An ovine model of pulmonary insufficiency and right ventricular outflow tract dilatation.
OBJECTIVE
The treatment of pulmonary insufficiency (PI) following reconstructive surgery of the right ventricular outflow tract (RVOT) in repair of the tetralogy of Fallot remains a significant challenge. The study aim was to establish an ovine model of dilated RVOT and PI, and to quantify the degree of PI and right ventricular remodeling over an eight-week period, using magnetic resonance imaging (MRI).


METHODS
Five sheep underwent baseline MRI scanning and catheterization. The weight-indexed right and left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and pulmonary regurgitant fraction (RF) were measured at baseline. The animals then underwent pulmonary valvectomy and transannular patch repair of the RVOT. Repeat MRI and hemodynamic measurements were obtained after an eight-week period.


RESULTS
The indexed RVEDV increased from 49 +/- 4.0 ml/m2 at baseline to 80 +/- 10.3 ml/m2 at eight weeks after valvectomy (p = 0.01), while the indexed RVESV increased from 13 +/- 3.4 ml/m2 to 33 +/- 8.8 ml/m2 (p = 0.01). The indexed RVSV increased from 36 +/- 3.7 ml/m2 to 47 +/- 1.7 ml/m2 (p = 0.01). The RVEF at baseline was 74 +/- 6%, and this decreased to 59 +/- 5% at follow up (p = 0.02). The RF at baseline was 0 +/- 0% and was increased to 37 +/- 3% at eight weeks after valvectomy (p < 0.001). The left ventricular (LV) function was also diminished: LVEF at baseline was 67 +/- 2%, versus 49 +/- 10% at follow up (p = 0.01). Both, the RV and LV end-diastolic pressures were significantly elevated at follow up.


CONCLUSIONS
All five animals developed pulmonary regurgitation sufficient to cause significant RV dilatation and diminished RV and LV functions. This model may be used to investigate novel therapeutic approaches in the treatment of this difficult clinical problem.
Department of Pediatric Cardiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
J Daniel
JD
Robb
Matthew A
MA
Harris
Masahito
M
Minakawa
Evelio
E
Rodriguez
Kevin J
KJ
Koomalsingh
Takashi
T
Shuto
Yoav
Y
Dori
Robert C
RC
Gorman
Joseph H
JH
Gorman
Matthew J
MJ
Gillespie
D000818:Animals; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D011651:Pulmonary Artery / Q000473:pathology*; D011665:Pulmonary Valve Insufficiency / Q000209:etiology / Q000473:pathology*; D012756:Sheep