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© 2020 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation Background: Atrial fibrillation (AF) and hypertension are independently associated with impaired autonomic function determined using heart rate variability (HRV). As these conditions frequently co-exist, we sought to determine whether AF would worsen HRV in hypertensive patients. Design: We studied HRV in AF (and hypertension) (n = 61) and hypertension control group (n = 33). The AF (and hypertension) group was subdivided into permanent AF (n = 30) and paroxysmal AF (n = 31) and re-studied. Time-domain, frequency-domain and nonlinear measures of HRV were determined. Permanent AF group (n = 30) was followed up after 8 weeks following optimisation of their heart rate and blood pressure (BP). Results: Time-domain and nonlinear indices of HRV were higher in AF (and hypertension) group compared to hypertensive controls (P ≤.01). Time-domain and nonlinear indices of HRV were higher in permanent AF group compared to paroxysmal AF (P ≤.001). Permanent AF was an independent predictor of HRV on multivariable analysis (P =.006). Optimisation of heart rate and BP had no significant impact on HRV in permanent AF. Conclusions: AF, independent of hypertension, is characterised with marked HRV and is possibly related to vagal tone. HRV is higher in permanent AF compared to paroxysmal AF suggesting evident autonomic influence in the pathophysiology of permanent AF. Modulation of autonomic influence on cardiovascular system should be explored in future studies.

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Atrial fibrillation (AF) and hypertension often co-exist and both are associated with endothelial dysfunction. We hypothesised that AF would further worsen endothelium-dependent flow-mediated dilatation (FMD) in hypertension patients compared to those without AF. In a cross-sectional comparison, we measured brachial artery diameter at rest and during reactive hyperaemia following 5 min of arterial occlusion in two patient groups: AF (and hypertension) (n = 61) and hypertension control groups (n = 33). The AF (and hypertension) subgroups: permanent AF (n = 30) and paroxysmal AF (n = 31) were also assessed. The permanent AF patients received heart rate and blood pressure (BP) control optimisation and were then followed up after eight weeks for repeat FMD testing. There was no significant difference in FMD between AF (and hypertension) group and hypertension control group (4.6%, 95% CI [2.6–5.9%] vs 2.6%, 95% CI [1.9–5.3%]; p = 0.25). There was a significant difference in FMD between permanent AF and paroxysmal AF groups (3.1%, 95% CI [2.3–4.8%] vs 5.9%, 95% CI [4.0–8.1%]; p = 0.02). Endothelium-dependent FMD response showed a non-significant improvement trend following eight weeks of heart rate and BP optimisation (3.1%, 95% CI [2.3–4.8%] (baseline) vs 5.2%, 95% CI [3.9–6.5%] (follow up), p = 0.09). Presence of AF generally does not incrementally worsen endothelial dysfunction in hypertension patients, although the duration and frequency of AF (paroxysmal AF to permanent AF) does lead to worsening endothelial function. Eight weeks of BP optimisation did not significantly improve endothelial dysfunction as measured by FMD.

© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society New Findings: What is the central question of this study? Does facial cooling-mediated stimulation of cutaneous trigeminal afferents associated with the diving response increase cerebral blood flow or are factors associated with breath-holding (e.g. arterial carbon dioxide accumulation, pressor response) more important in humans? What is the main finding and its importance? Physiological factors associated with breath-holding such as arterial carbon dioxide accumulation and the pressor response, but not facial cooling (trigeminal nerve stimulation), make the predominant contribution to diving response-mediated increases in cerebral blood flow in humans. Abstract: Diving evokes a pattern of physiological responses purported to preserve oxygenated blood delivery to vital organs such as the brain. We sought to uncouple the effects of trigeminal nerve stimulation on cerebral blood flow (CBF) from other modifiers associated with the diving response, such as apnoea and changes in arterial carbon dioxide tension. Thirty-seven young healthy individuals participated in separate trials of facial cooling (FC, 3 min) and cold pressor test (CPT, 3 min) under poikilocapnic (Protocol 1) and isocapnic conditions (Protocol 2), facial cooling while either performing a breath-hold (FC +BH) or breathing spontaneously for a matched duration (FC −BH) (Protocol 3), and BH during facial cooling (BH +FC) or without facial cooling (BH −FC) (Protocol 4). Under poikilocapnic conditions neither facial cooling nor CPT evoked a change in middle cerebral artery blood flow velocity (MCA vmean; transcranial Doppler) (P > 0.05 vs. baseline). Under isocapnic conditions, facial cooling did not change MCA vmean (P > 0.05), whereas CPT increased MCA vmean by 13% (P < 0.05). Facial cooling with a concurrent BH markedly increased MCA vmean (Δ23%) and internal carotid artery blood flow (ICAQ; duplex Doppler ultrasound) (Δ26%) (P

Copyright © 2020 the American Physiological Society South Asians living in the United Kingdom have a 1.5-fold greater risk of ischemic stroke than the general population. Impaired cerebrovascular carbon dioxide (CO2) reactivity is an independent predictor of ischemic stroke and cardiovascular mortality. We sought to test the hypothesis that cerebrovascular CO2 reactivity is reduced in South Asians. Middle cerebral artery blood velocity (MCA Vm) was measured at rest and during stepwise changes in end-tidal partial pressure of CO2 (PETCO2) in South Asian (n = 16) and Caucasian European (n = 18) men who were young (~20 yr), healthy, and living in the United Kingdom. Incremental hypercapnia was delivered via the open-circuit steady-state method, with stages of 4 and 7% CO2 (~21% oxygen, nitrogen balanced). Cerebrovascular CO2 reactivity was calculated as the change in MCA Vm relative to the change in PETCO2. MCA Vm was not different in South Asians [59 (9) cm/s, mean (standard deviation)] and Caucasian Europeans [61 (12) cm/s; P > 0.05]. Similarly, cerebrovascular CO2 reactivity was not different between the groups [South Asian 2.53 (0.76) vs. Caucasian European 2.61 (0.81) cm·s-1·mmHg-1; P > 0.05]. Brachial artery flow-mediated dilation was lower in South Asians [5.48 (2.94)%] compared with Caucasian Europeans [7.41 (2.28)%; P < 0.05]; however, when corrected for shear rate no between-group differences in flow-mediated dilation were observed (P > 0.05). Flow-mediated dilation was not correlated with cerebrovascular CO2 reactivity measures. In summary, cerebrovascular CO2 reactivity and flow-mediated dilation corrected for shear rate are preserved in young healthy South Asian men living in the United Kingdom. NEW & NOTEWORTHY Previous reports have identified an increased risk of ischemic stroke and peripheral endothelial dysfunction in South Asians compared with Caucasian Europeans. The main finding of this study is that cerebrovascular carbon dioxide reactivity (an ind

© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. The role of prostaglandins (PGs) in exercise hyperemia is controversial. We tested their contributions in moderate intensity forearm exercise, whether their release is oxygen (O2)-dependent or affected by aging. A total of 12 young (21 ± 1 years) and 11 older (66 ± 2 years) recreationally active men performed rhythmic and isometric handgrip contractions at 60% maximum voluntary contraction for 3 min during air breathing after placebo, after cyclooxygenase (COX) inhibition with aspirin, while breathing 40% O2 and during their combination (aspirin + 40% O2). Forearm blood flow (FBF) was recorded with venous occlusion plethysmography (forearm vascular conductance (FVC): FBF/mean arterial pressure). Venous efflux of PGI2 and PGE2 were assessed by immunoassay. Postcontraction increases in FVC were similar for rhythmic and isometric contractions in young and older men, and accompanied by similar increases in efflux of PGI2 and PGE2. Aspirin attenuated the efflux of PGI2 by 75%–85%, PGE2 by 50%–70%, (p <.05 within group; p >.05 young versus. older), and postcontraction increases in FVC by 22%–27% and 17%–21% in young and older men, respectively (p <.05 within group and young versus. older). In both age groups, 40% O2 and aspirin + 40% O2 caused similar inhibition of the increases in FVC and efflux of PGs as aspirin alone (p <.05 within group). These results indicate that PGs make substantial contributions to the postcontraction hyperemia of rhythmic and isometric contractions at moderate intensities in recreationally active young and older men. Given PGI2 is mainly released by endothelium and PGE2 by muscle fibers, we propose PG generation is dependent on the contraction-induced falls in O2 at these sites.

© Copyright © 2020 Junejo, Lip and Fisher. It is now well established that besides being the most common sustained arrhythmia, atrial fibrillation (AF) is a major healthcare burden. Risk of debilitating stroke is increased in AF patients, but even in the absence of stroke, this population is at heightened risk of cognitive decline, depression, and dementia. The reasons for this are complex, multifactorial, and incompletely understood. One potential contributing mechanism is cerebrovascular dysfunction. Cerebral blood flow is regulated by chemical, metabolic, autoregulatory, neurogenic, and systemic factors. The dysfunction in one or more of these mechanisms may contribute to the elevated risk of cognitive decline and cerebrovascular events in AF. This short review presents the evidence for diminished cerebral blood flow, cerebrovascular carbon dioxide reactivity (i.e., cerebrovascular vasodilatory reserve), cerebral autoregulation, and neurovascular coupling in AF patients when compared to control participants in sinus rhythm. Further work is needed to understand the physiological mechanisms underpinning these observations and their clinical significance in atrial fibrillation patients.

© The Author(s) 2019. The risk of cognitive decline and stroke is increased by atrial fibrillation (AF). We sought to determine whether neurovascular coupling and cerebral autoregulation are blunted in people with AF in comparison with age-matched, patients with hypertension and healthy controls. Neurovascular coupling was assessed using five cycles of visual stimulation for 30 s followed by 30 s with both eyes-closed. Cerebral autoregulation was examined using a sit–stand test, and a repeated squat-to-stand (0.1 Hz) manoeuvre with transfer function analysis of mean arterial pressure (MAP; input) and middle cerebral artery mean blood flow velocity (MCA Vm; output) relationships at 0.1 Hz. Visual stimulation increased posterior cerebral artery conductance, but the magnitude of the response was blunted in patients with AF (18 [8] %; mean [SD]) and hypertension (17 [8] %), in comparison with healthy controls (26 [9] %) (P < 0.05). In contrast, transmission of MAP to MCA Vm was greater in AF patients compared to hypertension and healthy controls, indicating diminished cerebral autoregulation. We have shown for the first time that AF patients have impaired neurovascular coupling responses to visual stimulation and diminished cerebral autoregulation. Such deficits in cerebrovascular regulation may contribute to the increased risk of cerebral dysfunction in people with AF.

© 2019, The Author(s). Purpose: We tested whether the values of limb blood flow calculated with strain-gauge venous occlusion plethysmography (VOP) differ when venous occlusion is achieved by automated, or manual inflation, so providing rapid and slower inflation, respectively. Method: In 9 subjects (20–30 years), we calculated forearm blood flows (FBF) values at rest and following isometric handgrip at 70% maximum voluntary contraction (MVC) when rapid, or slower inflation was used. Result: Rapid and slower cuff inflation took 0.23 ± 0.01 (mean ± SEM) and 0.92 ± 0.02 s, respectively, reflecting the range reported in published studies. At rest, FBF calculated from the 1st cardiac cycle after rapid and slower inflation gave similar values: 10.5 ± 1.4 vs. 9.6 ± 1.3 ml dl − 1 min − 1 , respectively (P > 0.05). However, immediately post-contraction, FBF was ~ 40% lower with slower inflation: 54.6 ± 5.1 vs. 33.8 ± 4.2 ml dl − 1 min − 1 (P < 0.01). The latter value was similar to that calculated over the 3rd cardiac cycle following rapid inflation: 2nd cardiac cycle: 40.5 ± 4.5; 3rd cycle: 32.6 ± 4.5 ml dl − 1 min − 1 . Regression analyses of FBFs recorded at intervals post-contraction showed those calculated over the 1st, 2nd, or 3rd cardiac cycles with rapid inflation correlated well with those from the 1st cardiac cycle with manual inflation (r = 0.79, 0.82, 0.79; P < 0.01). However, only the slope for the 3rd cycle with rapid inflation vs. slower inflation was close to unity (2.07, 1.34, and 0.94, respectively). Conclusion: These findings confirm that the 1st cardiac cycle following venous occlusion should be used when calculating FBF using VOP and, but importantly, indicate that cuff inflation should be almost instantaneous; just ≥ 0.9 s leads to substantial underestimation, especially at high flows.

© 2018, The Author(s). Purpose: Prevalence of cardiovascular disease (CVD) is greater in South Asians (SAs) than White Europeans (WEs). Endothelial dysfunction and blunted forearm vasodilatation to environmental stressors have been implicated in CVD. We investigated whether these features are present in young SA men. Methods: In 15 SA and 16 WE men (19–23 years), we compared changes in forearm blood flow, arterial blood pressure (ABP), forearm vascular conductance (FVC), heart rate, and electrodermal resistance (EDR; sweating) following release of arterial occlusion (reactive hyperaemia endothelium-dependent) and 5 single sounds at 5–10 min intervals (stressors). Results: All were normotensive. Peak reactive hyperaemia was smaller in SAs than WEs (FVC increase: 0.36 ± 0.038 vs 0.44 ± 0.038 units; P < 0.05). Furthermore, in WEs, mean FVC increased at 5, 15, and 20 s of each sound (vasodilatation), but increased at 5 s only in SAs, decreasing by 20 s (vasoconstriction). This reflected a smaller proportion of SAs showing forearm vasodilatation at 15 s (5/15 SAs vs 11/16 WEs: P < 0.01), the remainder showing vasoconstriction. Concomitantly, WEs showed greater bradycardia and EDR changes. Intra-class correlation analyses showed that all responses were highly reproducible over five sounds in both WEs and SAs. Moreover, sound-evoked changes in ABP and FVC were negatively correlated in each ethnicity (P < 0.01). However, WEs showed preponderance of forearm vasodilatation and depressor responses; SAs showed preponderance of vasoconstriction and pressor responses. Conclusions: Endothelium-dependent vasodilatation is blunted in young SA men. This could explain their impaired forearm vasodilatation and greater pressor responses to repeated environmental stressors, so predisposing SAs to hypertension and CVD.