Dyspnea in Eisenmenger syndrome and its amelioration by sildenafil: role of J receptors.

Abstract

BACKGROUND:

In Eisenmenger syndrome (ES), oral phosphodiesterase type-5 inhibitors, which are preferential pulmonary vasodilators, reduce the elevated pulmonary artery pressure and pulmonary vascular resistance index by increasing cyclic guanosine monophosphate (cGMP). However, no information is available as to how pulmonary vasodilatation alleviates the accompanying dyspnoea and improves patient's exercising ability.

OBJECTIVES:

As the natural stimulus of juxtapulmonary capillary (J) receptors is an increase in interstitial pressure, the aim was to estimate their threshold level stimulation chemically by intravenous lobeline, before and after 6 weeks of sildenafil therapy in treatment-naive ES patients.

METHODS:

Nine Eisenmenger syndrome patients [mean age=26 (SD=1.6) years] underwent 6MWT and an exercise test before and 6 weeks after oral sildenafil (20mg 3× D). Their respiratory responses to threshold doses of intravenous lobeline were determined at both these stages.

RESULTS:

After 6 weeks of sildenafil therapy, the 6MWD [from 453.3 (SD=50.9) m to 516.6 (SD=48.9) m; P=0.001] and the duration of exercise with the modified Bruce protocol from 7 min 53 s (SD=0.04) to 10 min 44 s (SD=0.88) (P=0.001) improved significantly. However, the improvement in oxygen saturation was not noteworthy. The lobeline dose required to produce threshold level of respiratory effects was higher in ES patients [37.5 (SD=3.4) μg/kg] and with sildenafil therapy it fell significantly [20.6 (SD=1.8) μg/kg; P=0.001].

CONCLUSIONS:

J receptor threshold doses were elevated in ES patients and fell significantly with sildenafil therapy that was associated with improved exercise tolerance, implying thereby a role of J receptors in producing dyspnea in ES patients.

• Authors: Ashima Anand, Niraj Srivastava, Parag Barwad, Sivasubramanian Ramakrishnan, Ambuj Roy, Balram Bhargava
• Journal: International journal of cardiology (Int J Cardiol) Vol. 174 Issue 3 Pg. 574-8 (Jul 01 2014) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 24820738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Piperazines
• Purines
• Sulfones
• Vasodilator Agents
• Sildenafil Citrate

Topics

• Adult
• Dyspnea (diagnosis, drug therapy, physiopathology)
• Eisenmenger Complex (diagnosis, drug therapy, physiopathology)
• Exercise Test (methods)
• Female
• Humans
• Male
• Piperazines (pharmacology, therapeutic use)
• Purines (pharmacology, therapeutic use)
• Sensory Receptor Cells (drug effects, physiology)
• Sildenafil Citrate
• Sulfones (pharmacology, therapeutic use)
• Vasodilator Agents (pharmacology, therapeutic use)