The
Parkes Weber syndrome is a congenital
vascular malformation, characterized by
varicose veins, arterio-venous
fistulas and overgrown limbs. No broadly accepted animal model of
Parkes Weber syndrome has been described. We created side-to-side arterio-venous
fistula between common femoral vessels with proximal non-absorbable
ligature on common femoral vein limiting the enlargement of the vein diameter in Wistar rats. Contralateral limb was
sham operated. Invasive blood pressure measurements in both iliac and inferior cava veins were performed in rats 30 days after
fistula creation. Tight circumference and femoral bone length were measured. Histopathology and morphology of soleus muscle, extensor digitorum longus muscle, and the common femoral vessel were analyzed. 30 days following arterio-venous
fistula creation, a statistically significant elevation of blood pressure in common iliac vein and limb overgrowth was observed. Limb enlargement was caused by muscle overgrowth,
varicose veins formation and bone elongation. Arterio-venous
fistula with proximal outflow limitation led to significant increase of femoral vein circumference and venous wall thickness. Our study indicates that the described rat model mimics major clinical features characteristic for the human
Parkes Weber syndrome: presence of arterio-venous
fistula, venous
hypertension and dilatation,
varicose veins formation, and the limb
hypertrophy. We reveal that limb overgrowth is caused by bone elongation, muscle
hypertrophy, and venous dilatation. The newly established model will permit detailed studies on the mechanisms underlying the disease and on the efficacy of novel therapeutic strategies for the
Parkes Weber syndrome treatment.