A Novel Model of Spontaneous Arteriovenous Fistula Formation

Aims: Most In vivo angiogenesis studies have been performed by setting an ischemic condition, or by administrating angiogenic factors such as vascular endothelial growth factor. Unexpectedly, we discovered to spontaneously create new blood vessels by just suturing an arterial graft patch in the jugular vein, using a rabbit model. In general, arteriovenous malformations consist of tangles of arteries and veins that are often connected by a fistula. However, the causes and mechanisms of these clinical entities are not fully understood. The purpose of this study is to show the methods used to produce the model, and then to report the chronological processes involved in the development of this neovasculature and the change of endogenous angiogenic factors. Methods and Results: We performed to suture an arterial graft patch into the rabbit vein. Within a month after the surgery, dense (nidus-like) neovasculature was formed around the patch. Angiography and pulse-oximeter analyses demonstrated that the blood, which flew into the new vessels, was arterial blood. It means that arteriovenous shunt has been formed.. Pathological evaluation revealed multiple branching vessels sprouting out from the patch suture site, and numerous dilated vessels devoid of sphincter muscle in the surrounding connective tissue. We determined, by FISH analysis, that these branches had originated from the graft itself. The endogenous angiogenic factors, such as VEGF, have soared immediately after the surgery. Conclusion: This is the first in vivo model of spontaneous arteriovenous fistula formation via the creation of neovasculature. These findings exemplify the difference between the arterial and venous intima, and we believe that this difference could be key to understanding human vascular anomaly diseases and the basic principles of vascular network formation, angiogenesis and/or vasculogenesis.