Supra-coronary aortic banding improves right ventricular function in experimental pulmonary arterial hypertension in rats by increasing systolic right coronary artery perfusion.
coronary artery
microvascular rarefaction
mitochondrial metabolism
monocrotaline
pyruvate dehydrogenase kinase
single-photon emission computed tomography (SPECT)
Journal
Acta physiologica (Oxford, England)
ISSN: 1748-1716
Titre abrégé: Acta Physiol (Oxf)
Pays: England
ID NLM: 101262545
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
09
01
2020
revised:
20
04
2020
accepted:
21
04
2020
pubmed:
28
4
2020
medline:
27
7
2021
entrez:
28
4
2020
Statut:
ppublish
Résumé
Pulmonary arterial hypertension (PAH) results in right ventricular (RV) dysfunction owing, in part, to RV ischemia. The relative contribution of RV microvascular rarefaction vs reduced right coronary artery perfusion pressure (RCA-PP) to RV ischemia remains unknown. We hypothesize that increasing RCA-PP improves RV function in PAH by increasing RV systolic perfusion. Supra-coronary aortic banding (SAB) or sham surgery was performed on male Sprague-Dawley rats. Seven to ten days later, rats received either monocrotaline (MCT; 60 mg/kg) or saline. After 1 month, echocardiography, cardiac catheterization, Supra-coronary aortic banding increased systolic pressures in proximal aorta and systolic RCA-PP in SAB + MCT vs MCT rats (114 ± 12 vs 5 ± 9 mm Hg), without altering diastolic RCA-PP. SAB + MCT rats had improved RV function vs MCT rats, evident from their significantly increased cardiac output (CO), RV free wall (RVFW) thickening, tricuspid annular plane systolic excursion (TAPSE) and RV-PA coupling indices. RV-PA coupling indices and CO correlated directly with systolic RCA-PP. RV perfusion was increased in SAB + MCT vs MCT rats and correlated well with CO; whereas microvascular rarefaction was unaltered. SAB + MCT rats had less RVH and fibrosis and lower PA pressures vs MCT rats. SAB + MCT rats had significantly lower RV pyruvate kinase muscle isoform 2/1 ratios than MCT rats, consistent with restoration of oxidative metabolism. A SAB-induced increase in systolic RCA-PP improves RV perfusion and function in MCT rats. Maintaining systolic RCA perfusion can preserve RV function in PAH.
Identifiants
pubmed: 32339403
doi: 10.1111/apha.13483
pmc: PMC7363583
mid: NIHMS1599099
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13483Subventions
Organisme : NHLBI NIH HHS
ID : RC1 HL099462
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL071115
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL113003
Pays : United States
Informations de copyright
© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
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