Jiaquan Zhu, HarukiIde, Yaqin Yana Fu, Anouk-Martine Teichert, Hideyuki Kato, Richard D. Weisel, Jason T. Maynes, John G. Coles, Christopher A. Caldarone
The Hospital for Sick Children and University of Toronto. Toronto General Hospital.
Canada
Journal of Thoracic and Cardiovascular Surgery
J Thorac Cardiovasc Surg 2014; 148: 2550-2557
DOI: 10.1016/j.jtcvs.2014.07.050
Abstract
Objectives: Pulmonary vein stenosis (PVS) is a relentless disease with a poor prognosis. Although surgical repair can effectively treat “downstream” (near left atrial junction) PVS, residual “upstream” (deep in lung parenchyma) PVS commonly dictates long-term survival. Our initial studies revealed an association between PVS and transforming growth factor-β signaling, which led us to investigate the effect of losartan on upstream pulmonary vein vasculopathy in a piglet model of PVS.
Methods: Neonatal Yorkshire piglets underwent sham surgical banding (sham, n = 6), staged bilateral pulmonary vein banding of all pulmonary veins except the right middle pulmonary vein (banded, n = 6), and staged pulmonary vein banding with losartan treatment (losartan, 1 mg/kg/d, n = 7). After 7 weeks, the hemodynamic data were obtained and the piglets killed.
Results: Pulmonary vein banding (compared with sham) was associated with continuous turbulent flow in banded pulmonary veins, pulmonary hypertension (pulmonary artery/systemic blood pressure ratio 0.51 ± 0.06 vs 0.23 ± 0.02, P < .001), and diffuse pulmonary vein intimal hyperplasia in the upstream pulmonary veins (P < .001). Losartan administration decreased the pulmonary artery/systemic blood pressure ratios compared with those in the banded piglets (0.36 ± 0.08 vs 0.51 ± 0.06, P = .007) but it remained greater than those in the sham group (P = .001). Losartan was also associated with diminished pulmonary vein intimal hyperplasia compared with that in the banded piglets (P < .001) but still remained more than that in the sham group (P = .035). Pulmonary vein banding reduced vascular endothelial-cadherin expression, indicative of diminished endothelial integrity, which was restored with losartan.
Conclusions: Losartan treatment improved PVS-associated pulmonary hypertension and intimal hyperplasia and might be a beneficial prophylactic therapy for patients at high risk of developing PVS after pulmonary vein surgery.
Category
Stenosis or Obstruction of Normal Pulmonary Venous Connections
Pulmonary Venous Pathology
Medical Therapy to Prevent Progression of Disease. Efficacy or Lack of Efficacy
Year of Publication: 2014
Age Focus: Pediatric
Article Type: Animal Models of Disease and Therapy. Studies of Vascular Biology and Mechanism of Disease.
Article Access: Free PDF File or Full Text Article Available Through PubMed or DOI: Yes