Phosphodiesterase inhibition restores hypoxia-induced cerebrovascular dysfunction subsequent to improved systemic redox homeostasis: A randomized, double-blind, placebo-controlled crossover study

Figures

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  Figure 1.. Study design. The study adopted a randomized, double-blind, placebo-controlled crossover design. All participants completed two trials (sildenafil and placebo) and were exposed to both normoxia (FiO2 = 0.21) and normobaric hypoxia (FiO2 = 0.14) during both visits. Participants were administered either 50 mg (oral) sildenafil or 50 mg placebo which was followed by a 50 min resting period in normoxia before data collection (blood sample, cardiopulmonary and cerebrovascular assessments). Participants were then exposed to hypoxia for 60 min. A second tablet of either 50 mg sildenafil or 50 mg placebo was then administered followed by another 50 min rest period prior to a second bout of data collection. Each trial was separated by a 7-day recovery period.

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  Figure 2.. Basal metrics of systemic oxidative-nitrosative stress (OXNOS). (a) plasma ascorbate free radical (A•−); (b) total plasma nitric oxide (NO) concentration (nitrite + S-Nitrosothiols); (c) total red blood cell (RBC) NO (nitrite + S-Nitrosohemoglobin +hemoglobin-bound NO); and (d) total (plasma + total RBC) NO concentrations; AU, arbitrary units; Values are mean ± SD. n = 12 for all parameters.

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  Figure 3.. Transfer function analysis of the cerebral pressure–flow relationship during spontaneous oscillations in mean arterial blood pressure (MAP) and middle cerebral artery velocity (MCAv). (a) low frequency (LF) Coherence; (b) LF Gain; (c) LF Phase; (d) very low frequency (VLF) Coherence; (e) VLF Gain and (f) VLF Phase; AU, arbitrary units; Values are mean ± SD. n = 12 for LF parameters, whereas n = 8 for VLF data.

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  Figure 4.. Cerebrovascular reactivity to carbon dioxide (CVRCO2). (a) cerebrovascular reactivity to hypercapnia (CVRCO2Hyper); (b) cerebrovascular reactivity to hypocapnia (CVRCO2Hypo) and (c) cerebrovascular reactivity to carbon dioxide range (CVRCO2Range); Values are mean ± SD. n = 12 for all parameters.