Substrate-induced strain in molybdenum disulfide grown by aerosol-assisted chemical vapor deposition.

Transition metal dichalcogenides have been extensively studied in recent years because of their fascinating optical, electrical, and catalytic properties. However, low-cost, scalable production remains a challenge. Aerosol-assisted chemical vapor deposition (AACVD) provides a new method for scalable thin film growth. In this study, we demonstrate the growth of molybdenum disulfide (MoS2) thin films using AACVD method. This method proves its suitability for low-temperature growth of MoS2thin films on various substrates, such as glass, silicon dioxide, quartz, silicon, hexagonal boron nitride, and highly ordered pyrolytic graphite. The as-grown MoS2shows evidence of substrate-induced strain. The type of strain and the morphology of the as-grown MoS2highly depend on the growth substrate's surface roughness, crystallinity, and chemical reactivity. Moreover, the as-grown MoS2shows the presence of both direct and indirect band gaps, suitable for exploitation in future electronics and optoelectronics.

Effect of experimental modulation of mood on exertional dyspnoea in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Dyspnoea is a debilitating symptom in individuals with chronic obstructive pulmonary disease (COPD) and a range of other chronic cardiopulmonary diseases and is often associated with anxiety and depression. The present study examined the effect of visually-induced mood shifts on exertional dyspnoea in individuals with COPD. METHODS: Following familiarization, 20 participants with mild to severe COPD (age 57-79 years) attended three experimental sessions on separate days, performing two 5-min treadmill exercise tests separated by a 30-min interval on each day. During each exercise test, participants viewed either a positive, negative or neutral set of images sourced from the International Affective Picture System (IAPS) and rated dyspnoea or leg fatigue (0-10). Heart rate (HR) and peripheral oxygen saturation (SpO2 ) were measured at 1-min intervals during each test. Mood valence ratings were obtained using Self-Assessment Manikin (SAM) scale (1-9). RESULTS: Mood valence ratings were significantly higher when viewing positive (end-exercise mean ± SEM = 7.6 ± 0.3) compared to negative IAPS images (2.4 ± 0.3, p < 0.001). Dyspnoea intensity (mean ± SEM = 5.8 ± 0.4) and dyspnoea unpleasantness (5.6 ± 0.3) when viewing negative images were significantly higher compared to positive images (4.2 ± 0.4, p = 0.004 and 3.4 ± 0.5, p = 0.003). Eighty-five percent of participants (n = 17) met the minimal clinically important difference (MCID) criteria for both dyspnoea intensity and unpleasantness. HR, SpO2 and leg fatigue did not differ significantly between conditions. CONCLUSION: These findings indicate that the negative affective state worsens dyspnoea in COPD, thereby suggesting strategies aimed at reducing the likelihood of negative mood or improving the mood may be effective in managing morbidity associated with dyspnoea in COPD.

Experimental modulation of mood by acoustic stimulation and its effect on exertional dyspnoea.

We examined the interactions between acoustically driven mood modulation and dyspnoea. Following familiarisation, 18 healthy participants attended three experimental sessions on separate days performing two 5 min treadmill tests with a 30 min interval per session while listening to either a positive, negative or neutral set of standardised International Affective Digitised Sounds (IADS). Participants rated intensity and affective domains of dyspnoea during the first exercise test and mood during the second. Mood valence was significantly higher when listening to positive (mean (95% CI): 6.5 (5.9-7.2)) compared with negative sounds (3.6 (2.9-4.4); p<0.001). Dyspnoea intensity and affect were statistically significantly lower when listening to positive (2.4 (1.8-2.9) and 1.3 (0.7-1.9)) compared with negative IADS (3.2 (2.3-3.7), p=0.013 and 2.3 (1.3-3.3), p=0.009). These findings indicate that acoustically induced mood changes influence exertional dyspnoea.

Exercise training in COPD: What is it about intensity?

Most of the current guidelines for pulmonary rehabilitation recommend higher, over lower, intensity exercise training for COPD. Typically, we consider intensity of exercise training to be a key component of any exercise training programme. Whilst studies of young individuals have demonstrated that higher exercise training intensity results in greater improvements in exercise capacity, the evidence for older patients is not so clear cut. In COPD, there is limited evidence regarding the optimal intensity of exercise training. Using both physiological (peak exercise capacity) and patient-centred (e.g. quality of life) outcomes, it remains inconclusive if higher intensity exercise training bestows any greater benefit than low-intensity exercise. If we examine the data from interval training studies, which used both high- and low-intensity interval and continuous exercise, we are able to generate more data for comparison. Unfortunately, these data are challenging to interpret due to heterogeneity in how interval training was prescribed. However, when we normalize the interval training data for training volume and examine the change in peak cycling power, there is a relationship between training intensity and increase in peak power (Wpeak , r = 0.68, P < 0.05). Hence, whilst there is an inconclusive amount of evidence to support this intervention based on studies that only examined high- versus low-intensity continuous exercise, the additional data from interval training studies would suggest that higher intensity may be superior in terms of increases in Wpeak . Future studies should focus on establishing a threshold and an optimal training intensity for COPD.

An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea.

BACKGROUND: Dyspnea is a common, distressing symptom of cardiopulmonary and neuromuscular diseases. Since the ATS published a consensus statement on dyspnea in 1999, there has been enormous growth in knowledge about the neurophysiology of dyspnea and increasing interest in dyspnea as a patient-reported outcome. PURPOSE: The purpose of this document is to update the 1999 ATS Consensus Statement on dyspnea. METHODS: An interdisciplinary committee of experts representing ATS assemblies on Nursing, Clinical Problems, Sleep and Respiratory Neurobiology, Pulmonary Rehabilitation, and Behavioral Science determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant expertise. The final content of this statement was agreed upon by all members. RESULTS: Progress has been made in clarifying mechanisms underlying several qualitatively and mechanistically distinct breathing sensations. Brain imaging studies have consistently shown dyspnea stimuli to be correlated with activation of cortico-limbic areas involved with interoception and nociception. Endogenous and exogenous opioids may modulate perception of dyspnea. Instruments for measuring dyspnea are often poorly characterized; a framework is proposed for more consistent identification of measurement domains. CONCLUSIONS: Progress in treatment of dyspnea has not matched progress in elucidating underlying mechanisms. There is a critical need for interdisciplinary translational research to connect dyspnea mechanisms with clinical treatment and to validate dyspnea measures as patient-reported outcomes for clinical trials.

Exertional dyspnea responses to the Dyspnea Challenge in heart failure: Comparison to chronic obstructive pulmonary disease.

BACKGROUND: In heart failure (HF), exertional dyspnea is a common symptom, but validated field-based tests for its measurement are limited. The Dyspnea Challenge is a two-minute uphill treadmill walk designed to measure exertional dyspnea in cardiopulmonary disease. OBJECTIVES: The purpose of this study was to establish the test-retest reliability of the Dyspnea Challenge in HF and to compare the exercise responses to a group with chronic obstructive pulmonary disease (COPD). METHODS: The study was an experimental, single-blind, randomized, multi-site project that recruited individuals with HF (New York Heart Association I-III) and COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV). Participants completed two visits. On the first visit, participants performed two six-minute walk tests (6MWT), followed by two to three Dyspnea Challenges to calculate treadmill speed and gradient. At Visit Two, participants performed two separate Dyspnea Challenges, with one including measures of pulmonary gas exchange and central hemodynamics. RESULTS: Twenty-one individuals with HF (10 female; 66±11years; ejection fraction:45.3 ± 6.1%; six-minute distance(6MWD) 520 ± 97 m), and 25 COPD (11 female; 68 ± 10 yr; forced expiratory volume in 1 s:47.6 ± 11.5%; 6MWD: 430 ± 101 m). Intraclass correlation coefficients demonstrated excellent test-retest reliability for HF (0.94, P<.01) and COPD (0.95, P<.01). While achieving similar end-exercise exertional dyspnea intensities (P=.60), the HF group walked at a higher average speed (4.2 ± 0.8 vs. 3.5 ± 0.8km·h-1) and gradient (10.3 ± 2.8 vs. 9.6 ± 2.8%) and a greater oxygen uptake (P<.01) and ventilation (P<.01) than those with COPD. While achieving similar cardiac outputs (P=.98), stroke volumes (P=.97), and heart rates (P=.83), those with HF displayed a larger arteriovenous oxygen difference (P<.01), while those with COPD exhibited greater decreases in inspiratory capacity (P=.03), arterial oxygen saturation (P=.02), and breathing reserve (P<.01). CONCLUSIONS: The Dyspnea Challenge is a reliable test-retest measure of exertional dyspnea in HF. Typical to their pathologies, HF seemed limited by an inadequate modulation of cardiac output, while ventilatory constraints hampered those with COPD.

Fixed-intensity exercise tests to measure exertional dyspnoea in chronic heart and lung populations: a systematic review.

INTRODUCTION: Exertional dyspnoea is the primary diagnostic symptom for chronic cardiopulmonary disease populations. Whilst a number of exercise tests are used, there remains no gold standard clinical measure of exertional dyspnoea. The aim of this review was to comprehensively describe and evaluate all types of fixed-intensity exercise tests used to assess exertional dyspnoea in chronic cardiopulmonary populations and, where possible, report the reliability and responsiveness of the tests. METHODS: A systematic search of five electronic databases identified papers that examined 1) fixed-intensity exercise tests and measured exertional dyspnoea, 2) chronic cardiopulmonary populations, 3) exertional dyspnoea reported at isotime or upon completion of fixed-duration exercise tests, and 4) published in English. RESULTS: Searches identified 8785 papers. 123 papers were included, covering exercise tests using a variety of fixed-intensity protocols. Three modes were identified, as follows: 1) cycling (n=87), 2) walking (n=31) and 3) other (step test (n=8) and arm exercise (n=2)). Most studies (98%) were performed on chronic respiratory disease patients. Nearly all studies (88%) used an incremental exercise test. 34% of studies used a fixed duration for the exercise test, with the remaining 66% using an exhaustion protocol recording exertional dyspnoea at isotime. Exertional dyspnoea was measured using the Borg scale (89%). 7% of studies reported reliability. Most studies (72%) examined the change in exertional dyspnoea in response to different interventions. CONCLUSION: Considerable methodological variety of fixed-intensity exercise tests exists to assess exertional dyspnoea and most test protocols require incremental exercise tests. There does not appear to be a simple, universal test for measuring exertional dyspnoea in the clinical setting.

Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response.

RATIONALE: Opioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely. OBJECTIVES: Evaluate the effect of morphine on dyspnea and ventilatory drive under well-controlled laboratory conditions. METHODS: Six healthy volunteers received morphine (0.07 mg/kg) and placebo intravenously on separate days (randomized, blinded). We measured two responses to a CO(2) stimulus: (1) perceptual response (breathing discomfort; described by subjects as "air hunger") induced by increasing partial pressure of end-tidal carbon dioxide (Pet(CO2)) during restricted ventilation, measured with a visual analog scale (range, "neutral" to "intolerable"); and (2) ventilatory response, measured in separate trials during unrestricted breathing. MEASUREMENTS AND MAIN RESULTS: We determined the Pet(CO2) that produced a 60% breathing discomfort rating in each subject before morphine (median, 8.5 mm Hg above resting Pet(CO2)). At the same Pet(CO2) after morphine administration, median breathing discomfort was reduced by 65% of its pretreatment value; P < 0.001. Ventilation fell 28% at the same Pet(CO2); P < 0.01. The effect of morphine on breathing discomfort was not significantly correlated with the effect on ventilatory response. Placebo had no effect. CONCLUSIONS: (1) A moderate morphine dose produced substantial relief of laboratory dyspnea, with a smaller reduction of ventilation. (2) In contrast to an earlier laboratory model of breathing effort, this laboratory model of air hunger established a highly significant treatment effect consistent in magnitude with clinical studies of opioids. Laboratory studies require fewer subjects and enable physiological measurements that are difficult to make in a clinical setting. Within-subject comparison of the response to carefully controlled laboratory stimuli can be an efficient means to optimize treatments before clinical trials.

Optimising the Dyspnoea Challenge: exertional dyspnoea responses to changing treadmill gradients.

BACKGROUND: The Dyspnoea Challenge is a two-minute treadmill walk designed to measure exertional dyspnoea(ED). To efficiently individualise workload, we aimed to assess; 1) whether the Dyspnoea Challenge is responsive to 1% changes in treadmill gradient and 2) the minimum gradient variation necessary to generate a clinically meaningful change in ED (≥1 modified Borg scale). METHODS: Thirty individuals with COPD(GOLD II-IV) (age: 69.2 ± 9.2 years; FEV1: 49.3 ± 19.1%) completed six Dyspnoea Challenges at a fixed treadmill speed of 3 km·h-1 and at a gradient of between 3% and 8%, performed in random order. ED intensity and leg fatigue were measured using the 0-10 modified Borg scale. Heart rate(HR) and oxygen saturation(SpO2) were monitored continuously. A multidimensional dyspnoea profile(MDP) was used to quantify the discomfort, physical, e.g., work/effort and breathing frequency, and emotional components of ED. RESULTS: Higher treadmill gradients generated stronger intensities of ED (3%:2.6 ± 1.8; 4%:2.8 ± 2.2; 5%:3.2 ± 2.2; 6%:3.4 ± 2.2; 7%:3.7 ± 1.8; 8%:4.0 ± 2.1units). Statistical changes were observed in ED(e.g.,3 vs. 5%: P = .03) and the MDP discomfort data(e.g.,4 vs. 6%: P = .04) at ≥ a 2% variation in treadmill gradient. Linear regression found a 4% variation in treadmill gradient corresponded to a rise in ED ≥ 1unit. Increases in ED intensity corresponded to heightened sensations of work/effort(P < .01) and breathing frequency(P < .01). There were no changes in emotional constructs(P = .27). While there was an increase in HR with increasing gradient(P < .01), no differences were observed in end-exercise SpO2(P = .79) or leg fatigue(P = .06). CONCLUSION: To significantly change ED, the treadmill gradient must be manipulated by ≥ 2%, with a ≥ 4% change in gradient required to induce a clinically meaningful change in ED.

Exertional Dyspnoea responses reported in the Dyspnoea Challenge and measures of disease severity in COPD.

BACKGROUND: The Dyspnoea Challenge has been developed to facilitate the field-based measure of exertional dyspnoea(ED). To further validate the test, we aimed to; investigate the relationship between end-exercise ED, generated by a fixed-intensity Dyspnoea Challenge(DCFIX), and measures of disease severity (Forced expiratory volume in 1 s(FEV1), six-minute walk distance(6MWD), breathing reserve(V̇E/MVV), modified medical research council dyspnoea scale (mMRC), Body-mass index, airflow Obstruction, Dyspnoea, and Exercise (BODE index) and compare the physiological response of the DCFIX to a six-minute walk test(6MWT). METHODS: Thirty-two individuals (15 female) with COPD (GOLD II-IV) (age: 69.7 ± 9.4 yrs; FEV1: 49.1 ± 18.2 %) performed 2×6MWT and 2xDCFIX at a treadmill speed of 3 km h-1 and gradient of 4 %. The intensity of ED was measured using the modified Borg dyspnoea scale at baseline and end-exercise with heart rate (HR) and oxygen saturation (SpO2) monitored continuously. During 1×6MWT and 1xDCFIX pulmonary gas exchange, cardiac output (Q̇) and dynamic hyperinflation were measured. RESULTS: End-exercise ED measured during the DCFIX was not correlated to FEV1, but moderately correlated to; 6MWD(rs = -0.54, P < .01), V̇E/MVV (rs = 0.46, P = .02), mMRC(rs = 0.45, P = .01), and the BODE index(rs = 0.53, P < .01). When comparing the DCFIX and 6MWT, participants walked to comparable levels of oxygen consumption(P = .38), ventilation(P = .37), Q̇(P = .20), V̇E/MVV(P = .83), maximum HR percentages(P = .67) and dynamically hyperinflated to a similar degree(P = .37). CONCLUSIONS: The Dyspnoea Challenge is correlated to different parameters of disease severity and produces a similar physiological and ED response to that of the 6MWT with the added benefit of being appropriate for longitudinal assessment of ED.

Examining the repeatability of a novel test to measure exertional dyspnoea in chronic obstructive pulmonary disease.

BACKGROUND: Exertional dyspnoea(ED) is a hallmark of chronic obstructive pulmonary disease(COPD). We examined the repeatability and face validity of the end-exercise ED(EDend) response during the Dyspnoea Challenge and compared those to the six-minute walk test (6MWT) in COPD. METHODS: Twenty-six individuals with COPD(13 Females, age:69 ± 5.5yrs, FEV1:63.4 ± 11.9 %) completed 2 × 6MWTs and 4 x Dyspnoea Challenges on three occasions. The challenge consisted of a two-minute treadmill walk at 80 % of 6MWT speed(3.9 ± 0.5 km·hr-1) at either a low(LIDC:5.3 ± 2%) or high angle of incline(HIDC:9.5 ± 3%). Dyspnoea(0-10 scale), heart rate(HR) and oxygen saturation(SpO2) were monitored continuously. RESULTS: Mean 6MWT distance was 488 ± 58 m. End-exercise ED and HR were higher in the HIDC(EDend 6.2 ± 2.0; HR: 123 ± 17beats·min-1) compared to the LIDC(EDend 4.2 ± 2.0; HR: 119 ± 15beats·min-1) and the 6MWT(EDend 4.3 ± 2.0; HR: 115 ± 16beats·min-1)(P < 0.01). SpO2 was not different between 6MWT, LIDC or HIDC(P = 0.34). The intraclass correlation coefficient(ICC) for each intensity was excellent (HIDC, ICC = 0.88, LIDC, ICC = 0.93, P < 0.001) with neither reporting bias(HIDC, P = 0.63; LIDC, P = 0.94). CONCLUSIONS: The Dyspnoea Challenge is a simple measure of ED that appears to have both repeatability and face validity. With further optimisation, this test may enhance the field-based clinical assessment of ED.

Repeated six-minute walk tests for outcome measurement and exercise prescription in outpatient cardiac rehabilitation: a longitudinal study.

OBJECTIVE: To determine whether repeated 6-minute walk tests (6MWTs) are required for outcome measurement and exercise prescription in a typical cardiac rehabilitation (CR) population. DESIGN: Prospective longitudinal observational study. SETTING: Outpatient community health center. PARTICIPANTS: Sixty-one of 154 consecutive patients. INTERVENTION: 6MWTs (N = 2) were conducted at 3 assessment points: at CR start, postcompletion, and 6-months postcompletion. MAIN OUTCOME MEASURE: 6MWT distance (6MWD). RESULTS: Mean 6MWD for the first (6MWT1) and second (6MWT2) 6MWTs at the 3 assessment points were 507 ± 85 (522 ± 84), 532 ± 86 (560 ± 87), and 549 ± 99 (575 ± 107)m. Repeated 6MWDs strongly correlated at each assessment point, with intraclass correlation coefficients of .96 (95% confidence interval [CI], 0.93-.98), .97 (95% CI, .92-.98), and .94 (95% CI, .89-.97), respectively. Relative increases in mean 6MWD from 6MWT1 to 6MWT2 at each assessment point were 3%, 5%, and 5%, respectively (P<.001 in each case). Differences in walking speed derived from 6MWD1 and 6MWD2 did not translate into differences in exercise prescription. CONCLUSIONS: The difference between 6MWD1 and 6MWD2 was consistent regardless of previous exposure to 6MWTs. A single 6MWT was as effective as 2 repeated 6MWTs for outcome measurement and exercise prescription. We therefore recommend that when 6MWDs are used for CR outcome measurement, either a single 6MWT be used or the number of 6MWTs performed be consistent at all assessment points.

Comparison of heart rate reserve, age predicted maximum heart rate and rate pressure product as predictors of future cardiovascular events following a negative dobutamine stress echocardiogram.

Background: Dobutamine stress echocardiography (DSE) is a commonly used diagnostic stress test for the assessment of various cardiac pathologies on patients unable to perform exercise. Unlike exercise, there is no reliable subjective termination end-point such as fatigue to rely on. Consequently, DSE's are often concluded at a predetermined age predicted maximal heart rate (APMHR) such as 85%. The aim of this study was to assess if APMHR, heart rate reserve (HRR) and the maximum rate pressure product (MRPP) are valid measures of future cardiovascular (CV) events in otherwise negative DSEs.Methods: Following exclusions, receiver operating curve (ROC) analyses were performed on 652 patients using CV events during the follow-up period (4.2 ± 1.8 years) as the outcome variable.Results: ROC analyses failed to produce a statistically valid model for MRPP (p = .227, area under curve (AUC)=0.55) with a sensitivity and specificity of 21.1% and 91.9%, respectively at the optimal cut point (14948 MRPP). To the contrary, APMHR produced a sensitivity and specificity of 74.7% and 60.9%, respectively (p < .0001, AUC = 0.715). HRR however, with a sensitivity and specificity of 67.4% and 68.2% (p < .0001, AUC = 0.718) was the only predictor of CV events following Cox analysis (p < .0001).Conclusions: This study demonstrates MRPP as a poor measure of CV event prediction during DSE. While an APMHR of 89.3% demonstrated a statistically valid model, HRR was the only predictor of CV events in otherwise negative DSEs.

Is downstream cardiac testing required in patients with reduced functional capacity and otherwise negative exercise stress test? A single center observational study.

BACKGROUND: Exercise stress testing (EST) in patients with poor functional capacity measured by time on treadmill is typically deemed inconclusive and usually leads to further downstream testing. The aim of this study was firstly to evaluate the maximum rate pressure product (MRPP) during initial EST to assessthe need for follow-up testing; and secondly to investigate if MRPP is better than age predicted maximum heart rate (APMHR) for diagnostic outcome based on follow up cardiovascular (CV) events in patients with inconclusive EST due to poor functional capacity. METHODS: From a total of 2761 tests performed, 236 tests were considered inconclusive due to poor functional capacity which were available for analysis. From receiver operating characteristic (ROC) analysis, a cut-off value for MRPP of 25000 was chosen using CV events as the outcome measure (sensitivity 97%, specificity 45%). Cases were then categorised into those with an MRPP > 25000 and < 25000. RESULTS: Regardless of treadmill time, any patient attaining an MRPP > 25000 had no abnormal downstream testing or CV events at 2 years follow-up. On ROC analysis MRPP outperformed APMHR for sensitivity and specificity (area under curve 0.76 vs. 0.59, respectively). CONCLUSIONS: The results suggest that regardless of functional capacity, individuals whose EST is terminated at maximal fatigue, with no electrocardiogram evidence or symptoms of myocardial ischemia and yields an MRPP > 25000, do not require further downstream testing. Furthermore, this group of patients, while not immune to future CV events, have significantly better outcomes than those not attaining a MRPP > 25000.

Handrail support produces a higher rate pressure product in apparently healthy non-treadmill users during maximal exercise testing.

OBJECTIVE: Exercise treadmill testing (ETT) is a well-established procedure for the diagnosis, prognosis and functional assessment of patients with suspected cardiovascular disease. The use of handrail support during ETT is often discouraged as this has been demonstrated to overestimate functional capacity. It is unknown if this increase in functional capacity translates to an increase in cardiac workload. The aim of this study was to investigate if the use of handrail support during maximal ETT produces an increase in cardiac workload when compared to no handrail support. APPROACH: Fifty-two consenting volunteers performed two maximal ETTs, one with handrail support and the other without, approximately one week apart. Participants were identified as either experienced treadmill users (treadmill use ⩾ once per fortnight) (n = 24) or inexperienced users (n = 28). Cardiac workload was quantified using rate pressure product (RPP) (systolic blood pressure (SBP) × heart rate (HR)) Main results: The average age of participants was 38.4 ± 11.4 years (44% male). Overall exercise duration was significantly prolonged by 44.4% with handrail support (with support 15:01 ± 2:54 min; without support 10:24 ± 2:09 min). Overall HR, SBP and maximum RPP were not significantly different between conditions. For the 28 inexperienced treadmill users maximum RPP was significantly higher during handrail support (7.5% increase) (with support 34 417 ± 4906; without support 31 821 ± 4565). SIGNIFICANCE: Handrail support overestimates functional capacity, however produces greater maximal RPP in inexperienced treadmill users. If accurate aerobic data is required during ETT, or subjects performing ETT are experienced treadmill users, handrail support should be discouraged. Non-treadmill users or subjects fearful of falling may benefit from handrail support, particularly when maximal cardiac workload is desired.

Comparison of Heart Rate Blood Pressure Product Versus Age-Predicted Maximum Heart Rate as Predictors of Cardiovascular Events During Exercise Stress Echocardiography.

Exercise stress echocardiograms (ESEs) are a functional cardiovascular (CV) test typically used for the investigation of coronary artery disease. ESEs are often terminated at a predetermined age-predicted maximum heart rate (APMHR) to facilitate timely acquisition of ultrasound images at peak exercise. Although an APMHR of 85% is often used, this has not been validated as a suitable termination end point. Heart rate blood pressure product (HRBPP) as an established measure of myocardial work may provide a more reliable assessment of cardiac workload. The aim of this study was to assess maximal HRBPP (MHRBPP) and APMHR as markers of cardiac workload during ESE, using CV events at mean follow-up as the outcome variable. After exclusions, 712 patients being investigated for ischemic heart disease, performed an ESE to volitional fatigue using the standard Bruce protocol. Patient demographics and test data were collected and patients followed for 4.4 ± 2.1 years. Cut-points for MHRBPP (25,060; area under curve 0.77) and APMHR (93.8% and 97.9%; area under curve 0.71; p = 0.12 for difference) were established from receiver operating characteristic analysis. Those achieving an APMHR >85% but MHRBPP <25,060 had significantly more CV events than achieving an MHRBPP >25,060 regardless of APMHR (p <0.05). In conclusion, the current study demonstrates the superior prognostic power of MHRBPP over APMHR alone for the prediction of future CV events in patients performing an otherwise negative ESE for the detection of myocardial ischemia.

Gray matter blood flow change is unevenly distributed during moderate isocapnic hypoxia in humans.

Hypoxia increases cerebral blood flow (CBF), but it is unknown whether this increase is uniform across all brain regions. We used H(2)(15)O positron emission tomography imaging to measure absolute blood flow in 50 regions of interest across the human brain (n = 5) during normoxia and moderate hypoxia. Pco(2) was kept constant ( approximately 44 Torr) throughout the study to avoid decreases in CBF associated with the hypocapnia that normally occurs with hypoxia. Breathing was controlled by mechanical ventilation. During hypoxia (inspired Po(2) = 70 Torr), mean end-tidal Po(2) fell to 45 +/- 6.3 Torr (means +/- SD). Mean global CBF increased from normoxic levels of 0.39 +/- 0.13 to 0.45 +/- 0.13 ml/g during hypoxia. Increases in regional CBF were not uniform and ranged from 9.9 +/- 8.6% in the occipital lobe to 28.9 +/- 10.3% in the nucleus accumbens. Regions of interest that were better perfused during normoxia generally showed a greater regional CBF response. Phylogenetically older regions of the brain tended to show larger vascular responses to hypoxia than evolutionary younger regions, e.g., the putamen, brain stem, thalamus, caudate nucleus, nucleus accumbens, and pallidum received greater than average increases in blood flow, while cortical regions generally received below average increases. The heterogeneous blood flow distribution during hypoxia may serve to protect regions of the brain with essential homeostatic roles. This may be relevant to conditions such as altitude, breath-hold diving, and obstructive sleep apnea, and may have implications for functional brain imaging studies that involve hypoxia.

Supervised moderate intensity exercise improves distance walked at hospital discharge following coronary artery bypass graft surgery--a randomised controlled trial.

BACKGROUND: This study aimed to determine whether a structured, inpatient (or Phase 1 cardiac rehabilitation), physiotherapy-supervised walking program, with or without musculoskeletal and respiratory exercises, might improve walking capacity and other parameters for patients undergoing coronary artery bypass graft surgery (CABG). METHODS: Ninety-three patients awaiting first-time CABG over a 12-month period were randomised to one of three post-operative physiotherapy regimens: 'standard intervention', consisting of gentle mobilisation; 'walking exercise', consisting of a physiotherapy-supervised, moderate intensity walking program; and 'walking/breathing exercise', consisting of the same moderate intensity walking program, musculoskeletal exercises and respiratory exercises. Primary outcomes; six-minute walking assessment (6MWA) distance, vital capacity and health-related quality of life, were measured pre-operatively, at discharge from hospital and at four weeks following discharge. RESULTS: Walking and walking/breathing exercise groups had significantly higher 6MWA distance (444+/-84 m, 431+/-98 m, respectively) than the standard intervention group (377+/-90 m) at discharge from hospital. There was no significant difference between intervention groups for 6MWA distance at four-week follow-up. There was no significant difference between intervention groups in terms of vital capacity and health-related quality of life. CONCLUSIONS: A physiotherapy-supervised, moderate intensity walking program in the inpatient phase following CABG improves walking capacity at discharge from hospital. The performance of respiratory and musculoskeletal exercises confers no additional benefit to the measured outcomes.

In patients with unilateral pleural effusion, restricted lung inflation is the principal predictor of increased dyspnoea.

BACKGROUND AND OBJECTIVE: The mechanism of dyspnoea associated with pleural effusion is uncertain. A cohort of patients requiring thoracoscopy for unilateral exudative effusion were investigated for associations between dyspnoea and suggested predictors: impaired ipsilateral diaphragm movement, effusion volume and restricted lung inflation. METHODS: Baseline Dyspnoea Index, respiratory function, and ultrasound assessment of ipsilateral diaphragm movement were assessed prior to thoracoscopy, when effusion volume was measured. Transitional Dyspnoea Index (change from baseline) was assessed 4 and 8 weeks after thoracoscopy. Pearson product moment assessed bivariate correlations and a general linear model examined how well total lung capacity (measuring restricted lung inflation), effusion volume and impaired diaphragm movement predicted Baseline Dyspnoea Index. Un-paired t tests compared the groups with normal and impaired diaphragm movement. RESULTS: 19 patients were studied (14 malignant etiology). Total lung capacity was associated with Baseline Dyspnoea Index (r = 0.68, P = 0.003). Effusion volume (r = -0.138, P = 0.60) and diaphragm movement (P = 0.09) were not associated with Baseline Dyspnoea Index. Effusion volume was larger with impaired diaphragm movement compared to normal diaphragm movement (2.16 ±SD 0.95 vs.1.16 ±0.92 L, P = 0.009). Total lung capacity was lower with impaired diaphragm movement compared to normal diaphragm movement (65.4 ±10.3 vs 78.2 ±8.6% predicted, P = 0.011). The optimal general linear model to predict Baseline Dyspnoea Index used total lung capacity alone (adjusted R2 = 0.42, P = 0.003). In nine participants with controlled effusion, baseline effusion volume (r = 0.775, P = 0.014) and total lung capacity (r = -0.690, P = 0.040) were associated with Transitional Dyspnoea Index. CONCLUSIONS: Restricted lung inflation was the principal predictor of increased dyspnoea prior to thoracoscopic drainage of effusion, with no independent additional association with either effusion volume or impaired ipsilateral diaphragm movement. Restricted lung inflation may be an important determinant of the dyspnoea associated with pleural effusion.

Exertional dyspnea associated with chest wall strapping is reduced when external dead space substitutes for part of the exercise stimulus to ventilation.

Chest wall strapping has been used to assess mechanisms of dyspnea with restrictive lung disease. This study examined the hypothesis that dyspnea with restriction depends principally on the degree of reflex ventilatory stimulation. We compared dyspnea at the same (iso)ventilation when added dead space provided a component of the ventilatory stimulus during exercise. Eleven healthy men undertook a randomized controlled crossover trial that compared four constant work exercise conditions: 1) control (CTRL): unrestricted breathing at 90% gas exchange threshold (GET); 2) CTRL+dead space (DS): unrestricted breathing with 0.6-l dead space, at isoventilation to CTRL due to reduced exercise intensity; 3) CWS: chest wall strapping at 90% GET; and 4) CWS+DS: chest strapping with 0.6-l dead space, at isoventilation to CWS with reduced exercise intensity. Chest strapping reduced forced vital capacity by 30.4 ± 2.2% (mean ± SE). Dyspnea at isoventilation was unchanged with CTRL+DS compared with CTRL (1.93 ± 0.49 and 2.17 ± 0.43, 0-10 numeric rating scale, respectively; P = 0.244). Dyspnea was lower with CWS+DS compared with CWS (3.40 ± 0.52 and 4.51 ± 0.53, respectively; P = 0.003). Perceived leg fatigue was reduced with CTRL+DS compared with CTRL (2.36 ± 0.48 and 2.86 ± 0.59, respectively; P = 0.049) and lower with CWS+DS compared with CWS (1.86 ± 0.30 and 4.00 ± 0.79, respectively; P = 0.006). With unrestricted breathing, dead space did not change dyspnea at isoventilation, suggesting that dyspnea does not depend on the mode of reflex ventilatory stimulation in healthy individuals. With chest strapping, dead space presented a less potent stimulus to dyspnea, raising the possibility that leg muscle work contributes to dyspnea perception independent of the ventilatory stimulus.NEW & NOTEWORTHY Chest wall strapping was applied to healthy humans to simulate restrictive lung disease. With chest wall strapping, dyspnea was reduced when dead space substituted for part of a constant exercise stimulus to ventilation. Dyspnea associated with chest wall strapping depended on the contribution of leg muscle work to ventilatory stimulation. Chest wall strapping might not be a clinically relevant model to determine whether an alternative reflex ventilatory stimulus mimics the intensity of exertional dyspnea.