Baroreflex resetting of human sympathetic action potential subpopulations during exercise.

This study tested the hypothesis that during fatiguing volitional exercise in humans, descending cortical signals and ascending skeletal muscle metaboreflex signals exert divergent control over baroreflex resetting of sympathetic action potential (AP) discharge. We quantified the baroreflex gain for sympathetic AP clusters within the muscle sympathetic nerve activity neurogram (peroneal microneurography and continuous wavelet transform) during baseline (BSL), the first 2-min of a 5-min isometric handgrip (20% of maximal effort; IHG1), the last 2-min of IHG (IHG2), and during postexercise circulatory occlusion (PECO) in seven healthy participants. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability (%) versus diastolic blood pressure (DBP; mmHg) for 10 normalized AP clusters.

Normal and excessive muscle sympathetic nerve activity in heart failure: implications for future trials of therapeutic autonomic modulation.

Aims: Patients with sympathetic excess are those most likely to benefit from novel interventions targeting the autonomic nervous system. To inform such personalized therapy, we identified determinants of augmented muscle sympathetic nerve activity (MSNA) in heart failure, versus healthy controls.

Methods And Results: We compared data acquired in 177 conventionally-treated, stable non-diabetic patients in sinus rhythm, aged 18-79 years (149 males; 28 females; left ventricular ejection fraction [LVEF] 25 ± 11% [mean ± standard deviation]; range 5-60%), and, concurrently, under similar conditions, in 658 healthy, normotensive volunteers (398 males; aged 18-81 years).

Muscle Sympathetic Excitatory Response to Dynamic 1-Leg Cycling in Heart Failure With Preserved Ejection Fraction.

We provide the first description in a patient with heart failure with preserved ejection fraction of the "paradoxical," exaggerated reflex increase in muscle sympathetic nerve activity in the opposite, stationary limb during dynamic 1-leg cycling exercise that was documented previously in patients with reduced ejection fraction. ().

Influence of sex and age on the relationship between aerobic fitness and muscle sympathetic nerve activity in healthy adults.

We examined the influence of sex and age on the relationship between aerobic fitness and muscle sympathetic nerve activity (MSNA) in healthy adults. Data were assessed from 224 volunteers (88 females), aged 18-76 yr, in whom resting MSNA (microneurography) and peak oxygen uptake (V̇o; incremental exercise test) were evaluated. When separated into younger (<50 yr) and older (≥50 yr) subgroups, there were inverse relationships between relative V̇o (mL·kg·min) and MSNA burst frequency in younger males ( = 0.

Imaging Insulin Granule Dynamics in Human Pancreatic β-Cells Using Total Internal Reflection Fluorescence (TIRF) Microscopy.

Due to the ultra-thin optical sectioning capability of exclusively illuminating space at the interface where total internal reflection occurs, the TIRF microscope has been indispensable for monitoring biological processes adjacent to the plasma membrane with excellent signal-to-noise ratio. Insulin-containing granules fuse with the plasma membrane to release contents within hundreds of milliseconds, which involves well-orchestrated assembly of SNARE complex and associated proteins. A video-rate multiple-color TIRF microscope offers the unique opportunity to visualize single secretory granule docking and fusion dynamics and can also map its regulators with high spatiotemporal resolution.

NOD2/CARD15 gene mutation is not associated with susceptibility to Wegener's granulomatosis.

Objective: Polymorphisms and mutations in the NOD2/CARD15 gene have been reported to increase susceptibility to Crohn's disease (CD) and the rare Blau syndrome, respectively. Both conditions are characterized by granuloma formation. We assessed the influence of variants in the CARD15 gene in another disorder characterized by granuloma, Wegener's granulomatosis (WG).