Muscle metaboreflex and cerebral blood flow regulation in humans:implications for exercise with blood flow restriction

We investigated the effect of activating metabolically sensitive skeletal muscle afferents (muscle metaboreflex) on cerebral blood flow and the potentially confounding influence of concomitant changes in the partial pressure of arterial carbon dioxide. Eleven healthy males (25 ± 4 yr) performed submaximal leg cycling exercise on a semirecumbent cycle ergometer (heart rate: ∼120 beats/min), and assessments were made of the partial pressure of end-tidal carbon dioxide (PetCO2), internal carotid artery blood flow (ICAQ) and conductance (ICACVC), and middle cerebral artery mean blood velocity (MCAvm) and conductance index (MCACVCi).The muscle metaboreflex was activated during cycling with leg blood flow restriction (BFR) or isolated with postexercise ischemia (PEI). In separate trials, PetCO2was either permitted to fluctuate spontaneously (control trial) or was clamped at 1 mmHg above resting levels (PetCO2clamp trial). In the control trial, leg cycling with BFR decreased PetCO2(Δ−4.8 ± 0.9 mmHg vs. leg cycling exercise) secondary to hyperventilation, while ICAQ, ICACVC, and MCAvmwere unchanged and MCACVCidecreased. However, in the PetCO2clamp trial, leg cycling with BFR increased both MCAvm(Δ5.9 ± 1.4 cm/s) and ICAQ(Δ20.0 ± 7.8 ml/min) and attenuated the decrease in MCACVCi, while ICACVCwas unchanged. In the control trial, PEI decreased PetCO2(Δ−7.0 ± 1.3 mmHg vs. rest), MCAvmand MCACVCi, whereas ICAQand ICACVCwere unchanged. In contrast, in the PetCO2clamp trial both ICAQ(Δ18.5 ± 11.9 ml/min) and MCAvm(Δ8.8 ± 2.0 cm/s) were elevated, while ICACVCand MCACVCiwere unchanged. In conclusion, when hyperventilation-related decreases in PetCO2are prevented the activation of metabolically sensitive skeletal muscle afferent fibers increases cerebral blood flow.</jats:p

Supplementary Material for: Effects of Moderate Hyperbilirubinemia on Nutritive Swallowing and Swallowing-Breathing Coordination in Preterm Lambs

<b><i>Background:</i></b> Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. HB induces acute neurological disorders (somnolence, abnormal tone, feeding difficulties, auditory dysfunction) and alterations in respiratory control. These findings suggest brainstem neurotoxicity that could also affect swallowing centers. <b><i>Objective:</i></b> To test the hypothesis that HB impairs nutritive swallowing (NS) and swallowing-breathing coordination. <b><i>Methods:</i></b> Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. On day 5 of life (D0), moderate HB (150-250 µmol/l) was induced during 17 h in the HB group. Swallowing was assessed via recording of pharyngeal pressure and respiration by respiratory inductance plethysmography and pulse oximetry. The effect of HB on NS was assessed during standardized bottle-feeding. A second recording was performed 48 h after recovery from HB (D3). <b><i>Results:</i></b> Swallows were less frequent (p = 0.003) and of smaller volume (p = 0.01) in HB lambs while swallowing frequency was decreased (p = 0.004). These differences disappeared after HB normalization. Swallowing-breathing coordination was impaired in HB lambs, with a decrease in percent time with NS burst-related apneas/hypopneas at D0 and D3. Simultaneously, HB lambs tended to experience more severe desaturations (<80%) during bottle-feeding. Finally, following bottle-feeding, the respiratory rate was significantly lower, along with an increased apnea duration in HB lambs. <b><i>Conclusions:</i></b> Swallowing and swallowing-breathing coordination are altered by acute moderate HB in preterm lambs. Decreased efficiency at bottle-feeding is accompanied by continuation of breathing during swallow bursts, which may promote lung aspiration

Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

KEY POINTS: The increase in blood pressure observed during physical activities is exaggerated in patients with hypertension, exposing them to a higher cardiovascular risk. Neural signals from the skeletal muscles appear to be overactive, resulting in this abnormal response in hypertensive patients. In the present study, we tested whether the attenuation of these neural signals in hypertensive patients could normalize their abnormal increase in blood pressure during physical activity. Attenuation of the neural signals from the leg muscles with intrathecal fentanyl injection reduced the blood pressure of hypertensive men during cycling exercise to a level comparable to that of normotensive men. Skeletal muscle afferent overactivity causes the abnormal cardiovascular response to exercise and was reverted in this experimental model, appearing as potential target for treatment. ABSTRACT: Hypertensive patients present an exaggerated increase in blood pressure and an elevated cardiovascular risk during exercise. Although controversial, human studies suggest that group III and IV skeletal muscle afferents might contribute to this abnormal response. In the present study, we investigated whether attenuation of the group III and IV muscle afferent signal of hypertensive men eliminates the exaggerated increase in blood pressure occurring during exercise. Eight hypertensive men performed two sessions of 5 min of cycling exercise at 40 W. Between sessions, the subjects were provided with a lumbar intrathecal injection of fentanyl, a μ‐opioid receptor agonist, aiming to attenuate the central projection of opioid‐sensitive group III and IV muscle afferent nerves. The cardiovascular response to exercise of these subjects was compared with that of six normotensive men. During cycling, the hypertensive group demonstrated an exaggerated increase in blood pressure compared to the normotensive group (mean ± SEM: +17 ± 3 vs. +8 ± 1 mmHg, respectively; P < 0.05), whereas the increase in heart rate, stroke volume, cardiac output and vascular conductance was similar (P > 0.05). Fentanyl inhibited the blood pressure response to exercise in the hypertensive group (+11 ± 2 mmHg) to a level comparable to that of the normotensive group (P > 0.05). Moreover, fentanyl increased the responses of vascular conductance and stroke volume to exercise (P < 0.05), whereas the heart rate response was attenuated (P < 0.05) and the cardiac output response was maintained (P > 0.05). The results of the present study show that attenuation of the exercise pressor reflex normalizes the blood pressure response to cycling exercise in hypertensive individuals

BRIEF ISOCAPNIC HYPEROXIA INCREASES SYMPATHETIC VASCULAR TRANSDUCTION DURING SYMPATHOEXCITATORY MANEUVERS IN HEALTHY HUMANS

Sao Paulo Research Foundation (FAPESP)National Counsel of Technological and Scientific Development (CNPq)Research Support Foundation of the State of Rio de Janeiro (FAPERJ)Univ Fed Sao Paulo, Dept Physiol, Sao Paulo, SP, BrazilFluminense Fed Univ, Dept Physiol & Pharmacol, Niteroi, RJ, BrazilUniv Brasilia, Fac Phys Educ, Brasilia, DF, BrazilUniv Fed Sao Paulo, Dept Physiol, Sao Paulo, SP, BrazilWeb of Scienc