Berg, Jessica

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 Heart failure (HF) patients demonstrate augmented ventilation for a given metabolic demand which results in increased respiratory muscle work and subsequent competition for blood flow between the respiratory and locomotor muscle beds. Unloading the respiratory muscles during submaximal exercise has been shown to increase leg oxygen uptake (VO 2 ) in HF patients due increased leg blood flow via increased cardiac output and redistribution of cardiac output from the respiratory to locomotor muscles. It has been suggested that increased leg VO 2 following respiratory muscle unloading in HF during submaximal exercise is due to augmented convective O 2 transport in HF; however, it is unclear if diffusive O 2 transport also increases with respiratory muscle unloading. We hypothesized that respiratory muscle unloading during submaximal exercise will lead to increased leg VO 2 due to combined increases in convective and diffusive O 2 transport. Methods Ten HF patients with reduced systolic function (6M/4W; 53±15 yrs; BMI: 29±6 kg/m 2 ) were recruited. Patients performed two submaximal exercise bouts (i.e. with and without respiratory muscle unloading (via mechanical ventilator) (RM unloading and control (CTL), respectively)). During exercise, leg blood flow (Q L ) was measured via thermodilution. Intrathoracic pressure was measured via esophageal balloon. Radial arterial and femoral venous blood gases were measured. Blood gases were used to calculate arterial and venous oxygen content (CaO 2 and CvO 2 , respectively). Leg VO 2 was calculated as Q L multiplied by the difference between CaO 2 ‐CvO 2 . Leg O 2 delivery was calculated as Q L multiplied by CaO 2 . Leg diffusion capacity (DO 2 ) was calculated as leg VO 2 divided by femoral venous partial pressure of O 2 . Results From CTL to RM unloading, leg VO 2 increased during submaximal exercise (0.7±0.3 vs. 1.0±0.4 L/min, p<0.01, respectively). From CTL to RM unloading, leg O 2 delivery increased during submaximal exercise (0.9±0.4 vs. 1.4±0.5 L/min, p<0.01, respectively), whereas CaO 2 ‐CvO 2 was not different (14.1±3.0 vs. 14.2±3.2 mL/dL, p=0.57, respectively). From CTL to RM unloading, leg DO 2 increased during submaximal exercise (30.4±10.8 vs. 49.7±18.6 mL/mmHg, p<0.01, respectively). There was a negative relationship between the degree of RM unloading (i.e. percent decrease in mean inspiratory esophageal pressure) and percent increase in leg DO 2 with RM unloading (r= −0.77, p<0.01). Conclusion Our results demonstrate that unloading the respiratory muscles leads to increased leg VO 2 due to convective and diffusive O 2 transport during submaximal exercise in HF patients. These findings suggest that the naturally occurring respiratory muscle work in HF compromises convective and diffusive O 2 transport and thus constrains leg VO 2 during submaximal exercise in HF. 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 .

Objective Cardiovascular adjustments to exercise, including increases in blood pressure (MAP) and heart rate, occur in response to several neural mechanisms. Specifically, stimulation of respiratory (via inspiratory loading (IL)) and locomotor muscle (via subsystolic cuff inflation (CUFF)) neurologic feedback via group III/IV afferents augments the MAP response during exercise. Further, we have recently shown that simultaneous stimulation of the respiratory and locomotor muscle afferents during exercise potentiates the MAP increase compared to when these reflexes are stimulated individually. To date, interventional strategies to attenuate the augmented MAP during IL+CUFF have not been investigated. Previous studies have shown that inspiratory muscle training (IMT) attenuates the IL‐induced increase in MAP at rest in healthy adults. We hypothesized that 8 weeks of IMT will attenuate the IL+CUFF‐induced increase in MAP during exercise in healthy adults. Methods Twenty adults were recruited and randomized to the IMT (n=10) or sham group (n=10). Participants performed 8 weeks of IMT twice a day, 7 days a week at 50% (IMT) or 10% (sham) maximum inspiratory pressure (MIP). On separate visits, participants performed an incremental cycling test to volitional fatigue and a 10 min cycling exercise bout at 40% maximal oxygen uptake Pre‐ and Post‐IMT. The exercise bout consisted of 5 min of spontaneous breathing followed by 5 min of voluntary hyperventilation (i.e. breathing frequency of 40 breaths per min) with IL (30% MIP) and bilateral locomotor subsystolic cuff inflation (80 mmHg). Systolic and diastolic blood pressure (SBP and DBP, respectively) were measured using manual sphygmomanometry and MAP was calculated. SBP and MAP were reported as the change from rest. Dyspnea was measured via Borg scale (1–10). Results After 8 weeks, MIP increased in the IMT (Pre: 99±26 vs. Post: 127±26 cmH 2 O, p<0.05), but not the sham group (Pre: 126±29 vs. Post: 129±28 cmH 2 O, p>0.05). Pre‐IMT, the increase in MAP with IL+CUFF was not different between groups (IMT: 28±6 vs. sham: 31±7 mmHg) (p>0.05). Post‐IMT, the increase in MAP with IL+CUFF was attenuated in IMT, but not sham (IMT: 23±7 vs. sham: 32±5 mmHg) (p<0.05). Pre‐IMT, the increase in SBP with IL+CUFF was not different between groups (IMT: 49±12 vs. sham: 53±16 mmHg) (p>0.05). Post‐IMT, the increase in SBP with IL+CUFF was attenuated in IMT, but not sham (IMT: 42±12 vs. sham: 57±14 mmHg) (both, p<0.05). The increase in DBP with IL+CUFF was not different between groups Pre or Post‐IMT (both, p>0.05). Lastly, dyspnea was not different Pre‐IMT between groups (IMT: 4±3 vs. sham: 4±2 Borg (1–10)) (p>0.05), but was lower in the IMT, but not sham Post‐IMT (IMT: 2±2 vs. sham: 4±1 Borg (1–10)) (p<0.05). Conclusions These data demonstrate that IMT attenuates the MAP response when the respiratory and locomotor afferents are stimulated simultaneously. These findings have important clinical implications for populations that exhibit exaggerated respiratory and locomotor muscle reflexes during exercise. Support or Funding Information This work was supported by the National Institutes of Health [HL126638 to TPO] and American Heart Association [18POST3990251 to JRS].

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.

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.