Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle

© 2013 Rakobowchuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33610 yr) attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, lowflow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.161.0%, POST15:4.560.6%, POST30:5. 560.7% POST45:5.960.4%, p,0.01). Conversely, low-flow mediated constriction increased (PRE: 21.360.4%, POST15: 23.360.6%, POST30: 22.560.5% POST45: 21.560.12%, p,0.01). Reactive hyperaemia was reduced throughout recovery (p,0.05). Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.British Heart Foundation (PG/08/060/25340),a Physiological Society summer studentship to SG, and a Wellcome Trust Vacation Studentship to EP

Basal and distal occlusive brachial anterograde and retrograde shear rates.

<p>a) An increase in retrograde and a concomitant decrease in anterograde shear rate were evident upon distal arterial occlusion. This graph illustrates the mean of all vascular function responses. b) Basal and occlusive anterograde AUC shear was not altered by the prolonged low flow (PLF) (PRE vs. POST15, 30 or 45). Similarly c) basal and occlusive retrograde AUC shear were not altered by the PLF. Since menstrual cycle phase had no impact, mean responses are illustrated in graphs a and b. * Indicates a significant difference (<i>p</i>≤0.05) between basal and occlusive velocities. AUC is the area under the curve.</p

Basal and distal occlusive brachial artery shear.

<p>a–b) basal brachial mean blood velocity and brachial mean blood velocity measured when distal occlusion was applied was not altered by prolonged low flow (shaded area). c) Change in mean blood velocity upon cuff inflation was unaltered. MBV is the mean blood velocity.</p

Shear rate responses after cuff deflation.

<p>a) 60s brachial artery reactive hypaeremic shear rate area under the curve (AUC) were reduced throughout the recovery period compared with measures taken prior to the prolonged low flow (PLF) (shaded area). b) Peak reactive hyperaemic blood flow was unaltered by PLF whereas c) time to peak dilation was reduced at 15 minutes of recovery but recovered by 30 minutes. There were no significant differences within the menstrual cycle. * Indicates a significant difference (<i>p</i>≤0.05) from PRE PLF (main effect for Time) determined by post hoc analysis. AUC is the area under the curve.</p

Vascular function alterations.

<p>a) Relative flow mediated dilation (FMD) was reduced after low flow induced vascular dysfunction (PLF) (shaded area) and remained suppressed throughout recovery although it was not different from PRE at 30 and 45 minutes. b) Diameter prior to each vascular function test was unchanged compared with PRE while c) maximal diameter was blunted and as a result d) absolute FMD was reduced at 15 minutes after PLF. e) Conversely L-FMC was augmented at 15 minutes after PLF but recovered by 30 minutes. f) As a result of augmented L-FMC and reduced FMD, TVR was unaltered throughout the protocol. No significant differences were noted within the menstrual cycle. * Indicates a significant main effect for time (<i>p</i>≤0.05) from specifically difference compared to PRE PLF (post hoc comparison). FMD is flow-mediated dilation, L-FMC is low flow mediated constriction, and TVR is total vascular reactivity.</p

Schematic representation of a testing session timeline.

<p>Participants arrived at the laboratory and rested supine for 20 minutes prior to a brachial artery vascular function assessment (VF test). A ten-minute recovery period was immediately followed by prolonged low flow (PLF 20 min) and subsequent VF tests were completed at 15, 30 and 45 minutes into recovery. A venous blood sample was obtained at 120minutes (↓). The VF test mean blood velocity (MBV) measurements are highlighted in the expansion. Basal MBV was measured prior to cuff inflation; occlusive MBV 30s prior to cuff deflation; and hyperaemic MBV was measured continuously for 90s after cuff release as illustrated.</p