Key result
Remote ischaemic conditioning increased RR-interval by 40 ms, an effect that was prevented by brachial plexus block, demonstrating that intact afferent signaling is required to recruit the vagal anti-inflammatory reflex.
Why the study?
Non-invasive approaches in humans that may activate the vagal anti-inflammatory reflex are lacking.
Does remote ischaemic conditioning recruit vagal activity and activate the anti-inflammatory reflex in humans?
Does remote ischaemic conditioning recruit vagal activity and activate the anti-inflammatory reflex in humans?
Remote ischaemic conditioning recruits the vagal anti-inflammatory reflex, which requires intact afferent signalling from the peripheral tissue undergoing ischaemia/reperfusion to increase vagal tone and reduce neutrophil activation.
RIC may activate vagal anti-inflammatory pathways in humans; leaves open clinical translation pending randomized trials.
BACKGROUND Non-invasive approaches in humans that may activate the vagal anti-inflammatory reflex are lacking. Neurons within the dorsal motor vagal nucleus (DMVN) activate both the vagal anti-inflammatory reflex (which regulates leukocyte trafficking by controlling neutrophil surface CD11b expression) and cardioprotection afforded by remote ischemic conditioning (RIC). We tested the hypothesis that RIC recruits vagal activity and activates the anti-inflammatory reflex in humans by reducing neutrophil (CD16 + )CD11b expression. METHODS Participants (age:50±19 years; 53% female) underwent ultrasound-guided injection of local anaesthetic within the brachial plexus before applying 37×8 min cycles of brachial artery occlusion using a blood pressure cuff (RIC block ). RIC was repeated 6 weeks later without brachial plexus block. Masked analysers quantified vagal activity (heart rate variability) before, and 10 minutes after, the last RIC cycle. The primary outcome was RR-interval, compared between RIC block and RIC. Secondary outcomes were time-domain, frequency-domain, and flow cytometric quantification of CD16 + CD11b expression in whole blood (incubated with lipopolysaccharide (LPS) or saline) compared between RIC block and RIC. RESULTS RIC increased RR-interval (lowered heart rate) by 40ms (95% confidence intervals (95%CI):13-66; n=17; P =0.003). RR-interval did not change after RIC block (mean difference:20ms (95%CI:-11 to 50); P =0.19). High-frequency (vagal) modulation of heart rate was reduced after RIC block , but preserved after RIC ( P <0.001). indicating RIC preserved vagal activity. LPS-induced CD16 + CD11b + expression was lower after RIC (3615 median fluorescence units (95%CI:475-6754); P= 0.026), compared with 2331 units (95%CI:-3921 to 8582); P= 0.726) after RIC block . CONCLUSION RIC recruits the vagal anti-inflammatory reflex, which requires intact afferent signalling from the peripheral tissue undergoing ischaemia/reperfusion to increase vagal tone and reduce neutrophil activation. TRIAL REGISTRATION researchregistry6482.
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May et al. (2021) studied Elective upper limb surgery (n=17). Remote ischaemic conditioning (RIC) vs. RIC with brachial plexus block (RICblock) was evaluated on RR-interval (MD 40, 95% CI 13-66, p=0.003). Remote ischaemic conditioning increased RR-interval by 40 ms, an effect that was prevented by brachial plexus block, demonstrating that intact afferent signaling is required to recruit the vagal anti-inflammatory reflex.
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