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Clinical Investigations: PULMONARY HYPERTENSION |

Hemodynamic Effects of Sildenafil in Patients With Congestive Heart Failure and Pulmonary Hypertension*: Combined Administration With Inhaled Nitric Oxide

John J. Lepore, MD; Anjli Maroo, MD; Luca M. Bigatello, MD; G. William Dec, MD; Warren M. Zapol, MD; Kenneth D. Bloch, MD; Marc J. Semigran, MD
Author and Funding Information

Affiliations: *From the Cardiology Division (Drs. Lepore, Dec, and Semigran) and Cardiovascular Research Center (Dr. Bloch), Department of Medicine (Dr. Maroo), and Department of Anesthesia and Critical Care (Drs. Bigatello and Zapol), Massachusetts General Hospital, Harvard Medical School, Boston, MA.,  Currently at the Cardiovascular Medicine Division, Department of Medicine, University of Pennsylvania Health System, Philadelphia, PA.

Correspondence to: Marc J. Semigran, MD, Heart Failure and Cardiac Transplantation Unit, Massachusetts General Hospital, Bigelow 646, Boston, MA 02114; e-mail: semigran.marc@mgh.harvard.edu



Chest. 2005;127(5):1647-1653. doi:10.1378/chest.127.5.1647
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Study objectives: In patients with pulmonary hypertension (PH) secondary to congestive heart failure, inhaled nitric oxide (NO) increases pulmonary vascular smooth-muscle intracellular cyclic guanosine monophosphate (cGMP) concentration, thereby decreasing pulmonary vascular resistance (PVR) and increasing cardiac index (CI). However, these beneficial effects of inhaled NO are limited in magnitude and duration, at least in part due to cGMP hydrolysis by the type 5 isoform of phosphodiesterase (PDE5). The goal of this study was to determine the acute pulmonary and systemic hemodynamic effects of the selective PDE5 inhibitor, sildenafil, administered alone or in combination with inhaled NO in patients with congestive heart failure and PH.

Design: Single center, case series, pharmacohemodynamic study.

Setting: Cardiac catheterization laboratory of a tertiary care academic teaching hospital.

Patients: We studied 11 patients with left ventricular systolic dysfunction due to coronary artery disease or idiopathic dilated cardiomyopathy who had PH.

Interventions: We administered oral sildenafil (50 mg), inhaled NO (80 ppm), and the combination of sildenafil and inhaled NO during right-heart and micromanometer left-heart catheterization.

Measurements and results: Sildenafil administered alone decreased mean pulmonary artery pressure by 12 ± 5%, PVR by 12 ± 5%, systemic vascular resistance (SVR) by 13 ± 6%, and pulmonary capillary wedge pressure by 12 ± 7%, and increased CI by 14 ± 5% (all p < 0.05) [± SEM]. The combination of inhaled NO and sildenafil decreased PVR by 50 ± 4%, decreased SVR by 24 ± 3%, and increased CI by 30 ± 4% (all p < 0.01). These effects were greater than those observed with either agent alone (p < 0.05). In addition, sildenafil prolonged the pulmonary vasodilator effect of inhaled NO. Administration of sildenafil alone or in combination with inhaled NO did not change systemic arterial pressure or indexes of myocardial systolic or diastolic function.

Conclusions: PDE5 inhibition with sildenafil improves cardiac output by balanced pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled NO in patients with chronic congestive heart failure and PH.

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