Smith, Joshua R.

Background Previous studies have demonstrated that the near‐infrared spectroscopy venous occlusion technique (NIRS‐VOT) provides a valid assessment of regional forearm muscle blood flow; however, day‐to‐day reproducibility of hemodynamic variables derived from the NIRS‐VOT remains to be determined, particularly across the range of physiological blood flows observed during handgrip exercise. Purpose The purpose of this study was to evaluate the day‐to‐day reproducibility of forearm hemodynamics assessed via the NIRS‐VOT. Methods Near‐infrared spectroscopy (NIRS) data were obtained from the flexor digitorum superficialis muscle on the right arm of 14 young, healthy adults (age: 27 ± 6 yrs; BMI: 24.6 ± 2.8 kg·m −2 ). The NIRS‐VOT was performed via rapid inflation of a pneumatic cuff placed on the upper arm for approximately 10 s. The NIRS‐VOT was performed at rest, and immediately after a 15 s isometric handgrip contraction at 20%, 40% and 60% of the subject’s maximum voluntary contraction. Measurements were repeated 3–5 times. Participants returned to the laboratory for a second visit on a separate day, and repeated the same number of measurements. Forearm blood flow (FBF), and blood pressure were measured on a beat‐by‐beat basis, and forearm vascular conductance (FVC) was calculated. FBF and FVC were subsequently compared for day‐to‐day reproducibility. Results FBF and FVC significantly increased with the intensity of handgrip exercise ( P < 0.05); however, these measures of forearm hemodynamics were not significantly different ( P >0.05) between Day 1 and Day 2 at each exercise‐intensity (Table ). Conclusion The findings of the present study indicate that the NIRS‐VOT provides a reliable assessment of regional forearm muscle hemodynamics across a physiological range of blood flows incurred by isometric handgrip exercise. Support or Funding Information MJJ is funded by the NIH (R‐35‐HL139854) and the Mayo Foundation. CCW is supported by the NIH training grant (5T32DK007352‐39), JRS is supported by AHA (18POST3990251), and TJC is funded by AFAR Postdoctoral Transition Award (DIAMOND18161). FBF and FVC on experimental days Day 1 Day 2 P ‐value FBF , mL · min − 1 · 100mL − 1 (tissue) Rest 2.0 ± 0.5 0.8 ± 0.2 0.001 20% MVC 14.4 ± 2.65 15.4 ± 2.4 0.679 40% MVC 26.0 ± 5.19 28.0 ± 4.3 0.606 60% MVC 39.4 ± 6.39 47.4 ± 7.7 0.858 FVC , mL · min − 1 · 100 mmHg − 1 Rest 170 ± 47.3 72 ± 16.4 0.001 20% MVC 1297 ± 227.8 1454 ± 209.6 0.380 40% MVC 2496 ± 492.8 2656 ± 434.0 0.912 60% MVC 3820 ± 659.1 4542 ± 744.7 0.535 MVC , kg 49.4 ± 3.0 47.9 ± 2.6 0.721 Abbreviations: FBF, forearm blood flow; FVC, forearm vascular conductance; MVC, maximal voluntary contraction. Values are presented as means ± SE. P values indicate comparison between days 1 and 2.

Reflexes arising from the respiratory and locomotor muscles influence cardiovascular regulation during exercise. However, it is unclear how the respiratory and locomotor muscle reflexes interact when simultaneously stimulated. Herein, we demonstrate that stimulation of the respiratory and locomotor muscle reflexes yielded additive cardiovascular responses during submaximal exercise.

New Findings What is the central question of this study? How do locomotor muscle metabo‐ and mechanoreceptor expression compare in heart failure patients and controls? Do relationships exist between the protein expression and cardiopulmonary responses during exercise with locomotor muscle neural afferent feedback inhibition? What is the main finding and its importance? Heart failure patients exhibited greater protein expression of transient receptor potential vanilloid type 1 and cyclooxygenase‐2 than controls. These findings are important as they identify receptors that may underlie the augmented locomotor muscle neural afferent feedback in heart failure. AbstractHeart failure patients with reduced ejection fraction (HFrEF) exhibit abnormal locomotor group III/IV afferent feedback during exercise; however, the underlying mechanisms are unclear. Therefore, the purpose of this study was to determine (1) metabo‐ and mechanoreceptor expression in HFrEF and controls and (2) relationships between receptor expression and changes in cardiopulmonary responses with afferent inhibition. Ten controls and six HFrEF performed 5 min of cycling exercise at 65% peak workload with lumbar intrathecal fentanyl (FENT) or placebo (PLA). Arterial blood pressure and catecholamines were measured via radial artery catheter. A vastus lateralis muscle biopsy was performed to quantify cyclooxygenase‐2 (COX‐2), purinergic 2X3 (P2X3), transient receptor potential vanilloid type 1 (TRPV1), acid‐sensing ion channel 3 (ASIC3), Piezo 1 and Piezo 2 protein expression. TRPV1 and COX‐2 protein expression was greater in HFrEF than controls (both P < 0.04), while P2X3, ASIC3, and Piezo 1 and 2 were not different between groups (all P > 0.16). In all participants, COX‐2 protein expression was related to the percentage change in ventilation (r = −0.66) and mean arterial pressure (MAP) (r = −0.82) (both P < 0.01) with FENT (relative to PLA) during exercise. In controls, TRPV1 protein expression was related to the percentage change in systolic blood pressure (r = −0.77, P = 0.02) and MAP (r = −0.72, P = 0.03) with FENT (relative to PLA) during exercise. TRPV1 and COX‐2 protein levels are elevated in HFrEF compared to controls. These findings suggest that the elevated TRPV1 and COX‐2 expression may contribute to the exaggerated locomotor muscle afferent feedback during cycling exercise in HFrEF.

ABSTRACT The present investigation tested the hypotheses that there would be greater prevalence of expiratory flow limitation (EFL) in endurance-trained (ET) youth cyclists compared with a recreationally active control (CON) group. METHODS Twelve ET youth male cyclists (16.3 ± 1.0 yr (13–18 yr), 176.5 ± 6.2 cm, 64.2 ± 5.9 kg) and 12 CON subjects (17.6 ± 2.2 yr (13–18 yr), 177.9 ± 7.1 cm, 74.8 ± 11.2 kg) completed an incremental exercise test to determine peak oxygen consumption (V˙O 2peak ) on a cycle ergometer. Maximal flow volume loops (MFVL), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), FEV 1 /FVC, forced expiratory flow between 25% and 75% of FVC, and peak expiratory flow were assessed before and after exercise, with inspiratory capacity maneuvers and dyspnea ratings measured in the last 20 s of each stage. EFL was quantified as the percentage of the expiratory tidal volume that overlapped with the maximal flow volume loop. RESULTS V˙O 2peak , dyspnea ratings at peak, and ventilation were higher in the ET compared with CON group ( P < 0.05). The ET group experienced greater EFL prevalence at V˙O 2peak , with 11 of 12 subjects exhibiting EFL compared with 5 of 12 subjects in the CON group ( P = 0.014). When matched for absolute ventilation of 20, 40, 60, 80, and 100 L·min −1 , there were no differences in EFL severity between the ET and CON groups ( P = 0.473). CONCLUSIONS Elite youth male cyclists have a greater prevalence of EFL at maximal exercise than do CON subjects who are similar in age, height, and lung size. Future research should determine whether EFL in youth ET male cyclists may limit their exercise performance.

Aims Patients with hypertrophic obstructive cardiomyopathy (HOCM) have impaired exercise capacity. The gold standard therapy for patients with HOCM is septal myectomy surgery; however, changes in maximum oxygen uptake (VO2peak) following myectomy are variable, with VO2peak decreasing in some patients. Therefore, we evaluated changes in VO2peak following surgical myectomy to determine clinical predictors of those exhibiting decreased VO2peak post-myectomy. Methods HOCM patients ( N = 295) who performed symptom limited cardiopulmonary exercise testing prior to and following surgical myectomy were included for analysis. The VO2peak non-responder group ( n = 128) was defined as <0% change in VO2peak from pre- to post-myectomy. Step-wise regression models using demographics, clinical, and physiologic characteristics were created to determine predictors of hypertrophic cardiomyopathy patients in the VO2peak non-responder group. Results Independent predictors of the VO2peak non-responder group included higher pre-myectomy VO2peak (% predicted), older age, women, history of dyslipidemia, lack of cardiac rehabilitation enrollment, and lower body mass index (all p < 0.03). Forty-three (14.6%) patients reached the primary end-point of all-cause mortality during a median follow up of 11.25 years (interquartile range 6.94 to 16.40). After adjustment for age, sex, beta-blocker use, coronary artery disease history, and body mass index, the VO2peak non-responder group had greater risk of death compared with the VO2peak responder group (adjusted hazard ratio: 1.77, 95% confidence interval: 1.06–3.34, p = 0.01). Conclusion This large hypertrophic cardiomyopathy cohort demonstrated that demographic (i.e. female sex), lack of cardiac rehabilitation enrollment, and cardiovascular risk factors (i.e. history of dyslipidemia) are predictive of those patients that did not exhibit increases in VO2peak following septal myectomy surgery.

It is unknown whether central hemodynamics are impaired during exercise in chronic obstructive pulmonary disease (COPD) patients. We hypothesized that, at a similar absolute V̇o2 during exercise, COPD patients would have a lower stroke volume and cardiac output compared with healthy controls. Furthermore, we hypothesized that greater static hyperinflation [ratio of inspiratory capacity to total lung capacity (IC/TLC)] and expiratory intrathoracic pressure would be significantly related to the lower cardiac output and stroke volume responses in COPD patients. Clinically stable COPD ( n = 13; FEV1/FVC: 52 ± 13%) and controls ( n = 10) performed constant workload submaximal exercise at an absolute V̇o2 of ~1.3 L/min. During exercise, inspiratory capacity maneuvers were performed to determine operating lung volumes and cardiac output (via open-circuit acetylene rebreathe technique) and esophageal pressure were measured. At similar absolute V̇o2 during exercise ( P = 0.81), COPD had lower cardiac output than controls (COPD: 11.0 ± 1.6 vs. control: 12.2 ± 1.2 L/min, P = 0.03) due to a lower stroke volume (COPD: 107 ± 13 vs. control: 119 ± 19 mL, P = 0.04). The heart rate response during exercise was not different between groups ( P = 0.66). FEV1 (%predicted) and IC/TLC were positively related to stroke volume ( r = 0.68, P = 0.01 and r = 0.77, P < 0.01). Last, esophageal pressure-time integral during inspiration was positively related to cardiac output ( r = 0.56, P = 0.047). These data demonstrate that COPD patients have attenuated cardiac output and stroke volume responses during exercise compared with control. Furthermore, these data suggest that the COPD patients with the most severe hyperinflation and more negative inspiratory intrathoracic pressures have the most impaired central hemodynamic responses. NEW & NOTEWORTHY Chronic obstructive pulmonary disease leads to cardiac structural changes and pulmonary derangements that impact the integrative response to exercise. However, it is unknown whether these pathophysiological alterations influence the cardiac response during exercise. Herein, we demonstrate that COPD patients exhibit impaired central hemodynamics during exercise that are worsened with greater hyperinflation.

The measurement of peak oxygen uptake (VO2peak) is an important metric for evaluating cardiac transplantation (HTx) eligibility. However, it is unclear which factors (e.g., recipient demographics, clinical parameters, cardiac rehabilitation (CR) participation) influence VO2peak following HTx. Consecutive HTx patients with cardiopulmonary exercise testing (CPET) between 2007–2016 were included. VO2peak was measured from CPET standard protocol. Regression analyses determined predictors of the highest post-HTx VO2peak (i.e., quartile 4: VO2peak > 20.1 mL/kg/min). One hundred-forty HTx patients (women: n = 41 (29%), age: 52 ± 12 years, body mass index (BMI): 27 ± 5 kg/m2) were included. History of diabetes (Odds Ratio (OR): 0.17, 95% Confidence Interval (CI): 0.04–0.77, p = 0.021), history of dyslipidemia (OR: 0.42, 95% CI: 0.19–0.93, p = 0.032), BMI (OR: 0.90, 95% CI: 0.82–0.99, p = 0.022), hemoglobin (OR: 1.29, 95% CI: 1.04–1.61, p = 0.020), white blood cell count (OR: 0.81, 95% CI: 0.66–0.98, p = 0.033), CR exercise sessions (OR: 1.10, 95% CI: 1.04–1.15, p < 0.001), and pre-HTx VO2peak (OR: 1.17, 95% CI: 1.07–1.29, p = 0.001) were significant predictors. Multivariate analysis showed CR exercise sessions (OR: 1.10, 95% CI: 1.03–1.16, p = 0.002), and pre-HTx VO2peak (OR: 1.16, 95% CI: 1.04–1.30, p = 0.007) were independently predictive of higher post-HTx VO2peak. Pre-HTx VO2peak and CR exercise sessions are predictive of a greater VO2peak following HTx. These data highlight the importance of CR exercise session attendance and pre-HTx fitness in predicting VO2peak post-HTx.

Hypertrophic obstructive cardiomyopathy (HOCM) patients exhibit compromised peak exercise capacity (VO2peak). Importantly, severely reduced VO2peak is directly related to increased morbidity and mortality in these patients. Therefore, we sought to determine clinical predictors of VO2peak in HOCM patients. HOCM patients who performed symptom-limited cardiopulmonary exercise testing between 1995 and 2016 were included for analysis. Peak VO2 was reported as absolute peak VO2, indexed to body weight and analyzed as quartiles, with quartile 1 representing the lowest VO2peak. Step-wise regression models using demographic features and clinical and physiologic characteristics were created to determine predictors of HOCM patients with the lowest VO2peak. We included 1177 HOCM patients (age: 53 ± 14 years; BMI: 24 ± 12 kg/m2) with a VO2peak of 18.0 ± 5.6 mL/kg/min. Significant univariate predictors of the lowest VO2peak included age, female sex, New York Health Association (NYHA) class, BMI, left atrial volume index, E/e’, E/A, hemoglobin, N-terminal pro b-type natriuretic peptide (NT-proBNP), and a history of diabetes, hypertension, stroke, atrial fibrillation, or coronary artery disease. Independent predictors of the lowest VO2peak included age (OR, CI: 1.03, 1.02–1.06; p < 0.0001), women (4.66, 2.94–7.47; p = 0.001), a history of diabetes (2.05, 1.17–3.60; p = 0.01), BMI (0.94, 0.92–0.96; p < 0.0001), left atrial volume index (1.07, 1.05–1.21; p = 0.04), E/e’ (1.05, 1.01–1.08; p = 0.004), hemoglobin (0.76, 0.65–0.88; p = 0.0004), and NT-proBNP (1.72, 1.42–2.11; p < 0.0001). These findings demonstrate that demographic factors (i.e., age and sex), comorbidities (e.g., diabetes and obesity), echocardiography indices, and biomarkers (e.g., hemoglobin and NT-proBNP) are predictive of severely compromised VO2peak in HOCM patients.