BackgroundExercise capacity has been shown to predict quality of life, mortality, and risk for hospitalization in patients with Cystic Fibrosis (CF). Many patients with CF exhibit exercise intolerance, the mechanism of which has yet to be elucidated. Sildenafil, a phosphodiesterase type 5 inhibitor, increases blood flow and therefore may improve exercise capacity in patients with CF.PurposeThe purpose of this study was to determine whether an acute dose of sildenafil improves exercise capacity in patients with CF.Methods13 patients with CF (mean age = 25 ± 10 years) participated in a double blind, randomized, placebo controlled study. Exercise capacity utilizing the Godfrey Protocol on a cycle ergometer was assessed at baseline and 1 hour following treatment with either sildenafil (50 mg) or placebo.ResultsA significantly greater increase (p = 0.024) in VO2 peak was observed following sildenafil treatment (4.16 ± 1.54 ml/kg/FFM) compared to placebo (1.09 ± 1.31 ml/kg/FFM). The change in maximal heart rate during exercise was statistically (p = 0.007) greater following sildenafil treatment (6.07 ± 4.04 bpm) compared to placebo (−1.54 ± 6.06 bpm). The change in chronotropic index (CRI) was significantly (p = 0.006) higher following sildenafil treatment (0.08 ± 0.02) compared with placebo (0.04 ± 0.02).Conclusion/InterpretationThese findings suggest that an acute dose of sildenafil improves exercise capacity in patients with CF. In addition, treatment with sildenafil improved CRI. Future studies should focus on elucidating the mechanisms for improvement in exercise capacity and CRI as both are predictors of mortality.Support or Funding InformationSupported in part by the Medical College of Georgia's Medical Scholar Program and the Laboratory of Integrative Vascular and Exercise Physiology.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

INTRODUCTION: The anticoagulation and antiplatelet strategies of patients with high-risk ST-elevation myocardial infarction (STEMI) can be a difficult balance of risk, especially for those that require an intra-aortic balloon pump (IABP). The incidence of major bleeding in patients that require GP IIb/IIIa inhibitors and heparin is 8.3% compared to 4.9% in those treated with bivalirudin alone; however, the latter are at increased risk of in-stent thrombosis. While the guidelines support GP IIb/IIIa inhibitors in high-risk situations and heparin for IABP, these therapies further increase bleeding risk. To illustrate these management difficulties, we present a high-risk STEMI complicated by fatal pulmonary hemorrhage.