***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Sildenafil causes pulmonary vasodilation , thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude . The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise . We hypothesized that 1 ) sildenafil would have no significant effects on normoxic exercise , and 2 ) sildenafil would improve cardiac output , arterial oxygen saturation ( SaO2 ) , and performance during hypoxic exercise . Ten trained men performed one practice and three experimental trials at sea level ( SL ) and simulated high altitude ( HA ) of 3,874 m. Each cycling test consisted of a set-work-rate portion ( 55 % work capacity : 1 h SL , 30 min HA ) followed immediately by a time trial ( 10 km SL , 6 km HA ) . Double-blinded capsules ( placebo , 50 , or 100 mg ) were taken 1 h before exercise in a r and omly counterbalanced order . For HA , subjects also began breathing hypoxic gas ( 12.8 % oxygen ) 1 h before exercise . At SL , sildenafil had no effects on any cardiovascular or performance measures . At HA , sildenafil increased stroke volume ( measured by impedance cardiography ) , cardiac output , and SaO2 during set-work-rate exercise .  Sildenafil lowered 6-km time-trial time by 15 % ( P<0.05 ) . SaO2 was also higher during the time trial ( P<0.05 ) in response to sildenafil , despite higher work rates . Post hoc analyses revealed two subject groups , sildenafil responders and nonresponders , who improved time-trial performance by 39 % ( P<0.05 ) and 1.0 % , respectively . No dose-response effects were observed . During cycling exercise in acute hypoxia , sildenafil can greatly improve cardiovascular function , SaO2 , and performance for certain individuals Background —Sildenafil citrate is an effective and widely prescribed therapy for erectile dysfunction . Little is known about the effects of sildenafil on neural control of the circulation or about the effects of sildenafil on neurocirculatory stress responses . Methods and Results —We studied 14 normal volunteers ( age 32±7 years ) who were r and omized in a double-blind crossover fashion to receive a single oral dose of sildenafil 100 mg or placebo  on 2 separate study days . Blood pressure , heart rate , forearm vascular resistance , muscle sympathetic nerve activity , and plasma catecholamines were measured at baseline and at 30 and 60 minutes after sildenafil and after placebo administration . The effects of sildenafil and placebo on neural and circulatory responses to stressful stimuli ( sustained h and grip , maximal forearm ischemia , mental stress , and the cold pressor test ) were also evaluated . Blood pressure , heart rate , and forearm vascular resistance  after sildenafil and placebo were similar . However , muscle sympathetic nerve activity increased strikingly after sildenafil ( by 141±26 % , mean±SEM ) compared with placebo ( 3±8 % ) ( P = 0.006 ) ; plasma norepinephrine levels also increased by 31±5 % after sildenafil administration ( P = 0.004 ) . Sympathetic nerve traffic during mental , physical , and cold stresses was 2- to 8-fold higher after sildenafil than with placebo ( P < 0.05 ) . Conclusions —Sildenafil causes a marked increase in sympathetic activation , evident both at rest and during stressful stimuli . Sympathetic activation  by sildenafil may have implication s for underst and ing cardiovascular events associated with sildenafil use UNLABELLED Sildenafil improves maximal exercise capacity at high altitudes ( ∼4350 - 5800 m ) by reducing pulmonary arterial pressure and enhancing oxygen delivery , but the effects on exercise performance at less severe altitudes are less clear . PURPOSE To determine the effects of sildenafil on cardiovascular hemodynamics ( heart rate , stroke volume , and cardiac output ) , arterial oxygen saturation ( SaO2 ) , and 6-km time-trial performance of endurance-trained men and women at a simulated altitude of ∼3900 m. METHODS Twenty men and 15 women , endurance-trained , completed one experimental exercise trial ( 30 min at 55 % of altitude-specific capacity + 6-km time trial ) at sea level ( SL ) and two trials at simulated high altitude ( HA ) while breathing hypoxic gas ( 12.8 % FIo2 ) after ingestion of either placebo or 50 mg sildenafil in double-blind , r and omized , and counterbalanced fashion . RESULTS Maximal exercise capacity and SaO2 were significantly reduced at HA compared to SL ( 18%-23 % ) , but sildenafil did not significantly improve cardiovascular hemodynamics or time-trial performance in either men or women compared to placebo and only improved SaO2 in women ( 4 % ) . One male subject ( 5 % of male subjects , 2.8 % of all subjects ) exhibited a meaningful 36-s improvement in time-trial performance  with sildenafil compared to placebo . CONCLUSIONS In this group of endurance trained men and women  , sildenafil had very little influence on cardiovascular hemodynamics , SaO2 , and 6-km time-trial performance at a simulated altitude of ∼3900 m. It appears that a very small percentage of endurance-trained men and women derive meaningful improvements in aerobic performance from sildenafil at a simulated altitude of ∼3900 Sildenafil improves oxygen delivery and maximal exercise capacity at very high altitudes ( ≥4,350 m ) , but it is unknown whether sildenafil improves these variables and longer- duration exercise performance at moderate and high altitudes where competitions are more common . The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics , arterial oxygen saturation ( SaO2 ) , peak exercise capacity ( Wpeak ) , and 15-km time trial performance in endurance-trained subjects at simulated moderate ( MA ; ~2,100 m , 16.2 % FIO2 ) and high ( HA ; ~3,900 m , 12.8 % FIO2 ) altitudes . Eleven men and ten women completed two HA Wpeak trials after ingesting placebo or 50 mg sildenafil . Subjects then completed four exercise trials ( 30 min at 55 % of altitude-specific Wpeak + 15-km time trial ) at MA and HA after ingesting placebo or 50 mg sildenafil . All trials were performed in r and omized , counterbalanced , and double-blind fashion . Sildenafil had little influence on cardiovascular hemodynamics at MA or HA , but did result in higher SaO2 values ( + 3 % , p < 0.05 ) compared to placebo during steady state and time trial exercise at HA . Wpeak at HA was 19 % lower than SL ( p < 0.001 ) and was not significantly affected by sildenafil . Similarly , the significantly slower time trial performance at MA ( 28.1 ± 0.5 min , p = 0.016 ) and HA ( 30.3 ± 0.6 min , p < 0.001 ) compared to SL ( 27.5 ± 0.6 min ) was unaffected by sildenafil . We conclude that sildenafil is unlikely to exert beneficial effects at altitudes < 4,000 m for a majority of the population We sought to determine the influence of sildenafil on the diffusing capacity of the lungs for carbon monoxide ( DLCO ) and the components of DLCO ( pulmonary capillary blood volume Vc , and alveolar – capillary membrane conductance DM ) at rest and following exercise with normoxia and hypoxia . This double-blind placebo-controlled , cross-over study included 14 healthy subjects ( age = 33 ± 11 years , ht = 181 ± 8 cm , weight = 85 ± 14 kg , BMI = 26 ± 3 kg/m2 , peak normoxic VO2 = 36 ± 6 ml/kg , mean ± SD ) . Subjects were r and omized to placebo or 100 mg sildenafil 1 h prior to entering a hypoxic tent with an FiO2 of 12.5 % for 90 min . DLCO , Vc , and DM were assessed at rest , every 3 min during exercise , at peak exercise , and 10 and 30 min post exercise . Sildenafil attenuated the elevation in PAP at rest and during recovery with exposure to hypoxia , but pulmonary arterial pressure immediately post exercise was not different between sildenafil and placebo . Systemic O2 saturation and VO2peak did not differ between the two conditions . DLCO was not different between groups at any time point . VC was higher with exercise in the placebo group , and the difference in DM between sildenafil and placebo was significant only when corrected for changes in Vc ( DM/Vc = 0.57 ± 0.29 vs. 0.41 ± 0.16 , P = 0.04 ) . These results suggest no effect of sildenafil on DLCO , but an improvement in DM when corrected for changes in Vc during short-term hypoxic exposure with exercise OBJECTIVE Hypobaric hypoxia decreases exercise capacity and causes hypoxic pulmonary vasoconstriction and pulmonary hypertension . The phosphodiesterase-5 inhibitor sildenafil is a pulmonary vasodilator that may improve exercise capacity at altitude . We aim ed to determine whether sildenafil improves exercise capacity , measured as maximal oxygen consumption ( peak V̇o2 ) , at moderate altitude in adults 60 years or older . METHODS The design was a r and omized , double-blind , placebo-controlled , crossover study . After baseline cardiopulmonary exercise testing at 1400 m , 12 healthy participants ( 4 women ) aged 60 years or older , who reside permanently at approximately 1400 m and are regularly active in self-propelled mountain recreation above 2000 m , performed maximal cardiopulmonary cycle exercise tests in a hypobaric chamber at a simulated altitude of 2750 m after ingesting sildenafil and after ingesting a placebo . RESULTS After placebo , mean peak V̇o2 was significantly lower at 2750 m than 1400 m : 37.0 mL · kg(-1 ) · min(-1 ) ( 95 % CI , 32.7 to 41.3 ) vs 39.1 mL · kg(-1 ) · min(-1 ) ( 95 % CI , 33.5 to 44.7 ; P = .020 ) . After placebo , there was no difference in heart rate ( HR ) or maximal workload at either altitude ( z = 0.182 ; P = .668 , respectively ) . There was no difference between sildenafil and placebo at 2750 m in peak V̇o2 ( P = .668 ) , O2 pulse ( P = .476 ) , cardiac index ( P = .143 ) , stroke volume index ( z = 0.108 ) , HR ( z = 0.919 ) , or maximal workload ( P = .773 ) . Transthoracic echocardiography immediately after peak exercise at 2750 m showed tricuspid annular plane systolic velocity was significantly higher after sildenafil than after placebo ( P = .019 ) , but showed no difference in tricuspid annular plane systolic excursion ( P = .720 ) . CONCLUSIONS Sildenafil ( 50 mg ) did not improve exercise capacity in adults 60 years or older at moderate altitude in our study . This might be explained by a " dosing effect " or insufficiently high altitude Context Alveolar hypoxia causes pulmonary hypertension .  Sildenafil causes pulmonary vasodilatation in patients subjected to acute hypoxia at sea level . These observations have generated hypotheses about using sildenafil in acute mountain sickness and for treating pulmonary hypertension in patients with chronic respiratory insufficiency . Contribution Sildenafil reduced hypoxic pulmonary hypertension at rest and with exercise and increased maximum exercise capacity and cardiac output in 14 mountain climbers who received sildenafil and placebo in r and om order at low altitude while breathing hypoxic gas and again at an elevation of 5400 m. Caution s The results of this small study are preliminary . Sildenafil 's role in the management of acute mountain sickness is unclear . The Editors Acute and chronic hypoxia are well-characterized causes of pulmonary hypertension ( 1 , 2 ) . Exercise capacity is reduced during severe alveolar hypoxia , regardless of whether the condition is due to environmental factors such as high altitude or to various respiratory diseases . The extent to which hemodynamic constraints related to enhanced right ventricular afterload contribute to limited exercise capacity during hypoxia and pulmonary hypertension remains unknown . High-altitude pulmonary edema and acute mountain sickness are serious complications that can occur during ascent to high altitudes . Individual susceptibility plays a major role in development of these conditions ( 3 , 4 ) , and the association of high-altitude pulmonary edema with an exaggerated pulmonary hypertensive response to hypoxia and increased vascular leakage is well documented ( 5 , 6 ) . Several factors are thought to cause hypo 
    Output:
    
Results Sildenafil showed a large effect for decreasing PAP during exercise and at rest , a small effect for increasing CO during exercise and a moderate effect at rest , a moderate effect for increasing SPO2 and a small effect for improving performance .
In a subgroup analysis , there was no statistically significant difference between 100 and 50 mg sildenafil dose on SPO2 .
Sildenafil had a moderate effect on increasing SPO2 and performance at terrestrial hypobaric altitude but only a small effect on both in normobaric hypoxia .
Regression analysis showed that hypoxic dose ( PO2 ) and metabolic rate do not account for a significant portion of the variance in effect size for sildenafil on PAP , CO , SPO2 and performance .
Conclusion This meta- analysis indicates that sildenafil reduces PAP , has a moderate to small effect on CO and SPO2 , and no effect on performance