Eliza Prodel

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

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.

Diving and Exercise: The interaction of trigeminal receptors and muscle metaboreceptors on muscle sympathetic nerve activity in humans

Swimming involves muscular activity and submersion, creating a conflict of autonomic reflexes elicited by the trigeminal receptors and skeletal muscle afferents. We sought to determine the autonomic cardiovascular responses to separate and concurrent stimulation of the trigeminal cutaneous receptors and metabolically sensitive skeletal muscle afferents (muscle metaboreflex). In eight healthy men (30 ± 2 yr) muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; Finometer), femoral artery blood flow (duplex Doppler ultrasonography), and femoral vascular conductance (femoral artery blood flow/MAP) were assessed during the following three experimental conditions: 1) facial cooling (trigeminal nerve stimulation), 2) postexercise ischemia (PEI; muscle metaboreflex activation) following isometric handgrip, and 3) trigeminal nerve stimulation with concurrent PEI. Trigeminal nerve stimulation produced significant increases in MSNA total activity (Δ347 ± 167%) and MAP (Δ21 ± 5%) and a reduction in femoral artery vascular conductance (Δ-17 ± 9%). PEI also evoked significant increases in MSNA total activity (Δ234 ± 83%) and MAP (Δ36 ± 4%) and a slight nonsignificant reduction in femoral artery vascular conductance (Δ-9 ± 12%). Trigeminal nerve stimulation with concurrent PEI evoked changes in MSNA total activity (Δ341 ± 96%), MAP (Δ39 ± 4%), and femoral artery vascular conductance (Δ-20 ± 9%) that were similar to those evoked by either separate trigeminal nerve stimulation or separate PEI. Thus, excitatory inputs from the trigeminal nerve and metabolically sensitive skeletal muscle afferents do not summate algebraically in eliciting a MSNA and cardiovascular response but rather exhibit synaptic occlusion, suggesting a high degree of convergent inputs on output neurons.

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, PetCO2 was either permitted to fluctuate spontaneously (control trial) or was clamped at 1 mmHg above resting levels (PetCO2 clamp 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 MCAvm were unchanged and MCACVCi decreased. However, in the PetCO2 clamp 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 ICACVC was unchanged. In the control trial, PEI decreased PetCO2 (Δ-7.0 ± 1.3 mmHg vs. rest), MCAvm and MCACVCi, whereas ICAQ and ICACVC were unchanged. In contrast, in the PetCO2 clamp trial both ICAQ (Δ18.5 ± 11.9 ml/min) and MCAvm (Δ8.8 ± 2.0 cm/s) were elevated, while ICACVC and MCACVCi were unchanged. In conclusion, when hyperventilation-related decreases in PetCO2 are prevented the activation of metabolically sensitive skeletal muscle afferent fibers increases cerebral blood flow.

Relationship between aortic augmentation index and blood pressure during metaboreflex activation in healthy young men.

BackgroundHeightened aortic augmentation index (AIx; surrogate of arterial stiffness) is associated with an elevated risk of cardiovascular events; however, it is currently unclear whether peripheral blood pressure (BP) modulates AIx. AimGiven this, we studied the relationship between AIx and BP under resting conditions as well as during skeletal muscle metaboreflex activation, which is a maneuver that generates steady elevations in BP. MethodsIn nine healthy male participants (23±2 years), the graded activation of the muscle metaboreflex was achieved by postexercise ischemia (PEI) following moderate and high-intensity static handgrip performed at 30 and 40% maximum voluntary contraction. Heart rate (ECG), arterial BP, and AIx (SphygmoCor) were measured. ResultsCompared with rest, mean arterial pressure was significantly increased during PEI30% (+24±4 mmHg, P<0.05 vs. rest) and was further augmented during PEI40% (+34±4 mmHg, P<0.05 vs. PEI30%). Similarly, AIx@HR75 increased significantly from rest during PEI30% (rest −9±3% vs. PEI30% +9±5%, P<0.05) and was further augmented during PEI40% (17±4%, P<0.05 vs. PEI30%). At rest, there was no relationship between AIx and BP. However, at PEI30%, there was a significant association between AIx and diastolic BP and mean arterial pressure (r=0.92, 0.87, respectively; P<0.05) and this association was maintained at PEI40% (r=0.94, 0.91, respectively; P<0.05). ConclusionsOur results indicate that acute elevations in peripheral BP are an important determinant of AIx during muscle metaboreflex activation in healthy men.

Sex differences in the contribution of blood pressure to acute changes in aortic augmentation index

Augmentation index (AIx), derived from aortic pulse waveform, is related to arterial stiffness and increased cardiac workload. Sex differences were observed in the relationship between blood pressure (BP) and AIx at rest. In addition, positive correlation between BP and AIx in men during a pressor stimulus was observed previously. However, whether BP is important to acute changes of AIx also in women is yet to be investigated. Therefore, we sought to investigate whether there are sex differences on the relationship between BP and AIx. In all, 16 men (age 27 ± 5 yr; height 176 ± 1 cm; weight 77 ± 7 kg; mean ± SD) and 13 women (age 26 ± 5 yr; height 164 ± 0.3 cm; weight 63 ± 7 kg; mean ± SD) underwent 3 min of rest followed by 3 min of cold pressor test (CPT). Heart rate during CPT was similar to rest. CPT increased BP in both groups and the magnitude was similar between groups. AIx and left ventricle energy wasted (EW) increased (men Δ13 ± 5% and women Δ17 ± 3%; p > 0.05 for group; men Δ580 ± 242 dynes cm−2 s−1 and women Δ618 ± 123 dynes cm−2 s−1; p > 0.05 for group) similarly in men and women during CPT. A positive Pearson correlation was found between AIx and BP in men (systolic BP (SBP) r = 0.77, p = 0.01; diastolic BP (DBP) r = 0.79, p = 0.01 and mean arterial pressure (MAP) r = 0.83, p < 0.01), however no correlation was seen in women (SBP r = 0.04, p = 0.89; DBP r = 0.24, p = 0.44 and MAP r = 0.23, p = 0.44). The contribution of BP to acute changes in AIx at higher levels of BP is different between men and women.

Cardiovascular response to trigeminal nerve stimulation at rest and during exercise in humans: does sex matter?

We sought to investigate the possibility that there are sex differences in the cardiovascular responses to trigeminal nerve stimulation (TGS) with cold exposure to the face at rest and during dynamic exercise. In 9 healthy men (age: 28 ± 3 yr; height: 178 ± 1 cm; weight: 77 ± 8 kg) and 13 women (age 26 ± 5 yr; height 164 ± 3 cm; weight 63 ± 7 kg) beat-to-beat heart rate (HR) and blood pressure were recorded. Mean arterial pressure (MAP), stroke volume (SV), cardiac index (CI), and total vascular resistance index (TVRI) were calculated. TGS was applied for 3 min at rest and in-between 10-min steady-state cycling exercise at a HR of 110 beats/min, the measurements were obtained during the last minute of each period. At rest, TGS increased MAP (men: Δ18 ± 8 mmHg; women: Δ23 ± 8 mmHg; means ± SD), TVRI (men: Δ1.1 ± 0.6 mmHg·l-1·min·m-2; women: Δ1.2 ± 1.2 mmHg·l-1·min·m-2) and SV (men: Δ19 ± 15 ml; women: Δ16 ± 11 ml) in both groups. CI increased with TGS in women but not in men. However, men presented a bradycardic response to TGS (Δ-11 ± 8 beats/min) that was not significant in women compared with baseline. Cycling exercise increased HR, MAP, SV, and CI and decreased TVRI in men and women. TGS during exercise further increased MAP in men and women and did not change CI in either group. SV and TVRI increased with TGS during exercise only in women. TGS during exercise evoked bradycardia in men (Δ-7 ± 9 beats/min), whereas HR was unchanged in women. Our findings indicate sex differences in TGS-related cardiovascular responses at rest and during exercise.