Development of a human model for the study of effects of hypoxia, exercise, and sildenafil on cardiac and vascular function in chronic heart failure

Damy, T. et al. (2015) Development of a human model for the study of effects of hypoxia, exercise, and sildenafil on cardiac and vascular function in chronic heart failure. Journal of Cardiovascular Pharmacology, 66(3), pp. 229-238. (doi: 10.1097/FJC.0000000000000262) (PMID:25874853)

Abstract

Background: Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects. Methods and Results: In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (-1 ± 2%; P = 0.043), systemic vascular resistance (-87 ± 156 dyn·s-1·cm-2; P = 0.034), and RVTG (-2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P < 0.001) and RVTG (19 ± 11 mm Hg; P < 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by hypoxia. The rise in RVTG with exercise was not substantially reduced by sildenafil. Conclusions: Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation–perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cleland, Professor John
• Authors: Damy, T., Hobkirk, J., Walters, M., Ciobanu, A., Rigby, A. S., Kallvikbacka-Bennett, A., Guellich, A., Dubois-Randé, J.-L., Hittinger, L., Clark, A. L., and Cleland, J. G.F.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Journal of Cardiovascular Pharmacology
• Publisher: Lippincott, Williams & Wilkins
• ISSN: 0160-2446
• ISSN (Online): 1533-4023