Circulation, Vol 82, 169-177, Copyright © 1990 by American Heart Association
RJ Shebuski, IJ Stabilito, GR Sitko and MH Polokoff
The effect of tissue-type plasminogen activator (t-PA) alone or in
combination with heparin, the Arg-Gly-Asp-containing peptide bitistatin, or
both heparin and bitistatin was evaluated on thrombolysis time and acute
reocclusion in a canine model of coronary thrombosis. Thrombus formation
was elicited by electrolytic injury with a needle electrode to the
endothelial surface of the circumflex coronary artery in the open-chest,
anesthetized dog in the presence of a flow-limiting critical stenosis.
Thirty minutes after spontaneous coronary artery occlusion, t-PA (1 mg/kg
i.v. over 90 minutes) was administered. Group 1 was given t-PA alone;
reperfusion occurred at 78.2 +/- 5.6 minutes with a reperfusion incidence
of 60% (6/10). Group 2 received t-PA plus heparin (100 units/kg plus 50
units/kg/hr); reperfusion occurred at 61.9 +/- 9.1 minutes with a
reperfusion incidence of 90% (9/10). Group 3 received t-PA plus heparin
plus bitistatin (30 micrograms/kg plus 3 micrograms/kg/min); reperfusion
occurred at 47.3 +/- 7.6 minutes (p less than 0.05 versus group 1) with a
reperfusion incidence of 90% (9/10). Group 4 received t-PA plus bitistatin,
and reperfusion occurred at 51.8 +/- 8.5 minutes; however, the reperfusion
incidence was only 60% (6/10). In groups 1, 2, and 4, acute reocclusion
occurred in more than 80% of the reperfused dogs, whereas in group 3
reocclusion occurred in 22% (2/9) of the reperfused dogs (p less than 0.05
versus group 1). The dose of heparin used in this study increased activated
partial thromboplastin times 1.5-2.0- fold over control.(ABSTRACT TRUNCATED
AT 250 WORDS)
ARTICLES
Acceleration of recombinant tissue-type plasminogen activator-induced thrombolysis and prevention of reocclusion by the combination of heparin and the Arg-Gly-Asp-containing peptide bitistatin in a canine model of coronary thrombosis
Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
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