Abstract
A new model suitable for the quantitation of Li vivo thrombolytic efficacy was developed which has significant advantages over currently available models. This model allows animals to be used repeatedly and produces data that are less variable.This is a species-independent model utilizing an arterio-venous shunt (AVS). This model was used in rabbits (3 kg) and beagle dogs (13 kg). Each animal was used repeatedly during a 7 day experimental period without evidence of antibody formation. Clot lysis data are less variable than the rabbit jugular vein clot lysis model (RJV). The average coefficient of variation at all doses ([SD/Mean]×l00) with the AVS model was 13±9 and 21±6 for dogs and rabbits, respectively, compared to 25±11 for the RJV model. The rate of data accunulation with the AVS is 3-fold greater than the RJV.In the dog, catheters (25 cm long, 1.6 mm ID) were placed in the jugular vein and the carotid artery, tunneled under the skin to the back of the neck, exteriorized and plugged with a heparin lock. Thrombi were made from a donor dog by placing 0.7 ml of whole blood in a 1 cc plastic syringe barrel containing a cotton thread. The blood was clotted for 2 hr at 37.5 deg C, in vitro. The thrombus was rinsed and the syringe barrel was connected into the circulation by silicone tubing for a 90 min test period. Clot lysis was determined by weight. The flow rate across the thrombus was regulated to 60 ml/min by placing a teflon capillary tube (30 cm, o.7 mm OD) on the venous side. The procedure for the rabbit study differed as follows: Rabbit blood made larger clots therefore the blood was diluted with saline (4 to 1). Clots were incubated 90 min in vitro. The flow rate was 40 ml/min. Clot lysis was measured by the loss of 125-1 fibrinogen.The dose of reccminant t-PA (ActivaseR, Actilyse™) that achieved 40% lysis (ED40) was determined to be 180 ugAg in the dog and 660 ugAg in the rabbit AVS model. Using the RJV model the ED40 was 340 ug/kg.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
