title: Right ventricular remodeling in restrictive ventricular septal defect.
abstract: Restrictive ventricular septal defect (rVSD) presents with little/no hemodynamic aberrations despite a patent septal defect. Clinically, these patients are observed with the hope that the defect will functionally close over time without the need for surgical repair and development of heart failure. Without evidence supporting a definitive therapeutic strategy, rVSD patients may have increased risk of a poor outcome. We tested the hypothesis that rVSD results in subclinical RV diastolic dysfunction and molecular remodeling. Five pigs underwent surgical rVSD creation. Echocardiography, hemodynamics, myocyte contractility experiments, and proteomics/Western blot were performed 6-weeks post-rVSD and in controls. *p<0.05. LV and RV hemodynamics in rVSD were comparable to controls. The tricuspid valve early/late diastolic inflow velocity ratio (TV E/A ratio) decreased from 1.6+/-0.05 in controls to 1.0+/-0.08* in rVSD, indicating RV diastolic dysfunction. rVSD RV myocytes showed abnormalities in contraction (departure velocity (Vd) -51%*, Vd time +55%*) and relaxation (return velocity (Vr) -50%*, Vr time +62%*). Mitochondrial proteins (fatty acid, TCA cycle) increased 2-fold*, indicating heightened RV work. Desmin protein upregulated 285%* in rVSD RV myocardium, suggesting cytoskeletal remodeling. rVSD causes RV diastolic dysfunction, myocyte functional impairment, and mitochondrial/cytoskeletal protein upregulation in our model. Desmin upregulation may hinder sarcomeric organization/relaxation, representing a key subclinical early marker for future RV dysfunction. TV E/A measurements are a non-invasive modality to assess rVSD patients for diastolic dysfunction. Translational research applications may lead to fundamental changes in the clinical management of rVSD by providing evidence for early repair of the defect.
authors.affiliation: Department of Anesthesiology, The Ohio State University, Columbus, OH, USA.
authors.forename: Gretel
authors.initials: G
authors.lastname: Monreal
authors.forename: Dane J
authors.initials: DJ
authors.lastname: Youtz
authors.forename: Alistair B
authors.initials: AB
authors.lastname: Phillips
authors.forename: Mahala E
authors.initials: ME
authors.lastname: Eyman
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Gorr
authors.forename: Christina
authors.initials: C
authors.lastname: Velten
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Lucchesi
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gerhardt
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004452:Echocardiography; D004591:Electrophoresis, Polyacrylamide Gel; D006345:Heart Septal Defects, Ventricular / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D013552:Swine; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology*; D020257:Ventricular Remodeling / Q000502:physiology*