Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension
| Autor: | Xiao Qing Sun, Adenauer G. Casali, Nina Rol, Jolanda van der Velden, Marie-José Goumans, Diederik W. D. Kuster, Denielli da Silva Goncalves Bos, Christophe Guignabert, Robert Szulcek, Frances S. de Man, Ly Tu, Anton Vonk-Noordegraaf, M. Louis Handoko, Marc Humbert, Harm Jan Bogaard, Kondababu Kurakula, Paul J.M. Wijnker, Karina Rabello Casali, Cris dos Remedios, Cathelijne E. E. van der Bruggen, Peter Dorfmüller |
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| Přispěvatelé: | Physiology, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Heart failure & arrhythmias, APH - Quality of Care, APH - Personalized Medicine, Cardiology |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Hypertension Pulmonary Ventricular Dysfunction Right Receptor expression Pulmonary Artery Vascular Remodeling 030204 cardiovascular system & hematology Baroreflex Article Rats Sprague-Dawley 03 medical and health sciences Organ Culture Techniques 0302 clinical medicine Parasympathetic Nervous System Physiology (medical) Internal medicine Muscarinic acetylcholine receptor Heart rate medicine Animals Humans Cells Cultured Ejection fraction business.industry medicine.disease Pulmonary hypertension Rats Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Heart failure Ventricular Function Right Vascular resistance Cholinesterase Inhibitors Endothelium Vascular Cardiology and Cardiovascular Medicine business Pyridostigmine Bromide |
| Zdroj: | Da Silva Gonçalves Bós, D, Van Der Bruggen, C E E, Kurakula, K, Sun, X Q, Casali, K R, Casali, A G, Rol, N, Szulcek, R, Dos Remedios, C, Guignabert, C, Tu, L, Dorfmüller, P, Humbert, M, Wijnker, P J M, Kuster, D W D, Van Der Velden, J, Goumans, M J, Bogaard, H J, Vonk-Noordegraaf, A, De Man, F S & Handoko, M L 2018, ' Contribution of impaired parasympathetic activity to right ventricular dysfunction and pulmonary vascular remodeling in pulmonary arterial hypertension ', Circulation, vol. 137, no. 9, pp. 910-924 . https://doi.org/10.1161/CIRCULATIONAHA.117.027451 Circulation, 137(9), 910-924. Lippincott Williams and Wilkins |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.117.027451 |
| Popis: | Background: The beneficial effects of parasympathetic stimulation have been reported in left heart failure, but whether it would be beneficial for pulmonary arterial hypertension (PAH) remains to be explored. Here, we investigated the relationship between parasympathetic activity and right ventricular (RV) function in patients with PAH, and the potential therapeutic effects of pyridostigmine (PYR), an oral drug stimulating the parasympathetic activity through acetylcholinesterase inhibition, in experimental pulmonary hypertension (PH). Methods: Heart rate recovery after a maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity. RV ejection fraction was assessed in 112 patients with PAH. Expression of nicotinic (α-7 nicotinic acetylcholine receptor) and muscarinic (muscarinic acetylcholine type 2 receptor) receptors, and acetylcholinesterase activity were evaluated in RV (n=11) and lungs (n=7) from patients with PAH undergoing heart/lung transplantation and compared with tissue obtained from controls. In addition, we investigated the effects of PYR (40 mg/kg per day) in experimental PH. PH was induced in male rats by SU5416 (25 mg/kg subcutaneously) injection followed by 4 weeks of hypoxia. In a subgroup, sympathetic/parasympathetic modulation was assessed by power spectral analysis. At week 6, PH status was confirmed by echocardiography, and rats were randomly assigned to vehicle or treatment (both n=12). At the end of the study, echocardiography was repeated, with additional RV pressure-volume measurements, along with lung, RV histological, and protein analyses. Results: Patients with PAH with lower RV ejection fraction ( Conclusions: RV dysfunction is associated with reduced systemic parasympathetic activity in patients with PAH, with an inadequate adaptive response of the cholinergic system in the RV. Enhancing parasympathetic activity by PYR improved survival, RV function, and pulmonary vascular remodeling in experimental PH. |
| Databáze: | OpenAIRE |
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