A new rat model of arterial thrombosis with a platelet-rich head and an erythrocyte-rich tail: thrombolysis experiments with specific thrombin inhibition.
A model for thrombolysis in rats was developed. Repeated, focal external heating was applied to the carotid artery which leads to the development of a cyclic blood flow with slow, steady decreases followed by abrupt increases. When this cyclic blood flow stops spontaneously, the entire arterial segment (approximately 10 mm) can be demarcated with snares to create an arterial thrombus of fixed size, with a platelet-rich head and an erythrocyte-rich tail. The usefulness of the model was tested by evaluating the thrombolysis induced by a low dose of recombinant tissue-type plasminogen activator (rt-PA) alone and rt-PA in combination with standard heparin and recombinant hirudin. Re-canalization of the artery was measured as blood flow and as the residual 125I-radioactivity in the artery at the end of the experiment, resulting from 125I-fibrinogen incorporated during the formation of the thrombus. Both blood flow and 125I-activity measurements show that hirudin, but not heparin in combination with rt-PA, significantly improves thrombolysis, which is in accordance with previous experimental findings. It is concluded that the model, with a thrombus resembling the thrombus found in man after coronary occlusion, enables complicated experiments with thrombolysis frequently performed only in large animals to be performed in rats.
Astra Hässle AB, Preclinical R & D, Mölndal, Sweden.
S
S
Lenfors
L
L
Marberg
S
S
Wikström
U
U
Jonsson
A W
AW
Eriksson
D
D
Gustafsson
D000818:Animals; D001792:Blood Platelets; D002339:Carotid Arteries; D004195:Disease Models, Animal; D004338:Drug Combinations; D004912:Erythrocytes; D006629:Hirudins / Q000494:pharmacology*; D006358:Hot Temperature; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013927:Thrombosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D004338:Drug Combinations; D006629:Hirudins; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator