Direct tissue plasminogen activator administration through a microinjection device in a pig model of retinal vein thrombosis.
OBJECTIVE
This study sought to analyze the changes to clots and retinal tissue following direct infusion of tissue plasminogen activator (tPA) at different rates to the obstructed area of the retinal vein in an experimental animal model of retinal vein occlusion.


METHODS
The miniature pigs, which underwent unilateral retinal vein thrombosis generated by a combination of light illumination of the retinal vein and I.V. administration of rose Bengal, were randomly divided into two groups. In the experimental group (n = 45), balanced salt solutions + tPA were infused into the obstructed retinal vein at different rates (30,60, and 80 ml/h) for 20 minutes (15 pigs in each subgroups). In the control group (n = 5), balanced salt solutions without tPA were infused. Retinal tissue and clots were evaluated by fundus photographic and histopathologic analysis.


RESULTS
Clot lysis occurred in 2/15, 9/15, and 10/15 pigs respectively following the 30, 60, and 80 ml/h tPA infusion. Exudative retinal detachment appeared in 12/15 pigs after infusion of tPa at a rate of 80 ml/h. Retinal histopathology and transmission electron microscopy showed that endothelial cell tight junctions of retinal vein and capillaries were injured in pigs receiving the 80 ml/h tPA infusion.


CONCLUSIONS
Experiments with our pig model suggests that the optimal infusion rate for the treatment of retinal vein thrombosis by direct tPA infusion is 60 ml/h for 20 minutes.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008845:Microinjections; D012160:Retina / Q000187:drug effects / Q000473:pathology; D012169:Retinal Vein; D012171:Retinal Vessels / Q000187:drug effects*; D013552:Swine; D013556:Swine, Miniature; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator