Chronic Cerebral Arteriovenous Malformation Model In Swine: Heomdynamics And Vascular Remodeling

Background and Objectives: Cerebral Arteriovenous malformation (AVM) is the most common cerebrovascular malformation. The clinical manifestations contain hemorrhage, refractory headache, and epilepsy etc. Part of the patients show progressive hemiparalysis due to long-term intracephalic blood steal. It severely threatens the quality and safety of life. Although AVM has complicated clinical manifestations and is hard to deal with, little of its chronic change of hemodynamics and vascular remodeling is reported in prior study.In order to conduct an intensive study of cerebral arteriovenous malformation,a variety of AVM models had been established, whether in vitro models or in vivo arteriovenous fistula models, all of which have different drawbacks. Scholars had already used pig skull base RM as a vascular malformation company to establish AVM animal models, among which the Massoud model is the most famous, but currently the model is only used for the short-term research due to rapid spontaneous thrombosis. For the same reason other models on account of Massoud model could not be used as stable animal models, and because of limited numbers and no comparison, recent related research did not obtain dependable conclusions. Up to the present,there is not a stable AVM model which could be used for the systematic study of the characteristics of hemodynamics and vascular remodeling of chronic AVMs.The purpose of our research is to improve the method of establishment on the basis of previous experience, and to compare the different anastomosis styles, afer a long-term follow-up, in order to establish a simple, economical, stable brain AVM model more similar to human AVMs. Then the systematic study of the chronic changes of hemodynamics and vascular remodeling is carried out on the basis of a successful model.Methods: Using Chinese experimental mini-pig (CEMP)'s rete mirabile (RM) as the AVM nidus, we created the brain AVM model in 13 swines.Two possible types of surgical anastomoses between left common carotid artery (CCA) and left external jugular vein (EJV) were deliberately created, including end-to-end in 7 cases and side-to-side in 6 cases. Occlusion of the external carotid artery (ECA) was achieved by direct surgical ligation, and the ipsilateral muscular branch of ascending pharyngeal artery (APA) and occipital artery (OA) were kept open. A long time follow-up as long as 11-18 months (mean 464.7days) was taken, to compare the difference betweem two groups in the difficulty of model establishment,success rate , occlusion rate of anastomotic fistula, the stability, and the similarity to the human cerebral AVM in vascular structure and angiographic imaging. Meanwhile the measurement of the pressure and diameters of the main vessels, RM-volume and the shunting time was also carried out and followed up.Results: Successful brain AVM model was achieved in 12 out of 13 animals. The angiography showed that the right ECA also fed the RM by RA and AA. The results showed end-to-end anastomosis was easier. Angiography showed that end-to-end anastomosis led to a faster shunting than the side-to-side anastomosis, and the end-to-end anastomosis models had a higher success rate and a lower occlusion rate than the side-to-side anastomosis. After the models were established successfully, between the left VA and left APA (by left APA descending branch) and left CCA (by left OA descending branch) immediately formed the arterio-arterial anastomoses spontaneously, i.e., pseudo-arteriovenous fistula (pAVF). So the successful models contained not only more than one arteries, but also both plexiform AVM and arteriovenous fistula, i.e., a two-in-one model. Direct surgical ligation of the ECA was simple, economical,and dependable. In all the models, the diameter of descending branchs of R-APA, APA and the volume of RM increased markedly with the time (P<0.05), the diameter of L-APA had a tendency to increase (P=0.065); the pressure of R-APA and the pressure gradient through the retia increased markedly with time ( P<0.05). The change is more remakable in the end-to-end anastomosis models than in the side-to-side anastomosis ones. Meanwhile vascular dilation and tortuosity of the feeding arteries of the pAVF were also becoming more and more evident angiographically.Conclusions: After comparision we found a better method to establish a chronic AVM animal model in swine closer to human AVMs,i.e.,by CCA-EJV end-to-end anastomosis and direct surgical ligation of the ipsilateral ECA. The hemodynamic changes led to the changes of vascular remodeling such as dilation and tortuosity of the main feeding arteries and draning veins, and also the increase of the RM-volume.The pressure gradient through the retia increased significantly and the dominant factor associated with rhe reduced resistance to flow in the chronic animals was the increased luminal diameter of the rete vessels.