Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease.

Abstract

BACKGROUND:

Hemodynamic assessment during exercise may unmask an impaired functional reserve of the right ventricle and the pulmonary vasculature in patients with connective tissue disease. We assessed the effect of intravenous sildenafil on the hemodynamic response to exercise in patients with connective tissue disease.

METHODS:

In this proof-of-concept study, patients with connective tissue disease and mean pulmonary arterial pressure (mPAP) >20 mm Hg were subjected to a supine exercise hemodynamic evaluation before and after administration of intravenous sildenafil 10 mg.

RESULTS:

Ten patients (four with moderately elevated mPAP 21-24 mm Hg; six with mPAP >25 mm Hg) underwent hemodynamic assessment. All of them showed markedly abnormal exercise hemodynamics. Intravenous sildenafil was well tolerated and had significant hemodynamic effects at rest and during exercise, although without pulmonary selectivity. Sildenafil reduced median total pulmonary resistance during exercise from 6.22 (IQR 4.61-8.54) to 5.24 (3.95-6.96) mm Hg·min·L-1 (p = 0.005) and increased median pulmonary arterial capacitance during exercise from 1.59 (0.93-2.28) to 1.74 (1.12-2.69) mL/mm Hg (p = 0.005).

CONCLUSIONS:

In patients with connective tissue disease who have an abnormal hemodynamic response to exercise, intravenous sildenafil improved adaption of the right ventricular-pulmonary vascular unit to exercise independent of resting mPAP. The impact of acute pharmacological interventions on exercise hemodynamics in patients with pulmonary vascular disease warrants further investigation.

TRIAL REGISTRATION:

Clinicaltrials.gov NCT01889966.

• Authors: Andreas J Rieth, Manuel J Richter, Alexander Berkowitsch, Marc Frerix, Ingo H Tarner, Veselin Mitrovic, Christian W Hamm
• Journal: PloS one (PLoS One) Vol. 13 Issue 9 Pg. e0203947 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 30235235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vasodilator Agents
• Sildenafil Citrate

Topics

• Aged
• Arterial Pressure (drug effects, physiology)
• Connective Tissue Diseases (physiopathology)
• Exercise (physiology)
• Exercise Test
• Female
• Hemodynamics (drug effects, physiology)
• Humans
• Injections, Intravenous
• Male
• Middle Aged
• Sildenafil Citrate (administration & dosage)
• Vasodilator Agents (administration & dosage)