Respiratory muscle work influences locomotor convective and diffusive oxygen transport in human heart failure during exercise.

INTRODUCTION: It remains unclear if naturally occurring respiratory muscle (RM) work influences leg diffusive O2 transport during exercise in heart failure patients with reduced ejection fraction (HFrEF). In this retrospective study, we hypothesized that RM unloading during submaximal exercise will lead to increases in locomotor muscle O2 diffusion capacity (DM O2 ) contributing to the greater leg VO2 . METHODS: Ten HFrEF patients and 10 healthy control matched participants performed two submaximal exercise bouts (i.e., with and without RM unloading). During exercise, leg blood flow was measured via constant infusion thermodilution. Intrathoracic pressure was measured via esophageal balloon. Radial arterial and femoral venous blood gases were measured and used to calculate leg arterial and venous content (CaO2 and CvO2 , respectively), VO2 , O2 delivery, and DM O2 . RESULTS: From CTL to RM unloading, leg VO2 , O2 delivery, and DM O2 were not different in healthy participants during submaximal exercise (all, p > .15). In HFrEF, leg VO2 (CTL: 0.7 ± 0.3 vs. RM unloading: 1.0 ± 0.4 L/min, p < .01), leg O2 delivery (CTL: 0.9 ± 0.4 vs. RM unloading: 1.4 ± 0.5 L/min, p < .01), and leg DM O2 (CTL: 31.5 ± 11.4 vs. RM unloading: 49.7 ± 18.6 ml min-1  mmHg-1 ) increased from CTL to RM unloading during submaximal exercise (all, p < .01), whereas CaO2 -CvO2 was not different (p = .51). The degree of RM unloading (i.e., % decrease in esophageal pressure-time integral during inspiration) was related to the % increase in leg DM O2 with RM unloading (r = -.76, p = .01). CONCLUSION: Our data suggest RM unloading leads to increased leg VO2 due to greater convective and diffusive O2 transport during submaximal exercise in HFrEF patients.

Combined influence of inspiratory loading and locomotor subsystolic cuff inflation on cardiovascular responses during submaximal exercise.

It is unknown if simultaneous stimulation of the respiratory and locomotor muscle afferents via inspiratory loading (IL) and locomotor subsystolic cuff inflation (CUFF) influences the cardiovascular responses during exercise. We hypothesized that combined IL and CUFF (IL + CUFF) will result in greater increases in blood pressure (MAP) and systemic vascular resistance (SVR) than IL and CUFF alone during exercise. Eight adults (6 males/2 females) were enrolled and performed four 10-min bouts of constant-load cycling eliciting 40% maximal oxygen uptake on a single day. For each exercise bout, the first 5 min consisted of spontaneous breathing. The second 5 min consisted of voluntary hyperventilation (i.e., breathing frequency of 40 breaths/min) with IL (30% maximum inspiratory pressure), CUFF (80 mmHg), IL + CUFF, or no intervention (CTL) in randomized order. During exercise, cardiac output and MAP were determined via open-circuit acetylene wash-in and manual sphygmomanometry, respectively, and SVR was calculated. Across CTL, IL, CUFF, and IL + CUFF, MAP was greater with each condition (CTL: 97 ± 14; IL: 106 ± 13; CUFF: 114 ± 14; IL + CUFF: 119 ± 15 mmHg, all P < 0.02). Furthermore, SVR was greater with IL + CUFF compared with IL, CUFF, and CTL (CTL: 6.6 ± 1.1; IL: 7.5 ± 1.4; CUFF: 7.5 ± 1.3; IL + CUFF: 8.2 ± 1.4 mmHg·L-1·min-1, all P < 0.02). Cardiac output was not different across conditions (CTL: 15.2 ± 3.8; IL: 14.8 ± 3.7; CUFF: 15.6 ± 3.5; IL + CUFF: 14.7 ± 4.3 L/min, all P > 0.05). These data demonstrate that simultaneous stimulation of respiratory and locomotor muscle afferent feedback results in additive MAP and SVR responses than IL and CUFF alone during submaximal exercise. These findings have important clinical implications for populations with exaggerated locomotor and respiratory muscle reflex feedbacks.NEW & NOTEWORTHY 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.

Predictors of exercise capacity following septal myectomy in patients with hypertrophic cardiomyopathy.

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.

Influence of Sex, Menstrual Cycle, and Menopause Status on the Exercise Pressor Reflex.

In this review, we highlight the underlying mechanisms responsible for the sex differences in the exercise pressor reflex (EPR), and, importantly, the impact of sex hormones and menopausal status. The EPR is attenuated in premenopausal women compared with age-matched men. Specifically, activation of the metaboreflex (a component of the EPR) results in attenuated increases in blood pressure and sympathetic vasomotor outflow compared with age-matched men. In addition, premenopausal women exhibit less transduction of sympathetic outflow to the peripheral vasculature than men. In stark contrast, postmenopausal women exhibit an augmented EPR arising from exaggerated metaboreflex-induced autonomic and cardiovascular reflexes. We propose that metaboreflex-induced autonomic and cardiovascular changes associated with menopause majorly contribute to the elevated blood pressure response during dynamic exercise in postmenopausal women. In addition, we discuss the potential mechanisms by which sex hormones in premenopausal women may impact the EPR as well as metaboreflex.