A Comparative Investigation of the Pulmonary Vasodilating Effects of Inhaled NO Gas Therapy and Inhalation of a New Drug Formulation Containing a NO Donor Metabolite (SIN-1A).

Publication date: Jul 22, 2024

Numerous research projects focused on the management of acute pulmonary hypertension as Coronavirus Disease 2019 (COVID-19) might lead to hypoxia-induced pulmonary vasoconstriction related to acute respiratory distress syndrome. For that reason, inhalative therapeutic options have been the subject of several clinical trials. In this experimental study, we aimed to examine the hemodynamic impact of the inhalation of the SIN-1A formulation (N-nitroso-N-morpholino-amino-acetonitrile, the unstable active metabolite of molsidomine, stabilized by a cyclodextrin derivative) in a porcine model of acute pulmonary hypertension. Landrace pigs were divided into the following experimental groups: iNO (inhaled nitric oxide, n = 3), SIN-1A-5 (5 mg, n = 3), and SIN-1A-10 (10 mg, n = 3). Parallel insertion of a PiCCO system and a pulmonary artery catheter (Swan-Ganz) was performed for continuous hemodynamic monitoring. The impact of iNO (15 min) and SIN-1A inhalation (30 min) was investigated under physiologic conditions and U46619-induced acute pulmonary hypertension. Mean pulmonary arterial pressure (PAP) was reduced transiently by both substances. SIN-1A-10 had a comparable impact compared to iNO after U46619-induced pulmonary hypertension. PAP and PVR decreased significantly (changes in PAP: -30. 1% iNO, -22. 1% SIN-1A-5, -31. 2% SIN-1A-10). While iNO therapy did not alter the mean arterial pressure (MAP) and systemic vascular resistance (SVR), SIN-1A administration resulted in decreased MAP and SVR values. Consequently, the PVR/SVR ratio was markedly reduced in the iNO group, while SIN-1A did not alter this parameter. The pulmonary vasodilatory impact of inhaled SIN-1A was shown to be dose-dependent. A larger dose of SIN-1A (10 mg) resulted in decreased PAP and PVR in a similar manner to the gold standard iNO therapy. Inhalation of the nebulized solution of the new SIN-1A formulation (stabilized by a cyclodextrin derivative) might be a valuable, effective option where iNO therapy is not available due to dosing difficulties or availability.

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Concepts Keywords
Coronavirus acute pulmonary hypertension
Hemodynamic Administration, Inhalation
Pigs Animals
Therapy Disease Models, Animal
U46619 Hemodynamics
Hypertension, Pulmonary
inhalation therapy
linsidomine
Lung
Male
Molsidomine
Molsidomine
molsidomine active metabolite
Nitric Oxide
Nitric Oxide
Nitric Oxide Donors
Nitric Oxide Donors
Pulmonary Artery
pulmonary vasodilation
SIN-1A
Swine
Vasodilation
Vasodilator Agents
Vasodilator Agents

Semantics

Type Source Name
disease MESH pulmonary hypertension
disease MESH Coronavirus Disease 2019
disease MESH acute respiratory distress syndrome
drug DRUGBANK Molsidomine
drug DRUGBANK Inosine
drug DRUGBANK Nitric Oxide
disease VO dose
drug DRUGBANK Gold
disease VO effective
drug DRUGBANK Coenzyme M
disease MESH infection
disease MESH lung injury
disease MESH inflammation
disease MESH critically ill
drug DRUGBANK Etoperidone
disease VO inactivation
disease MESH methemoglobinemia
disease VO time
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Alpha-Linolenic Acid
drug DRUGBANK Isoniazid
disease IDO blood
disease MESH pathological processes
disease MESH thromboembolism
disease MESH edema
disease MESH pneumonia
disease IDO production
drug DRUGBANK Epoprostenol
drug DRUGBANK Iloprost
disease VO organ
disease MESH hypotension
drug DRUGBANK Indoleacetic acid
disease MESH syndrome
disease MESH dissociation
disease MESH hypertension
disease VO injection
drug DRUGBANK Ketamine
drug DRUGBANK Midazolam
drug DRUGBANK Propofol
disease VO vein
disease VO volume
disease VO frequency
drug DRUGBANK Oxygen
drug DRUGBANK Butorphanol
drug DRUGBANK Heparin
disease VO USA
disease VO protocol
drug DRUGBANK Ethanol
drug DRUGBANK Nitrogen
disease VO manufacturer
drug DRUGBANK Sodium Chloride
drug DRUGBANK Adenosine
drug DRUGBANK Arachidonic Acid
disease VO company
disease MESH pulmonary arterial hypertension
drug DRUGBANK Diethylstilbestrol
drug DRUGBANK Sildenafil
disease MESH Takayasu’s arteritis
drug DRUGBANK Oleic Acid
drug DRUGBANK Angiotensin II
drug DRUGBANK Aldosterone
disease MESH Disease Models Animal

Original Article

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