Supra-coronary aortic banding improves right ventricular function in experimental pulmonary arterial hypertension in rats by increasing systolic right coronary artery perfusion

Lian Tian, Ping Yu Xiong, Elahe Alizadeh, Patricia D. A. Lima, François Potus, Jeffrey Mewburn, Ashley Martin, Kuang-Hueih Chen, Stephen L. Archer

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Aim -- 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. Methods -- 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, 99mTc-sestamibi single-photon emission computed tomography (SPECT) and microsphere infusion studies were performed. The RV was harvested for measurement of hypertrophy (RVH), fibrosis and immunoblotting, and the lung was harvested for pulmonary artery (PA) histology. Results -- 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. Conclusion -- 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.
Original languageEnglish
Article numbere13483
JournalActa Physiologica
Volume229
Issue number4
Early online date17 May 2020
DOIs
Publication statusPublished - 31 Aug 2020

Keywords

  • coronary artery
  • microvascular rarefaction
  • mitochondrial metabolism
  • monocrotaline
  • pyruvate dehydrogenase kinase
  • single-photon emission computed tomography (SPECT)

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