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Sildenafil does not improve performance in 16.1 km cycle exercise time-trial in acute hypoxia.

ABSTRACT: Sildenafil is a pulmonary vasodilator that has potential to mitigate the decrement in endurance performance caused by hypoxic pulmonary vasoconstriction. The purpose of this study was to determine the effects of sildenafil on pulmonary artery pressure, cardiac output, pulse oxygen saturation, and exercise performance at moderate simulated altitude. We hypothesized that sildenafil would reduce the decline in exercise performance in hypoxia by blunting the rise in pulmonary artery pressure and causing a relative increase in cardiac output and oxygen saturation. Twelve endurance trained men performed three experimental cycling trials at sea level and simulated moderate altitude of 3,000m (FIO2 = 0.147) after ingesting either a placebo or sildenafil 50 mg capsule in a double blinded fashion. Each test consisted of a warmup period, a 15-minute steady state period at 60% of peak power output, and a 16.1 km time-trial. All subjects experienced a decline in maximal exercise capacity in hypoxia that ranged from 6% to 24%. This decline was correlated with the reduction in pulse oxygen saturation in hypoxic maximal exercise. Sildenafil had no effect on pulmonary artery pressure, cardiac output, or pulse oxygen saturation measured during steady state exercise. There was no effect of sildenafil on mean power output during the time-trial. During high intensity cycle exercise in acute, moderate hypoxia pulmonary artery pressure is unaffected by sildenafil and does not appear to influence cardiovascular function or exercise performance.

SUBMITTER: Carter EA

PROVIDER: S-EPMC6336365 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Sildenafil does not improve performance in 16.1 km cycle exercise time-trial in acute hypoxia.

Carter Eric A EA Sheel A William AW Milsom William K WK Koehle Michael S MS

PloS one 20190117 1

Sildenafil is a pulmonary vasodilator that has potential to mitigate the decrement in endurance performance caused by hypoxic pulmonary vasoconstriction. The purpose of this study was to determine the effects of sildenafil on pulmonary artery pressure, cardiac output, pulse oxygen saturation, and exercise performance at moderate simulated altitude. We hypothesized that sildenafil would reduce the decline in exercise performance in hypoxia by blunting the rise in pulmonary artery pressure and cau ...[more]

PMID: 30653578

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Project description:Introduction: Exercise performance is reproducible in experienced athletes; however, less trained participants exhibit greater variability in performance and pacing. To reduce variability, it is common practice to complete a familiarization prior to experimental testing. However, there are no clear guidelines for familiarizing novice participants to a cycling time-trial (TT), and research findings from novice populations may still be influenced by learning effects. Accordingly, the aims of this study were to establish the variability between TTs after administering differing familiarization protocols (duration or type) and to establish the number of familiarization trials required to limit variability over multiple trials. Methods: Thirty recreationally active participants, with no prior experience of a TT, performed a 20-km cycling TT on five separate occasions, after completing either a full (FF, 20-km TT, n = 10), a half (HF, 10-km TT, n = 10) or an equipment familiarization (EF, 5-min cycling, n = 10). Results: Variability of TT duration across five TTs was the lowest after completing FF (P = 0.69, η p2 = 0.05) compared to HF (P = 0.08, η p2 = 0.26) and EF (P = 0.07, η p2 = 0.21). In the FF group after TT2, the effect size for changes in TT duration was small (d < 0.49). There were large differences between later TTs in HF (d = 1.02, TT3-TT4) and EF (d = 1.12, TT4-TT5). The variability in mean power output profiles between trials was lowest within FF, with a similar pacing profile reproduced between TT3-TT5. Discussion: Familiarization of the exercise protocol influenced reproducibility of pacing and performance over multiple, maximal TTs, with best results obtained after a full experience of the exercise compared to HF and EF. The difference of TT1 to later TTs indicates that one familiarization is not adequate in reducing the variability of performance for novice participants. After the FF and an additional TT, performance changes between TTs were small, however, a reproducible pacing profile was not developed until after the FF and two additional TTs. These findings indicate that a minimum of three full familiarizations are necessary for novice participants to limit systematic error before experimental testing.

Project description:'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic environment. In lowlanders who ascend to altitude, genetic factors may also contribute to the substantial interindividual variation in exercise performance noted at altitude. We performed a systematic literature review to identify genetic variants of possible influence on human hypoxic exercise performance, commenting on the strength of any identified associations.All studies of the association of genetic factors with human hypoxic exercise performance, whether at sea level using 'nitrogen dilution of oxygen' (normobaric hypoxia), or at altitude or in low-pressure chambers (field or chamber hypobaric hypoxia, respectively) were sought for review.Two electronic databases were searched (Ovid MEDLINE, Embase) up to 31 January 2014. We also searched the reference lists of relevant articles for eligible studies. All studies published in English were included, as were studies in any language for which the abstract was available in English.Studies were selected and data extracted independently by two reviewers. Differences regarding study inclusion were resolved through discussion. The quality of each study was assessed using a scoring system based on published guidelines for conducting and reporting genetic association studies.A total of 11 studies met all inclusion criteria and were included in the review. Subject numbers ranged from 20 to 1,931 and consisted of healthy individuals in all cases. The maximum altitude of exposure ranged from 2,690 to 8,848 m. The exercise performance phenotypes assessed were mountaineering performance (n = 5), running performance (n = 2), and maximum oxygen consumption ([Formula: see text]O2max) (n = 4). In total, 13 genetic polymorphisms were studied, four of which were associated with hypoxic exercise performance. The adenosine monophosphate deaminase (AMPD1) C34T (rs17602729), beta2-adrenergic receptor (ADRB2) Gly16Arg single nucleotide polymorphism (SNP) (rs1042713), and androgen receptor CAG repeat polymorphisms were associated with altitude performance in one study, and the angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) (rs4646994) polymorphism was associated with performance in three studies. The median score achieved in the study quality analysis was 6 out of 10 for case-control studies, 8 out of 10 for cohort studies with a discrete outcome, 6 out of 9 for cohort studies with a continuous outcome, and 4.5 out of 8 for genetic admixture studies.The small number of articles identified in the current review and the limited number of polymorphisms studied in total highlights that the influence of genetic factors on exercise performance in hypoxia has not been studied in depth, which precludes firm conclusions being drawn. Support for the association between the ACE-I allele and improved high-altitude performance was the strongest, with three studies identifying a relationship. Analysis of study quality highlights the need for future studies in this field to improve the conduct and reporting of genetic association studies.

Project description:The primary objective of the current study was to determine the effect of moderate normobaric hypoxia exposure during constant load cycling on post-exercise energy metabolism recorded in normoxia. Indirect calorimetry was used to examine whole body substrate oxidation before, during, 40-60 min post, and 22 h after performing 60 min of cycling exercise at two different fractions of inspired oxygen (FIO2): (i) FIO2 = 0.2091 (normoxia) and (ii) FIO2 = 0.15 (hypoxia). Seven active healthy male participants (26 ± 4 years of age) completed both experimental trials in randomized order with a 7-day washout period to avoid carryover effects between conditions. Resting energy expenditure was initially elevated following cycling exercise in normoxia and hypoxia (Δ 0.14 ± 0.05, kcal min-1, p = 0.037; Δ 0.19 ± 0.03 kcal min-1, p < 0.001, respectively), but returned to baseline levels the next morning in both conditions. Although, the same absolute workload was used in both environmental conditions (157 ± 10 W), a shift in resting substrate oxidation occurred after exercise performed in hypoxia while post-exercise measurements were similar to baseline after cycling exercise in normoxia. The additional metabolic stress of hypoxia exposure was sufficient to increase the rate of lipid oxidation (Δ 42 ± 11 mg min-1, p = 0.019) and tended to suppress carbohydrate oxidation (Δ -55 ± 26 mg min-1, p = 0.076) 40-60 min post-exercise. This shift in substrate oxidation persisted the next morning, where lipid oxidation remained elevated (Δ 9 ± 3 mg min-1, p = 0.0357) and carbohydrate oxidation was suppressed (Δ -22 ± 6 mg min-1, p = 0.019). In conclusion, prior exercise performed under moderate normobaric hypoxia alters post-exercise energy metabolism. This is an important consideration when evaluating the metabolic consequences of hypoxia exposure during prolonged exercise, and future studies should evaluate its role in the beneficial effects of intermittent hypoxia training observed in persons with obesity and insulin resistance.

Dataset Information

Sildenafil does not improve performance in 16.1 km cycle exercise time-trial in acute hypoxia.

Publications

Sildenafil does not improve performance in 16.1 km cycle exercise time-trial in acute hypoxia.

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