The protective effect of heparin in a dog model of rethrombosis following pharmacologic thrombolysis.
Rethrombosis is an important clinical problem for patients who have benefitted from pharmacologic thrombolysis. The present study describes a dog model of arterial thrombosis, which includes endothelial denudation, intimal damage, and stenosis, and is suitable for studying the phenomena of both thrombolysis and subsequent rethrombosis. The model was used to determine the effect of tissue-type plasminogen activator (t-PA), high and low dose heparin, and saline upon the incidence of rethrombosis after t-PA-induced thrombolysis. Initial thrombolysis with reflow was achieved with 0.4 mg/kg t-PA, intravenous bolus injection, followed immediately by 0.4 mg/kg t-PA, 30 min infusion, in 40 of 42 dogs (95%) that had an occlusive, 125I-labelled thrombus created in a segment of femoral artery. The 40 dogs in which reperfusion was achieved were randomly sorted into 4 groups of 10 each which then received either saline, t-PA (0.4 mg kg-1 infused over 1 h), low dose heparin (500 U bolus injection then 250 U h-1 for 24 h), or high dose heparin (1,500 U bolus injection then 500 U h-1 for 24 h). Sixty percent (6/10) of the saline treated dogs showed occlusive rethrombosis at 24 h. The incidence of occlusive rethrombosis was 9/10 in the t-PA treated group (p = NS), 3/10 in the low dose heparin treated group (p = NS), and 0/10 in the high dose heparin treated group (p less than 0.01). Two smaller groups consisting of 5 dogs each were treated with either saline or high dose heparin alone (no t-PA). None of the dogs in either group showed thrombolysis with reflow.(ABSTRACT TRUNCATED AT 250 WORDS)
Voytik
S
S
Hillenbrand Biomedical Engineering Center, Purdue University, W. Lafayette, IN 47907.
Badylak
S F
SF
Burke
S
S
Klabunde
R E
RE
Henkin
J
J
Simmons
A
A
D000818:Animals; D001780:Blood Coagulation Tests; D004195:Disease Models, Animal; D004285:Dogs; D006493:Heparin / Q000627:therapeutic use*; D012008:Recurrence; D013927:Thrombosis / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014654:Vascular Patency / Q000187:drug effects
D006493:Heparin; D010959:Tissue Plasminogen Activator