patients with RA is safe and evaluate its effect on exercise tolerance, myocardial perfusion, angina and physical activity, informing future clinical investigation. NCT04125732.

Impact of a submaximal mono-articular exercise on the skeletal muscle function of patients with sickle cell disease.

Sickle cell disease (SCD) patients exhibit a limited exercise tolerance commonly attributed to anaemia, as well as hemorheological and cardio-respiratory abnormalities, but the functional status of skeletal muscle at exercise is unknown. Moreover, the effect of SCD genotype on exercise tolerance and skeletal muscle function has been poorly investigated. The aim of this study was to investigate skeletal muscle function and fatigue during a submaximal exercise in SCD patients. Nineteen healthy individuals (AA), 28 patients with sickle cell anaemia (SS) and 18 with sickle cell-haemoglobin C disease (SC) performed repeated knee extensions exercise (FAT). Maximal isometric torque (Tmax) was measured before and after the FAT to quantify muscle fatigability. Electromyographic activity and oxygenation by near-infrared spectroscopy of the Vastus Lateralis were recorded. FAT caused a reduction in Tmax in SS (-17.0 ± 12.1%, p < 0.001) and SC (-21.5 ± 14.5%, p < 0.05) but not in AA (+ 0.58 ± 29.9%). Root-mean-squared value of EMG signal (RMS) decreased only in SS after FAT, while the median power frequency (MPF) was unchanged in all groups. Oxygenation kinetics were determined in SS and AA and were not different. These results show skeletal muscle dysfunction during exercise in SCD patients, and suggest different fatigue aetiology between SS and SC. The changes in EMG signal and oxygenation kinetics during exercise suggest that the greater skeletal muscle fatigue occurring in SCD patients would be rather due to intramuscular alterations modifications than decreased tissue oxygenation. Moreover, SS patients exhibit greater muscle fatigability than SC.

Extra-motor manifestations in post-polio syndrome (PPS): fatigue, cognitive symptoms and radiological features.

There is a paucity of cerebral neuroimaging studies in post-polio syndrome (PPS), despite the severity of neurological and neuropsychological sequelae associated with the condition. Fatigue, poor concentration, limited exercise tolerance, paraesthesia and progressive weakness are frequently reported, but the radiological underpinnings of these symptoms are poorly characterised. The aim of this study is to evaluate cortical and subcortical alterations in a cohort of adult polio survivors to explore the anatomical substrate of extra-motor manifestations. Thirty-six patients with post-polio syndrome, a disease-control group with amyotrophic lateral sclerosispatients and a cohort of healthy individuals were included in a prospective neuroimaging study with a standardised clinical and radiological protocol. Validated clinical instruments were utilised to assess mood, cognitive and behavioural domains and specific aspects of fatigue. Cortical thickness analyses, subcortical volumetry, brainstem segmentation and region-of-interest(ROI) white matter analyses were undertaken to assess regional grey and white matter alterations. A high proportion of PPS patients exhibited apathy, verbal fluency deficits and reported self-perceived fatigue. On ROI analyses, cortical atrophy was limited to the cingulate gyrus, and the temporal pole and subcortical atrophy were only detected in the left nucleus accumbens. No FA reductions were noted to indicate white matter degeneration in any of the lobes. Despite the high incidence of extra-motor manifestations in PPS, only limited cortical, subcortical and white matter degeneration was identified. Our findings suggest that non-structural causes, such as polypharmacy and poor sleep, may contribute to the complex symptomatology of post-polio syndrome.

Cerebral vs. Cardiovascular Responses to Exercise in Type 2 Diabetic Patients.

The human brain is constantly active and even small limitations to cerebral blood flow (CBF) may be critical for preserving oxygen and substrate supply, e.g., during exercise and hypoxia. Exhaustive exercise evokes a competition for the supply of oxygenated blood between the brain and the working muscles, and inability to increase cardiac output sufficiently during exercise may jeopardize cerebral perfusion of relevance for diabetic patients. The challenge in diabetes care is to optimize metabolic control to slow progression of vascular disease, but likely because of a limited ability to increase cardiac output, these patients perceive aerobic exercise to be more strenuous than healthy subjects and that limits the possibility to apply physical activity as a preventive lifestyle intervention. In this review, we consider the effects of functional activation by exercise on the brain and how it contributes to understanding the control of CBF with the limited exercise tolerance experienced by type 2 diabetic patients. Whether a decline in cerebral oxygenation and thereby reduced neural drive to working muscles plays a role for “central” fatigue during exhaustive exercise is addressed in relation to brain’s attenuated vascular response to exercise in type 2 diabetic subjects.

Treatment with brain-derived neurotrophic factor for skeletal muscle abnormalities in heart failure

Exercise tolerance is limited in patients with heart failure (HF), and the limited exercise tolerance is an independent determinant of poor prognosis. It is known that skeletal muscle abnormalities are important factors for limited exercise tolerance. The cause of skeletal muscle abnormalities in HF is unclear.

Effect of Blood Flow on Hemoglobin and Myoglobin Oxygenation in Contracting Muscle Using Near-Infrared Spectroscopy.

Insufficient O2 delivery to, and uptake by skeletal muscle can produce mobility limitations for patients with chronic diseases. Near-infrared spectroscopy (NIRS) can be used to noninvasively quantify the balance between skeletal muscle O2 delivery and utilization during contraction. However, it is not clear how the oxygenated or deoxygenated NIRS signal should be used to assess muscle O2 changes. This issue is related to the fact that the contributions of hemoglobin (Hb) and myoglobin (Mb) cannot be distinguished. This conundrum can be resolved by quantitative analysis of experimental data by computer simulations with a mechanistic, mathematical model. Model simulations distinguish dynamic responses of the oxygenated (HbO2, MbO2) and deoxygenated (HHb, HMb) contributions to the NIRS signal components (HbMbO2, HHbMb). Simulations of muscle O2 uptake and NIRS kinetics correspond closely to published experimental data (Hernández et al.,J Appl Physiol 108: 1169-1176, 2010). Simulated muscle O2 uptake and oxygenation kinetics with different blood flows indicate (1) faster O2 delivery is responsible for slower muscle oxygenation kinetics; (2) Hb and Mb contributions to the HbMbO2 are similar (40-60%); and (3) Hb and Mb contributions to the HHbMb are significantly different, 80% and 20%, respectively. The effect of slow blood flow kinetics on oxygenated Hb and Mb contributions is minimal. However, the effect on the imbalance between O2 delivery and utilization rates causes significant overshoots and undershoots of deoxygenated Hb and Mb contributions. Model analysis in combination with NIRS measurements and information on hemodynamic and microvascular distribution can help to determine the use of NIRS signal in evaluating the factors limiting exercise tolerance in health and disease states.

Influence of exertional hypoxemia on cerebral oxygenation in fibrotic interstitial lung disease

It is unknown whether hypoxemia, a hallmark of fibrotic interstitial lung disease (f-ILD), may impair cerebral oxygenation during exercise in these patients.Twenty-seven patients [23 males, 72 ± 8 years, lung diffusing capacity for carbon monoxide (DLCO) = 44 ± 11 % predicted] and 12 controls performed an incremental bicycle test. Prefrontal oxygenation [tissue saturation index (TSI)] was assessed by near-infrared spectroscopy.Patients showed lower arterial O2 saturation (SpO2) and larger fall in cerebral TSI during exercise vs controls (p < 0.05). However, changes (Δ) from rest to peak-exercise in SpO2 (-2.2 % to -26.9 %) and TSI (1.4 % to -16.6 %) varied substantially among patients. In the 16 patients showing significant cerebral deoxygenation (Δ TSI ≥ 4% based on controls), SpO2 decreased more (-12.6 ± 6.7 % vs -5.7 ± 2.8 %, p = 0.001) and peak O2 uptake was lower (68.3 ± 19.2 % vs 87.8 ± 24.8 % predicted, p = 0.03) vs their 11 counterparts. In association with DLCO and forced vital capacity, Δ cerebral TSI independently predicted peak O2 uptake on multivariable regression analysis (R2 = 0.54).Exertional hypoxemia impairs cerebral oxygenation in a dose-dependent fashion in f-ILD. Future studies are warranted to investigate whether this potentially reversible abnormality play a contributory role in limiting exercise tolerance in these patients.

Ascorbate attenuates cycling exercise-induced neuromuscular fatigue but fails to improve exertional dyspnea and exercise tolerance in COPD.

We examined the effect of intravenous ascorbate (VitC) administration on exercise-induced redox balance, inflammation, exertional dyspnea, neuromuscular fatigue, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Eight COPD patients completed constant-load cycling (∼80% of peak power output, 83 ± 10 W) to task failure after intravenous VitC (2 g) or saline (placebo, PL) infusion. All participants repeated the shorter of the two exercise trials (isotime) with the other infusate. Quadriceps fatigue was determined by pre- to postexercise changes in quadriceps twitch torque (ΔQtw, electrical femoral nerve stimulation). Corticospinal excitability before, during, and after exercise was assessed by changes in motor evoked potentials triggered by transcranial magnetic stimulation. VitC increased superoxide dismutase (marker for endogenous antioxidant capacity) by 129% and mitigated C-reactive protein (marker for inflammation) in the plasma during exercise but failed to alter the exercise-induced increase in lipid peroxidation (malondialdehyde) and free radicals [electron paramagnetic resonance (EPR)-spectroscopy]. Although VitC did, indeed, decrease neuromuscular fatigue (ΔQtw: PL -29 ± 5%, VitC -23 ± 6%, P < 0.05), there was no impact on corticospinal excitability and time to task failure (∼8 min, P = 0.8). Interestingly, in terms of pulmonary limitations to exercise, VitC had no effect on perceived exertional dyspnea (∼8.5/10) and its determinants, including oxygen saturation ([Formula: see text]) (∼92%) and respiratory muscle work (∼650 cmH2O·s·min-1) (P > 0.3). Thus, although VitC facilitated indicators for antioxidant capacity, diminished inflammatory markers, and improved neuromuscular fatigue resistance, it failed to improve exertional dyspnea and cycling exercise tolerance in patients with COPD. As dyspnea is recognized to limit exercise tolerance in COPD, the otherwise beneficial effects of VitC may have been impacted by this unaltered sensation.NEW & NOTEWORTHY We investigated the effect of intravenous vitamin C on redox balance, exertional dyspnea, neuromuscular fatigue, and exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. Acute vitamin C administration increased superoxide dismutase (marker of antioxidant capacity) and attenuated fatigue development but failed to improve exertional dyspnea and exercise tolerance. These findings suggest that a compromised redox balance plays a critical role in the development of fatigue in COPD but also highlight the significance of exertional dyspnea as an important symptom limiting the patients' exercise tolerance.

Heart rate response during cardiopulmonary exercise in heart transplant recipients

Abstract Background Denervation at heart transplant (HTx) results in attenuated heart rate (HR) control and limited exercise tolerance. Purpose The aim of this study was to assess longitudinal changes in the HR response to exercise in HTx recipients. We compared the results with those of healthy controls. Methods Seventy-four HTx recipients were enrolled in a cardiopulmonary exercise trial. The HR response to maximal exercise was tested at 11 weeks and at 1- and 3-years follow-up post HTx, and compared with the HR response in 50 age and gender matched controls. The HR was measured at rest, at 25-, 50-, 75-, and 100% of VO2peak, and 30 sec, 1, 2, and 4 min after peak exercise on a treadmill or bicycle ergometer. We also assessed the HR reserve and the chronotropic response index (CRI). Results Elleven weeks after HTx, the HR response to exercise was blunted, but improved significantly during follow-up. The change in HR from rest to peak exercise increased by 53% (41 bpm vs 62 bpm; p&amp;lt;0.001) from inclusion to 12 months follow-up, but levelled off between 12- and 36 months (62 bpm vs 65 bpm; p=0.59) (Figure 1). In comparison, the exercise-induced increase in HR in healthy controls was 117 bpm. In HTx recipients, approximately 40% of the total increase in HR occurred between rest and 25% of VO2peak at inclusion (Figure). In contrast, only 31% of the increase in HR in healthy controls occurred between rest and 25% of VO2peak (p&amp;lt;0.001). The fall in HR during the first 4 minutes after exercise increased over the duration of the study (p&amp;lt;0.001 for all comparisons between inclusion and 12 months, and 12- and 36 months at 30 sec, 1, 2, 3 and 4 min after exercise). During the first minute after the end of exercise, the HR rose 2 bpm at baseline, but fell 10 bpm at 12 months (p for difference &amp;lt;0.001). However, even at 36 months, the decline in HR after exercise remained less rapid than in healthy controls (p&amp;lt;0.001) (Figure). CRI increased between baseline and 12 months, but levelled off between the 12-month visit and 36 months (0.50±0.2 vs 0.79±0.3; p&amp;lt;0.001 and 0.79±0.3 vs 0.81±0.3; p=0.51). The chronotropic response was normalized (&amp;gt;0.85) in 44% of the HTx recipients at 1 year and in 51% at 3 year after HTx. Conclusion The increase and decrease in HR during exercise are considerably muted in de novo HTx recipients. The HR response improves during the first year after surgery, and thereafter levels off. In contrast the decline in HR after exercise seems to increase with time, which may be related to the effect of exercise. This suggests that partial re-innervation takes place. Whether this response continues to improve in the longer term remains to be determined. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority

Acute respiratory muscle unloading improves time-to-exhaustion during moderate- and heavy-intensity cycling in obese adolescent males

Obesity significantly impairs breathing during exercise. The aim was to determine, in male obese adolescents (OB), the effects of acute respiratory muscle unloading, obtained by switching the inspired gas from ambient air (AIR) to a normoxic helium + oxygen gas mixture (HeO2) (AIR → HeO2) during moderate [below gas exchange threshold (GET)] and heavy [above GET] constant work rate cycling. Ten OB [age 16.0 ± 2.0 years (mean ± SD); body mass index (BMI) 38.9 ± 6.1 kg/m2] and ten normal-weight age-matched controls (CTRL) inspired AIR for the entire exercise task, or underwent AIR → HeO2 when they were approaching volitional exhaustion. In OB time to exhaustion (TTE) significantly increased in AIR → HeO2 vs. AIR during moderate [1524 ± 480 s vs. 1308 ± 408 (P = 0.024)] and during heavy [570 ± 306 s vs. 408 ± 150 (P = 0.0154)] exercise. During moderate exercise all CTRL completed the 40-min task. During heavy exercise no significant differences were observed in CTRL for TTE (582 ± 348 s [AIR → HeO2] vs. 588 ± 252 [AIR]). In OB, but not in CTRL, acute unloading of respiratory muscles increased TTE during both moderate- and heavy-exercise. In OB, but not in CTRL, respiratory factors limit exercise tolerance during both moderate and heavy exercise.

Influence of blood flow occlusion on muscular recruitment and fatigue during maximal-effort small muscle-mass exercise.

The heavy-to-severe intensity exercise threshold (i.e. critical force) distinguishes between steady-state and progressive metabolic and neuromuscular responses to exercise. High levels of skeletal muscle sensory feedback related to peripheral fatigue development are thought to restrict motor unit activation and limit exercise tolerance. Utilizing limb blood flow occlusion, we demonstrate that critical force reflects an oxygen-delivery-dependent balance between motor unit activation and peripheral fatigue development. Our findings suggest that mechanisms which determine the total force-producing capacity of exercising skeletal muscle are significantly altered during blood flow occlusion. These findings may have widespread implications for exercise tolerance in patient populations who experience partial vascular occlusion or altered neuromuscular reflexes. High levels of muscle sensory feedback restrict motor unit activation and limit exercise tolerance. The roles of muscle fatigue development and motor unit activation in determining the heavy- to severe-intensity threshold (critical force; CF) remain unclear. This study utilized blood flow occlusion (OCC) to determine relationships between muscle fatigue development and motor unit activation during the determination of CF. We hypothesized that (1) OCC would exacerbate peripheral fatigue development and increase the rate of motor unit deactivation, and (2) blood flow reperfusion (REP) would result in muscle recovery and re-recruitment of motor units despite continuous maximal effort, (3) resulting in an end-exercise force not different from CF. Seven young, healthy subjects performed maximal-effort rhythmic handgrip exercise for 5min under control conditions (CON) and during OCC and REP. Peripheral fatigue development and motor unit activation were measured via electrical stimulation and electromyography, respectively, during each test. OCC resulted in significantly greater peripheral fatigue development than CON (54.3±34.8%;P<0.001). Motor unit deactivation was only observed during OCC (P<0.001). REP resulted in significant peripheral recovery (P<0.001) and the re-recruitment of motor units (P<0.001) to levels not different from CON. While OCC resulted in a significantly greater reduction in force production compared to CON (65.7±35.6%;P<0.001), REP resulted in the restoration of maximal-effort force production (266±19N;P<0.001) to levels not different from CF (276±55N).These data suggest that CF reflects an oxygen-delivery-dependent balance between motor unit activation and peripheral fatigue development. Furthermore, this study established that mechanisms which determine the total force-producing capacity of exercising skeletal muscle are altered during OCC.

Contrasting Patterns Of Respiratory And Locomotor Muscle Deoxygenation And Total Hemoglobin During Incremental Ramp Cycling

Respiratory muscle demands during severe intensity exercise may constrain the blood flow increase to locomotory muscles, thereby limiting exercise tolerance. Muscle mitochondrial O2 delivery depends on both perfusive and diffusive O2 transport, the former reflecting the O2 delivery-utilization balance and the latter exercise-induced changes in muscle total hemoglobin (THb). Resolution of changes in deoxygenation and THb simultaneously within these two muscle groups will provide novel insights into vascular and metabolic control. PURPOSE: We investigated absolute deoxygenated [Hb+Mb] (HHb, index of fractional O2 extraction) and THb responses in respiratory and locomotor muscle using time-resolved near-infrared spectroscopy (TR-NIRS). METHODS: Ten males performed ramp incremental cycling (20 W·min-1) to exhaustion while measuring pulmonary VO2, HHb and THb (9-10th intercostal space for intercostal muscle and diaphragm, IC-DP, and vastus lateralis, VL). HHb and THb were corrected for adipose tissue thickness (ATT) at each optode site, using the THb-ATT regression. RESULTS: HHb increased systematically with power output (PO) in VL and plateaued above ~80% POmax (Figure 1A). In contrast, HHb in IC-DP was unchanged from rest. THb in VL increased modestly and plateaued above ~50% POmax, whereas THb in IC-DP declined gently from rest such that THb was greater in VL than IC-DP from 30 to 100 % POmax (Figure 1B). CONCLUSIONS: These disparate HHb and THb profiles imply a muscle-specific regulation of perfusive and diffusive O2 fluxes for respiratory versus locomotory muscle(s). Supported by JSPS-17J09854, 18K17875

Are the "critical" inspiratory constraints actually decisive to limit exercise tolerance in COPD?

The concept of critical inspiratory constraints is key to the modern understanding of exercise pathophysiology in patients with moderate-to-severe COPD https://bit.ly/2A6bCxD

COVID-19 Pandemic Acute Respiratory Distress Syndrome Survivors: Pain After the Storm?

COVID-19 Pandemic Acute Respiratory Distress Syndrome Survivors: Pain After the Storm?

Bronchiectasis in Primary Antibody Deficiencies: A Multidisciplinary Approach.

Bronchiectasis, the presence of bronchial wall thickening with airway dilatation, is a particularly challenging complication of primary antibody deficiencies. While susceptibility to infections may be the primary factor leading to the development of bronchiectasis in these patients, the condition may develop in the absence of known infections. Once bronchiectasis is present, the lungs are subject to a progressive cycle involving both infectious and non-infectious factors. If bronchiectasis is not identified or not managed appropriately, the cycle proceeds unchecked and yields advanced and permanent lung damage. Severe symptoms may limit exercise tolerance, require frequent hospitalizations, profoundly impair quality of life (QOL), and lead to early death. This review article focuses on the appropriate identification and management of bronchiectasis in patients with primary antibody deficiencies. The underlying immune deficiency and the bronchiectasis need to be treated from combined immunology and pulmonary perspectives, reflected in this review by experts from both fields. An aggressive multidisciplinary approach may reduce exacerbations and slow the progression of permanent lung damage.

Heart Rate Response after Heart Transplantation

Denervation after heart transplantation (HTx) results in attenuated heart rate (HR) control and limited exercise tolerance. The aim of this study was to assess HR response changes to exercise with time in HTx recipients, compared with healthy controls. The HR response to maximal cardiopulmonary exercise was tested in 50 de novo HTx recipients at 11 weeks (range 7-16) after surgery, at 1-year follow-up and in 50 age and gender matched controls. The HR was measured at rest, at 25-, 50-, 75-, and 100% of VO2peak, and 30 sec, 1, 2, and 4 min after peak exercise on a treadmill or bicycle ergometer. We also assessed the HR reserve and the chronotropic response index. 11 weeks after HTx, the HR response to exercise was blunted, but improved significantly during follow-up. The change in HR from rest to peak exercise increased by 32% (46 bpm vs 68 bpm; p&lt0.001) from inclusion to the 12 months' follow-up (Figure). In comparison, the change in HR during exercise in controls was 115 bpm. In HTx recipients, approximately 50 % of the total increase in HR occurred between rest and 25% of VO2peak (figure). In the controls, roughly 40% of the total increase in HR occurred during the initial 25% of VO2peak. The HTx recipients had a significantly higher change in HR between 75- and 100% of VO2peak at inclusion than at 1-year follow-up (p=0.004) and this delayed change in HR was higher than in controls (p = 0.001). The chronotropic response index increased during follow-up (0.48 ± 0.2 vs 0.79 ± 0.2; p&lt0.001) and normalized in 50% of the HTx recipients at 1 year. Finally, the HR declined more rapidly after exercise at follow-up than at inclusion, however, the decline remained slower than in controls (Figure). The increase and decrease in heart rate during exercise are considerably reduced in de novo HTx recipients, but improve during the first year after surgery. Whether this response continues to improve during longer follow-up remains to be determined.