Simple canine model of arterial thrombosis with endothelial injury suitable for investigation of thrombolytic agents.
Three separate studies were done to evaluate a new canine model of arterial thrombosis with endothelial injury. Endothelial injury was produced by exposing the luminal surface of a 2-cm segment of femoral artery to 100 degrees C saline for 5 min. There was no disruption of proximal or distal blood flow with this model, and thrombolysis was continuously monitored by measuring 125I-labelled fibrin gamma emissions from the thrombus. Study No. 1 showed that complete endothelial denudation was achieved with this model. Study No. 2 demonstrated 1) adherence of the experimentally induced thrombus to subendothelial connective tissue, and 2) endogenous thrombolysis of approximately 9% during the initial 2 h after thrombus formation. Study No. 3 tested the usefulness of the model for evaluating the thrombolytic efficacy of urokinase. Urokinase (30,000 U/Kg, bolus IV injection) caused 38 +/- 5.4% thrombolysis within 90 min of drug administration versus 5.9 +/- 2.4% for a saline-treated control group. We conclude that this model provides a technically simple and reproducible method for the laboratory investigation of thrombosis and thrombolysis in arteries with endothelial injury.
Badylak
S F
SF
Hillenbrand Biomedical Engineering Center, Purdue University, W. Lafayette, IN 47907.
Poehlman
E
E
Williams
C
C
Klabunde
R E
RE
Turek
J
J
Schoenlein
W
W
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000648:ultrastructure; D004195:Disease Models, Animal; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D007457:Iodine Radioisotopes; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D013927:Thrombosis / Q000188:drug therapy*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D005343:Fibrinolytic Agents; D007457:Iodine Radioisotopes; D014568:Urokinase-Type Plasminogen Activator