Patent foramen ovale: standards for a preclinical model of prevalence, structure, and histopathologic comparability to human hearts.
BACKGROUND
This study evaluated and standardized a Patent Foramen Ovale (PFO) preclinical model in gross anatomic and histopathologic features.


METHODS
We examined 150 necropsy-derived domestic porcine hearts, age 4-6 months for PFO prevalence, appearance, and size. Histopathologic preparations were standardized and processed identically to 24 post-mortem human hearts aged 16-62 years. A measurement scheme was developed for PFO atrial openings, tunnel length, and histopathologic features to compare porcine and patient hearts.


RESULTS
PFO was found in 32 of the 150 porcine hearts (prevalence 21.3%). Twenty-five porcine PFO underwent standard characterization by tunnel length, and right, and left atrial orifice diameters. Logarithmic regression analysis between porcine PFO tunnel length and left atrial orifice area demonstrated a significant positive relationship (P = 0.0162, R(2) = 0.227). The porcine PFO tunnel length was significantly longer than in humans (12.0 +/- 4.0 mm vs. 7.1 +/- 3.1 mm respectively, P < 0.0001). Histopathologic comparison was made using serial sections perpendicular to the atrial septum and the tunnel long axis. Human and porcine PFO lesions demonstrated strong similarities in tissue cells, connective tissue, and matrix composition.


CONCLUSIONS
PFO assessment was standardized in both macroscopically and histopathologically, with quantitative and qualitative comparisons feasible using a porcine preclinical model. PFO prevalence in domestic swine is identical to humans, and microscopic structures very similar to humans. The domestic swine PFO model appears useful to evaluate new interventional closure technologies due to comparability in microscopic features. Tunnel length should be carefully evaluated due to differences across pigs and patients.
Hara
Hidehiko
H
Minneapolis Heart Institute and Foundation, Minneapolis, Minnesota 55407, USA.
Virmani
Renu
R
Ladich
Elena
E
Mackey-Bojack
Shannon
S
Titus
Jack L
JL
Karnicki
Krzysztov
K
Stewart
MaryLou
M
Pelzel
Jamie M
JM
Schwartz
Robert S
RS
D000293:Adolescent; D000328:Adult; D000818:Animals; D002102:Cadaver; D006344:Heart Septal Defects, Atrial / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D015995:Prevalence; D012016:Reference Values; D012189:Retrospective Studies; D013552:Swine