A single inhaled dose of aviptadil (VIP) selectively dilated pulmonary blood vessels and reduced right heart strain in 20 pulmonary hypertension patients without side effects or systemic blood pressure drops.
Selective vasodilationInhaled aviptadil dilated pulmonary blood vessels without dropping systemic blood pressure — targeting therapy exactly where it's needed
What the researchers found
A single inhaled dose of aviptadil (100 μg), a synthetic form of vasoactive intestinal peptide (VIP), caused selective pulmonary vasodilation in patients with chronic pulmonary hypertension. The peptide improved stroke volume and mixed venous oxygen saturation — indicating reduced strain on the right ventricle — without affecting systemic blood pressure. Six of 20 patients (30%) achieved a clinically meaningful >20% reduction in pulmonary vascular resistance.
In patients with significant lung disease, aviptadil also tended to improve oxygenation. The effect was modest and temporary (as expected from a single dose), but no side effects were reported. The selective pulmonary vasodilation means the drug targeted the lung blood vessels specifically without dropping blood pressure throughout the rest of the body.
Why it matters
Pulmonary hypertension is a devastating condition where high pressure in the lung arteries forces the right side of the heart to work progressively harder until it fails. Current treatments help but don't cure the disease. VIP is naturally deficient in patients with idiopathic pulmonary arterial hypertension, making replacement therapy a logical approach. The fact that inhaled aviptadil selectively dilated lung vessels without systemic side effects is promising — inhaled delivery keeps the drug where it's needed most.
The numbers in context
n=20 · single 100 μg inhaled dose · 6/20 (30%) achieved >20% PVR reduction · improved stroke volume · improved mixed venous O2 saturation · no systemic BP drop · zero side effects
How the study worked
Open-label study in 20 patients with chronic pulmonary hypertension (9 PAH, 8 PH with lung disease, 3 chronic thromboembolic PH). During right-heart catheterization, patients inhaled a single 100 μg dose of aviptadil aerosol. Hemodynamic parameters (pulmonary vascular resistance, stroke volume, cardiac output) and blood gases (arterial and mixed venous oxygen saturation) were measured before and after inhalation.
Who was studied
20 patients with chronic pulmonary hypertension (9 PAH, 8 PH with lung disease, 3 chronic thromboembolic PH)
What this study cannot tell us
This was an uncontrolled, open-label study with no placebo group, so the effects could partly reflect the natural variability of hemodynamics during catheterization. The single-dose design only assessed acute effects — chronic dosing may produce different results. The 100 μg dose may have been suboptimal (the authors suggest higher doses should be tested). Only 20 patients were studied across three different PH subtypes, limiting subgroup analysis. The temporary nature of the effect means multiple daily doses would likely be needed for clinical use.
How to read the evidence
This is an uncontrolled, open-label study with 20 patients testing a single dose. While the hemodynamic measurements are objective (right-heart catheterization), the 'Preliminary' grade reflects the small size, lack of placebo control, and single-dose acute design.
When this study was published
Published in 2008, this was an early proof-of-concept study for inhaled VIP in pulmonary hypertension. Aviptadil has since been investigated further, including for COVID-19-related respiratory failure, though it has not yet become a standard PH treatment.
The bigger picture
Pulmonary hypertension treatment has advanced significantly with drugs like sildenafil, bosentan, and prostacyclin analogs, but many patients remain inadequately treated. VIP represents a different mechanism — replacing a peptide that is naturally deficient in PAH patients. The inhaled route is attractive because it concentrates the drug in the lungs and avoids systemic side effects. Aviptadil has since been investigated in other lung conditions including COVID-19-related respiratory failure.
Questions still open
- Would higher doses or chronic inhaled aviptadil treatment produce larger and sustained hemodynamic improvements?
- How does inhaled aviptadil compare to existing inhaled pulmonary vasodilators like iloprost or nitric oxide?
- Could VIP replacement therapy alter disease progression in idiopathic PAH, not just acutely improve hemodynamics?
Common questions
What is VIP and why is it relevant to pulmonary hypertension?
Why is 'selective pulmonary vasodilation' important?
Read the original research
Inhalation of vasoactive intestinal peptide in pulmonary hypertension.
The European respiratory journal, 32(5), 1289-94
Citation
Leuchte, H H; Baezner, C; Baumgartner, R A; Bevec, D; Bacher, G; Neurohr, C; Behr, J. (2008). Inhalation of vasoactive intestinal peptide in pulmonary hypertension.. The European respiratory journal, 32(5), 1289-94. https://doi.org/10.1183/09031936.00050008