Influence of the Metaboreflex on Pulmonary Vascular Capacitance in Heart Failure

Abstract

Purpose An impaired metaboreflex is associated with abnormal ventilatory and peripheral vascular function in heart failure (HF), whereas its influence on cardiac function or pulmonary vascular pressure remain unclear. We aimed to assess whether metabolite-sensitive neural feedback (metaboreflex) from locomotor muscles via post-exercise regional circulatory occlusion (RCO) attenuates pulmonary vascular capacitance (GXCAP) and/or circulatory power (CircP) in HF patients. Methods Eleven HF patients (NYHA class: I/II; ages, 51±15; ejection fraction: 32±9%) and 11 age and gender matched controls (ages, 43±9) completed three cycling sessions (four-minutes, 60% peak oxygen uptake [VO2]). Session one: control trial=normal recovery (NR). Sessions two or three: bilateral upper-thigh pressure tourniquets inflated suprasystolic at end-exercise (RCO) for 2-minute recovery with or without inspired CO2 (RCO+CO2) (randomized). Mean arterial pressure (MAP), heart rate, and VO2 were continuously measured. Estimates of central hemodynamics; CircP=(VO2×MAP)/weight, oxygen pulse index (O2pulseI=(VO2/heart rate)/body surface area), and GXCAP=O2pulseI×end-tidal partial pressure CO2 were calculated. Results At rest and end-exercise, CircP and GXCAP were lower in HF versus controls (P<0.05), with no differences between transients (P>0.05). At 2-minute recovery, GXCAP was lower during RCO versus NR in both groups (72±23 versus 98±20 and 73±34 versus 114±35 mL·beat−1·mm Hg·m−2, respectively; P<0.05); whereas, CircP did not differ between transients (P>0.05). Differences (% and Δ) between baseline and 2-minute recovery amongst transients suggest the metaboreflex attenuates GXCAP in HF. Differences (% and Δ) between baseline and 2-min recovery amongst transients suggest the metaboreflex may attenuate CircP in controls. Conclusion The present observations suggest locomotor muscle metaboreflex activation may influence CircP in controls but not in HF. However, metaboreflex activation may evoke decreases in GXCAP (increased pulmonary vascular pressures) in HF and controls.

Clinical safety of blood flow-restricted training? A comprehensive review of altered muscle metaboreflex in cardiovascular disease during ischemic exercise

“…Irrespective of augmented or blunted sympathetic responses to metaboreflex activation, most studies show a preserved BP increase to metaboreflex activation in HF (12,27,122,132). However, as previously reported in animal studies, HF individuals have an impaired capacity to increase SV and CO H95 during metaboreflex activation; thus the metaboreflex-mediated BP increase is largely dependent upon an increase in SVR (12,27,122,132,165). Accentuated peripheral vasoconstriction occurs in nonactive vascular beds (122) and in active muscle (3), with the latter reducing skeletal muscle perfusion during exercise, thereby increasing fatigue-related symptoms and stimulating further metaboreflex responses.…”

“…HF patients also suffer with exertional dyspnea, which might be related to changes in pulmonary vascular dynamics (83,165), which is an important mediator of exercise intolerance in this population (31). Importantly, activation of the metaboreflex may promote pulmonary vasoconstriction (83,165) and abnormal ventilatory responses during exercise in HF (122,123,126,144,145). Piepoli et al (122) reported increased ventilatory responses during PEMI after leg cycling exercise in patients with HF.…”

V̇o2 kinetics associated with moderate-intensity exercise in heart failure: impact of intrathecal fentanyl inhibition of group III/IV locomotor muscle afferents

“…In contrast, but while still physiologically linked to peripheral-central hemodynamic maldistribution, noteworthy discussions spanning across study lines of slowed V O 2 kinetics (both pulmonary and muscle) to abnormal activation of group III/IV afferents commonly implicate the milieu of the blood biochemical intramuscular environment (20,(22)(23)(24)50) as a key factor preceding the cascade of events leading to exercise intolerance in HF (1,28,31,37,39,42). For example, it has been suggested by Scott et al (39,40), Crisafulli et al (11), our group (31,44), and others (1,35) that skeletal muscle phenotypes, particularly those associated with provoking recruitment of nonoxidative energetic demands (leading to, e.g., increased H ϩ , increased P i /phosphocreatine, and increased La Ϫ ) prime an intramuscular environment ideal for group III/IV afferent activation, resulting in exercise intolerance secondary to augmented SVR, blood pressure, and ventilation in HF. Likewise, there are well-established parallels between prolonged V O 2 kinetics and increased O 2 def coinciding with skeletal muscle characteristics that include unfavorable contributions from 1 type IIb fiber (glycolytic) recruitment/proportion, increased H ϩ , and increased P i /phosphocreatine in potentially explaining the predisposition for exercise intolerance in HF (5,7,18,25,28,36,37,42).…”

Contemporary Strategies to Manage High Blood Pressure in Patients with Coexistent Resistant Hypertension and Heart Failure With Reduced Ejection Fraction

“…This is a scientific area requiring directed efforts focusing on both mechanistic and patient-oriented clinical research, possibly centering on afferent pathways involving exercise-induced neuromuscular signaling changes. Examples of such phenomena have been frequently tested and observed in HFrEF [30,31,[37][38][39][40][41][42][43]. In this context, many cases of refractory hypertension are suggested to be the result of excess and dysregulated sympathetic tone [6].…”