Olson, Thomas P.

Patients with HFrEF exhibit severe exercise intolerance. One of the primary peripheral mechanisms contributing to exercise intolerance in patients with HFrEF is locomotor muscle group III/IV afferent feedback. However, it is unknown whether these afferents impact the central and peripheral responses during submaximal cycling exercise. Herein, we demonstrate that inhibition of locomotor muscle group III/IV afferent feedback elicited increases in stroke volume during submaximal exercise in HFrEF, but not in healthy controls.

Objectives To observe the weight change in Chinese youth during a 4-month COVID-19 lockdown, and the association between weight change and mental health, physical activity and sedentary time changes, and dietary habits. Design A retrospective observational study. Settings Two universities located in Zhejiang and Hunan provinces, China. Participants This study enrolled 12 889 college students whose body weight was measured before the lockdown (1 December 2019–20 January 2020) at the two universities, and reported their weight measured at home or community after the end of the lockdown (1–23 May 2020) via an online follow-up questionnaire. Primary and secondary outcome measures The primary outcome was the weight change in Chinese youth during a 4-month lockdown resulting from the COVID-19 pandemic. The secondary outcomes were the relationships of weight change to COVID-19-related stress, depression, anxiety, physical activity and sedentary time changes, and dietary habits. Results Participants’ ages ranged from 17 to 27 years ( M =19, SD=1) with 80.2% identified as female. The average absolute and relative changes in body weight were 2.6 (95% CI 2.0 to 3.2)) kg and 4.2% (95% CI 4.0% to 4.3%) for men, and 2.1 (1.9 to 2.4) kg and 4.2% (95% CI 3.9% to 4.4%) for women. An increase in overweight and obese individuals according to Asian cut-off points as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in men and women, respectively ( P <0.001), was observed. Weight gain was significantly associated with increased sedentary time and an increase in COVID-19-related stress and depression score. Conclusion The present study’s results suggest that the risk of weight gain in Chinese youth during the lockdown increased and that strategies to decrease sedentary time and improve mental health may be warranted to mitigate weight gain during and after the COVID-19 pandemic.

Background: This is the first systematic review and meta-analysis to investigate the effect of resistance training (RT) on survival and other cardiovascular outcomes including ischemic heart disease events and stroke. Methods: An experienced librarian searched databases up to September 25 th , 2017, for randomized trials and cohort studies that evaluated the effect of RT on survival and cardiovascular events in the general population. The databases included Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Two investigators conducted the screening process independently and in duplicate. Cochrane tools were used to assess the risk of bias in clinical trials and observational studies. We calculated hazard ratios and 95% confidence intervals using RevMan and fixed and random effect models and had a subgroup analysis based on doses of RT and for the combination of RT and aerobic exercise (AE) vs no exercise. Results: The search identified 1429 studies from which 10 (one randomized trial) met the inclusion criteria, including 338,254 participants with a mean follow up of 8.14 years. The meta-analysis showed that RT, in comparison with no exercises, is associated with 24% lower all-cause mortality and 48% lower mortality when combined with AE. Based on subgroup analysis, performing 1-2 sessions of RT/week is associated with lower all-cause mortality by 28% (HR 0.72, 95% CI 0.66-0.78) whereas > 5 sessions of RT/week has no association with all-cause mortality (HR 0.99, 95% CI 0.76-1.31). Further, RT alone or combined with AE is associated with lower CV mortality compared to no exercise (Figures). Finally, RT alone also showed a borderline association with lower all-cancer mortality. Heterogeneity was present for several comparisons, and subsequent analysis will explore sources of this variability. Using study design-specific Cochrane risk of bias tools, no major sources of bias were identified in the included studies. One cohort study looked at the effect of RT on coronary heart disease events and found 23% risk reduction in men, while no study specifically assessed the effect of RT on cerebrovascular outcomes. Conclusion: RT is associated with lower all-cause, CV and all-cancer mortality. RT appears to have an additive effect when combined with AE.

Introduction: Patients with hypertrophic cardiomyopathy (HCM) have lower peak oxygen uptake (VO2) than healthy peers. The mechanism of peak VO2 limitation in HCM has not been fully elucidated. Hypothesis: We assessed the hypothesis that resting echocardiographic parameters are predictive of peak VO2 in HCM. Methods: A retrospective review of adult HCM patients seen at a tertiary referral center from 2006-2012 was performed. Patients who underwent a comprehensive echocardiogram and cardiopulmonary treadmill exercise test within 1 week were included. Multivariate modeling was used to identify predictors of peak VO2 adjusting for age, sex, body mass index, beta blocker use, diabetes, smoking, systolic blood pressure, and obstructive HCM. Results: Five hundred and forty one patients met the inclusion criteria. The average age was 52 +/- 0.65 years, 62% were male, 78% had obstructive HCM, and 42% were NYHA class III or IV. Independent predictors of peak VO2 included averaged left ventricular (LV) longitudinal peak systolic strain (p<0.01) and right ventricular systolic pressure (RVSP) (p<0.01) (Figure 1). Obstructive versus non-obstructive HCM, grade of diastolic dysfunction, LV mass and wall thickness, left atrial volume index, right ventricular dysfunction and moderate or greater mitral or tricuspid regurgitation were not independent predictors of peak VO2. Conclusions: In conclusion, higher RVSP and less negative LV longitudinal peak systolic strain were moderate independent predictors of lower peak VO2. These findings confirm the hypothesis that resting echocardiographic parameters are predictive of peak VO2 in HCM. Further study of the relationship between echocardiographic findings and outcomes on cardiopulmonary exercise testing may help elucidate the mechanisms of exercise limitation in HCM.

Introduction: Impaired peak VO2 and obesity are known predictors of morbidity and mortality in Hypertrophic Cardiomyopathy (HCM). The purpose of this study is to determine the degree of exercise impairment due to excess weight in patients with HCM. Methods: Adult HCM patients who underwent cardiopulmonary treadmill testing at our tertiary referral center from 2006 - 2012 and had consented to research participation were identified retrospectively. Percent predicted peak VO2 was calculated by the Astrand formula for men and the Jones formula for women which adjust for age and gender. Baseline echocardiographic features obtained within 1 week of exercise testing and % predicted peak VO2 were compared among four groups of patients stratified by body mass index (BMI). Results: 510 patients were identified, with a mean age at diagnosis of 44.3 ± 16.1 years, 186 (36.5%) female. Mean BMI at the time of cardiopulmonary exercise testing was 29.7 ± 5.3 and 227 (44.6%) patients had a BMI ≥ 30. Overweight and obese patients were older and were more likely to be male than their normal weight peers. However, there was no significant difference in ejection fraction (EF), resting left ventricular outflow tract gradient, right ventricular systolic pressure (RVSP), or septal thickness among the groups. HCM patients show impaired peak VO2 across all BMI groups. While peak VO2 increased progressively across BMI groups consistent with greater O2 demand generated by higher body weight, the adjusted peak VO2 in mL/kg/min fell progressively, indicating progressively greater performance impairment with increasing BMI despite similar degrees of cardiac impairment (p <0.0001) (Table 1). Conclusion: Increased BMI is associated with reduced exercise performance in a graded manner in HCM patients independent of cardiac impairment identified on echocardiography.

Introduction: Neural feedback from skeletal muscle during exercise contributes to changes in pulmonary pressures in healthy individuals. Heart failure patients (HF) often develop pulmonary hypertension; however, the relationship between muscle afferent feedback and the pulmonary vasculature in HF remains unclear. Hypothesis: We examined the influence of metaboreceptor stimulation on pulmonary vascular capacitance using a validated non-invasive gas exchange equivalent (GX CAP ) in HF. Methods: Eleven HF patients (age 51±5 yrs; EF, 32±3%; NYHA class, 1.6±0.2) and 11 controls (CTL; age 43±3 yrs) completed 3 cycling session (4-min at 60% of peak oxygen consumption, VO 2 ). Session one: baseline control trial. Sessions 2 and 3: bilateral upper-thigh tourniquets inflated suprasystolic for 2 min at end-exercise (regional circulatory occlusion, RCO) with or without addition of inspired CO 2 to maintain end-exercise end-tidal CO 2 (P ET CO 2 ) (RCO+CO 2 ) (randomized). Rest, exercise, and recovery heart rate (HR), P ET CO 2 , and VO 2 were measured. O 2 pulse (VO 2 /HR) and GX CAP (O 2 pulseхP ET CO 2 ) were calculated. Results: During all conditions at end-exercise, HF demonstrated significantly lower GX CAP compared to CTL (p<0.01). Percent change in GX CAP from end-exercise to 2 min post-exercise was attenuated in HF compared to CTL (41±5% vs 64±1%, respectively, p<0.01) during the baseline trial. During RCO, HF had a 55±6% reduction in GX CAP from end-exercise compared to 77±2% in CTL (p<0.01). During RCO+CO 2 , HF had a 49±4% reduction in GX CAP from end-exercise compared to 69±2% in CTL (p<0.01). GX CAP was similar between sessions within HF. The CTL group demonstrated an attenuated return of GX CAP during RCO compared to both baseline and RCO+CO 2 (p<0.01) with no difference between baseline and RCO+CO 2 . Conclusion: These data suggest the exercise mediated rise and post-exercise recovery of pulmonary vascular capacitance are attenuated in HF during constant-load submaximal exercise compared to CTL. Additionally, our data confirm previous reports that locomotor muscle afferent feedback influences pulmonary vascular capacitance in CTL; however, this model of locomotor muscle metaboreflex stimulation appears to a differential response in HF compared to CTL.

Introduction: Physical activity (PA) is known to be effective in treating and preventing many lifestyle diseases including CVD, stroke, depression, type II diabetes, Alzheimer’s disease, as well as breast and colon cancer. To date the direct medical cost-savings of PA as a medical intervention are poorly understood. Hypothesis: We hypothesized that a 10% increase in the proportion of US citizens who meet the minimum weekly exercise requirements of 150 minutes per week would lead to savings in direct medical costs (DMC) and cases prevented, as related to the above diseases. Methods: Population Attributable Risk (PAR) was calculated as PAR= (1+Prf x (RR-1))/(Prf x(RR-1)), where Prf is the percentage of the U.S. population not meeting minimum exercise requirements and RR is the relative risk of disease for sedentary versus physically active individuals. Prf and RR data were retrieved from the most recent and comprehensive meta-analyses and systematic reviews. PAR was calculated for each disease under two conditions; first, Prf was equal to the current percent (9.6%) of the population estimated to achieve the minimum weekly PA requirements. Second, Prf was equal to the initial Prf plus 10 percent (19.6%). For each condition the following were calculated: Attributable DMC=(PAR x DMC), preventable cases=(PAR x Prevalence) and Savings=(Condition 2- Condition 1). Results: The Prevalence, RR, PAR and DMC are provided in Table 1. This table also describes the potential savings in DMC and new cases by improving the Prf by 10%. A 10% increase in US citizens who meet the minimum weekly exercise requirements could lead to a total savings of 10.78 billion USD in DMC and 2.1 million cases prevented related to the studied diseases. Conclusion: A healthcare system directed PA intervention that effectively leads to a 10% increase in US citizens that meet minimum weekly exercise requirements and costs less than 10.78 billion dollars has the potential to be cost-effective, and prevent and treat, millions of cases in the United States.

Locomotor and respiratory muscle feedback via group III/IV afferents influences the blood pressure response during exercise. Specifically, stimulation of the inspiratory and locomotor muscle afferents (via inspiratory loading (IL) and subsystolic circulatory occlusion (CUFF), respectively) increases the blood pressure response during exercise with combined IL and CUFF (IL+CUFF) further augmenting the blood pressure response. Sex differences in blood pressure have been observed in both IL and CUFF when investigated individually, while the influence of sex hormones is unclear. It is unknown if sex and menstrual cycle phase influences the blood pressure response to IL+CUFF during exercise. Purpose To determine if sex and menstrual cycle phase influence the blood pressure response during IL+CUFF in men and premenopausal women. We hypothesized that women will exhibit attenuated increases in blood pressure compared to age‐matched men during IL, CUFF, and IL+CUFF, while no differences would be present across the menstrual cycle. Methods To date, 13 adults (7M/6W; M: 28±6 vs. W: 29±4 yrs, p=0.30; M: 27±5 vs. W: 25±2 kg/m 2 , p=0.85) have participated in this study. Participants performed four 10 min exercise bouts at 40% of their peak oxygen uptake. The participants performed spontaneously breathing (SB) during the first 5 minutes and voluntary hyperventilation (i.e. breathing frequency of 40 breaths/min with 50% duty cycle) during the last 5 minutes. During this last 5 min, IL (30% maximal inspiratory pressure), CUFF (80 mmHg), IL + CUFF, or no intervention (CTL) occurred in a randomized order. Women completed the study protocol twice, once during midluteal (ML) phase and once during early follicular (EF) phase. Blood pressure was measured using manual sphygmomanometry. Changes in systolic blood pressure (ΔSBP), diastolic blood pressure (ΔDBP), and mean arterial pressure (ΔMAP) were determined by subtracting values obtained during IL, CUFF, IL+CUFF, or CTL from SB. Results There were no significant differences in ΔMAP across groups during CTL (M: 5±5; ML 2±2; EF: 2±2 mmHg, all p>0.24), IL (M: 11±4; ML 10±2; EF 12±5 mmHg, all p>0.60), CUFF (M: 19±6; ML 16±4; EF 20±2 mmHg, all p>0.20), or IL + CUFF (M: 24±5; ML 23±6; EF 23±3 mmHg, all p>0.82). There were no significant differences in ΔSBP across groups during CTL (M: 5±4; ML 5±4; EF: 8±13 mmHg, all p>0.49), IL (M: 17±6; ML 17±5; EF 19±8 mmHg, all p>0.63), CUFF (M: 24±12; ML 23±7; EF 28±5 mmHg, all p>0.31), or IL + CUFF (M: 34±8; ML 33±11; EF 33±8 mmHg, all p>0.94). There were no significant differences in ΔDBP across group during CTL (M: 5±8; ML 0±1; EF: −1±4 mmHg, all p>0.05), IL (M: 8±3; ML 7±2; EF 9±4 mmHg, all p>0.71), CUFF (M: 16±4; ML 13±4; EF 16±2 mmHg, all p>0.20), or IL + CUFF (M: 19±6; ML 18±6; EF 18±3 mmHg, all p>0.75). Conclusion With this limited sample size, our data suggest that neither sex nor menstrual cycle phase influences the blood pressure response with IL, CUFF or IL+CUFF. Support or Funding Information NIH HL126638 AHA 18POST3990251 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Introduction Peripheral nervous system feedback arising from mechanically and metabolically sensitive afferents (Group III/IV, respectively) are central components of the exercise pressor reflex. Experimentally, locomotor venous distention can be simulated via subsytolic regional circulatory occlusion (SubRCO) thereby augmenting the exercise pressor reflex. Furthermore, high pedal frequency increases type II muscle fiber recruitment during exercise likely increasing non‐oxidative metabolism. To date, studies investigating the influence of aging on the exercise pressor reflex have presented conflicting data with most utilizing small muscle mass exercise (e.g. handgrip). Therefore, the purpose of this study was to determine the influence of SubRCO, pedal frequency, and the combination thereof on blood pressure (BP) during exercise in older and younger adults. We hypothesized that during exercise 1) independent of pedal frequencies and age, SubRCO will augment BP and 2) older adults will have greater increases in BP at high pedal frequencies with and without SubRCO compared younger adults. Methods 10 younger (22±2 yrs; 4M/6W; 24±4 kg/m 2 ) and 10 older (63±10yrs; 4M/6W; 24±4 kg/m 2 ) adults participated in two study visits each consisting of two cycling exercise sessions at 20 W, with bilateral upper thigh pressure cuffs. Participants engaged in 3 minutes of exercise at 35 (LOW) or 100 (HIGH) rpm with 5 additional minutes of exercise at that rpm with no cuffing (CTL) or SubRCO in randomized order. Systolic and diastolic blood pressure (SBP and DBP, respectively) were measured via manual sphygmomanometry. Mean arterial pressure (MAP) was calculated as (SBP‐DBP)/3+DBP and the changes in MAP from rest are reported. Results During LOW, SubRCO resulted in greater MAP than CTL in younger (CTL: 4±7; SubRCO: 13±7 mmHg) and older adults (CTL: 4±6; SubRCO: 13±4 mmHg) (both p<0.01). During HIGH, SubRCO resulted in greater MAP than CTL in younger (CTL: 7±4; SubRCO: 20±6 mmHg) and older adults (CTL: 20±9; SubRCO: 31±8 mmHg) (both p<0.01). Younger and older adults had greater increases in MAP during HIGH CTL and SubRCO compared to LOW CTL and SubRCO, respectively (all, p<0.01). Within LOW, there were no differences between younger and older adults during CTL or SubRCO (all, p>0.05). Within HIGH, older adults had greater increases in MAP than younger adults during CTL and SubRCO (both p<0.01). Conclusion These data support the hypothesis that older compared to younger adults have a greater BP response at higher pedal frequencies during exercise. Our results suggest that aging contributes to a greater exercise pressor response to exercise, possibly due to greater feedback from group III/IV afferents. Support or Funding Information NIH HL126638AHA 18POST3990251 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

INTRODUCTION Heart failure (HF) is characterized by reduced exercise capacity resulting from central and peripheral mechanisms. A primary peripheral mechanism is augmented neural feedback (via group III/IV afferents) arising from the locomotor muscles. This enhanced locomotor neural feedback may result from a variety of mechanisms including increased 1) metabo and/or mechanoreceptor expression, 2) metabolite production, and/or 3) mechano/metaboreceptor sensitivity. Previous studies have shown elevated expression of purinergic 2X3 (P2X3) and cyclooxygenase (COX‐2) in HF compared to sham animal models. However, it is unknown if metabo and/or mechanoreceptor (e.g., Piezo 1 and 2) expression are elevated in human HF. Further, it is unclear if altered receptor expression is related to the cardiovascular and ventilatory responses during exercise attributed to locomotor neural afferent feedback. The purpose of this study was to 1) determine if differences exist in the expression of skeletal muscle proteins associated with metabo/mechanoreflex activity between healthy individuals (CTL) and HF patients and 2) determine relationships between protein expression and the change in ventilatory and cardiovascular responses with locomotor muscle afferent inhibition during exercise. We hypothesized that 1) HF patients will demonstrate greater skeletal muscle protein expression associated with mechano/metaboreflex activity and 2) the increased protein expression will be associated with changes in ventilation, mean arterial pressure (MAP), and catecholamines during locomotor muscle afferent feedback inhibition in HF patients. METHODS In a randomized, placebo controlled cross‐over design, 10 CTL and 6 systolic HF (Age: 60±12 vs. 60±4 yrs, p=0.96; BMI: 26±3 vs. 31±5 kg/m 2 , p=0.01, respectively) patients completed cycling exercise at 60%VO 2 peak with lumbar intrathecal fentanyl or sham. Arterial blood pressure and catecholamines were measured via radial artery catheter during exercise. On a follow up visit, a muscle biopsy from the vastus lateralis was performed to isolate and measure COX‐2, P2X3, transient receptor potential vanilloid type 1 (TRPV1), Piezo 1, and Piezo 2 protein expression. RESULTS Protein expression of P2X3, COX‐2, and TRPV1 were greater in HF compared to CTL (all, p<0.05), with no difference between groups in Piezo 1 and 2 protein expression (p>0.05). HF compared to CTL had a greater decrease in ventilation with fentanyl compared to sham (−11±8 vs. −3±9%, p=0.04, respectively), with no difference between groups in MAP or norepinephrine (p>0.05). In HF, COX expression was negatively related to the change in ventilation (r= −0.87, p=0.02), MAP (r= −0.93, p<0.01), and norepinephrine (r= −0.85, p=0.03) with fentanyl. CONCLUSIONS These data demonstrate that metaborecptors (i.e. P2X3, COX‐2, and TRPV1) are elevated in HF compared to CTL. Furthermore, protein expression of COX‐2 was related to the cardiovascular and ventilatory changes observed with fentanyl in HF patients. These findings suggest that elevated expression of metaboreflex associated proteins contribute to the augmented locomotor muscle afferent feedback during exercise in HF. Support or Funding Information NHLBI RO1 HL126638 AHA 18POST3990251 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .