Effects of aging and coronary artery disease on sympathetic neural recruitment strategies during end-inspiratory and end-expiratory apnea

Abstract

In response to acute physiological stress, the sympathetic nervous system modifies neural outflow through increased firing frequency of lower-threshold axons, recruitment of latent subpopulations of higher-threshold axons, and/or acute modifications of synaptic delays. Aging and coronary artery disease (CAD) often modify efferent muscle sympathetic nerve activity (MSNA). Therefore, we investigated whether CAD (n = 14; 61 ± 10 yr) and/or healthy aging without CAD (OH; n = 14; 59 ± 9 yr) modified these recruitment strategies that normally are observed in young healthy (YH; n = 14; 25 ± 3 yr) individuals. MSNA (microneurography) was measured at baseline and during maximal voluntary end-inspiratory (EI) and end-expiratory (EE) apneas. Action potential (AP) patterns were studied using a novel AP analysis technique. AP frequency increased in all groups during both EI- and EE-apnea (all P < 0.05). The mean AP content per integrated burst increased during EI- and EE-apnea in YH (EI: Δ6 ± 4 APs/burst; EE: Δ10 ± 6 APs/burst; both P < 0.01) and OH (EI: Δ3 ± 3 APs/burst; EE: Δ4 ± 5 APs/burst; both P < 0.01), but not in CAD (EI: Δ1 ± 3 APs/burst; EE: Δ2 ± 3 APs/burst; both P = NS). When APs were binned into "clusters" according to peak-to-peak amplitude, total clusters increased during EI- and EE-apnea in YH (EI: Δ5 ± 2; EE: Δ6 ± 4; both P < 0.01), during EI-apnea only in OH (EI: Δ1 ± 2; P < 0.01; EE: Δ1 ± 2; P = NS), and neither apnea in CAD (EI: Δ -2 ± 2; EE: Δ -1 ± 2; both P = NS). In all groups, the AP cluster size-latency profile was shifted downwards for every corresponding cluster during EI- and EE-apnea (all P < 0.01). As such, inherent dysregulation exists within the central features of apnea-related sympathetic outflow in aging and CAD.

Fifty years of microneurography: learning the language of the peripheral sympathetic nervous system in humans

“…Thus, both approaches converge on the conclusion that low threshold axons observable under baseline conditions are recruited more frequently in at least some disease states. This pattern is different that than observed with ischemic heart disease with clinically normal ejection fraction where increases in baseline MSNA burst frequency occur but with little change in the number of APs per burst (Badrov et al 2016a). Therefore, the modified recruitment threshold of axons available under baseline conditions may be related to cardiac function and, by inference, cardiac sensory input to central autonomic control (Millar et al 2015).…”

“…In addition to, or perhaps because of, changes in baseline control outlined in the above paragraph, age and cardiovascular disorders may affect reflexive AP recruitment. Specifically, in contrast to similarly aged adults, patients with ischemic heart disease (but normal ejection fraction) expressed a near-absent ability to recruit larger APs during apneas of similar length (Badrov et al 2016a). Similarly, heart failure patients with reduced ejection fraction expressed diminished ability to increase the APs/burst despite the large stress imposed by a preventricular contraction (Maslov et al 2012), yet recruitment of new APs was normal.…”

“…Microneurography has become a fundamental tool in understanding sympathetic aberrations in several pathologies including congestive heart failure (Azevedo et al 2000), ischemic heart disease (Badrov et al 2016a;Malliani and Montano 2004), hypertension (Grassi 1998), Tako Tsubo disorder (Vaccaro et al 2014), sleep apnea (Floras 2016), and chronic kidney disease (Kaur et al 2017), as well as in obesity (Esler et al 2001;Lambert et al 2014), metabolic syndrome (Grassi 2006), and diabetes (Coats and Cruickshank 2014;Holwerda et al 2016). Agreeing with measures of circulating catecholamines and norepinephrine turnover (Esler 1995(Esler , 1997(Esler , 2001(Esler , 2003, baseline MSNA burst frequency tends to increase with age (Grassi et al 1995;Hogikyan and Supiano 1994;Iwase et al 1991) and particularly in heart failure with reduced ejection fraction (Floras 2009;Zucker et al 1995).…”

Hypoxic tachycardia is not a result of increased respiratory activity in healthy subjects

“…() breathed with nitrogen until decreased to ∼90%, then they held their breath for ∼5 s. Based on our experience, ∼10% reduction in rarely activates peripheral chemoreceptors and triggers a robust HVR in young, healthy subjects. Furthermore, voluntary end‐expiratory apnoea is known to be accompanied by various changes (hypoxia, hypercapnia, cessation of lung inflation and increased central drive to breath) that lead to marked sympathoexcitation, vasoconstriction, increase in blood pressure and slight increase in HR (Badrov, Lalande, Olver, Suskin, & Shoemaker, ; Patel, Heffernan, Ross, & Muller, ), and these effects are accentuated in hypoxic conditions (Leuenberger, Hardy, Herr, Gray, & Sinoway, ). In conclusion, it seems questionable whether the results by Eckberg et al.…”

Fine‐tuning our understanding of the baroreflex: size‐dependent regulation of action potential subpopulations

“…Indeed, this group has previously shown that older adults have a reduced ability to recruit previously silent AP subpopulations during sympathoexcitation (Badrov et al . 2016). The analysis of baroreflex gain within AP subpopulations may help to further elucidate mechanisms involved in exaggerated sympathoexcitation or declines in sympathetic baroreflex sensitivity with ageing.…”