Circulation, Vol 79, 920-928, Copyright © 1989 by American Heart Association
IK Jang, HK Gold, AA Ziskind, JT Fallon, RE Holt, RC Leinbach, JW May and D Collen
Acute myocardial infarction is triggered by coronary artery occlusion that
may be recanalized by thrombolytic therapy with a success rate of up to 75%
only. The resistance of coronary artery occlusion to thrombolysis may
either be due to obstruction of the lumen by a nonthrombotic mechanism or
by intrinsic resistance of thrombus to dissolution. Coronary arterial
thrombi are composed of platelet-rich and erythrocyte-rich material in
variable proportions. To evaluate the relative sensitivity of these
thrombus components to thrombolysis, we have used two femoral arterial
thrombosis models in the rabbit, consisting of erythrocyte-rich clot
produced by injecting whole blood and thrombin in an isolated segment and
of platelet-rich thrombus spontaneously formed on an everted (inside out)
femoral arterial segment. Intravenous infusion of recombinant tissue-type
plasminogen activator (rt-PA) at a rate of 30 micrograms/kg/min
consistently reperfused arteries occluded with erythrocyte-rich clot (six
of six animals compared with zero of six placebo-treated animals, p =
0.002), whereas infusion of 30 or 100 micrograms/kg/min was significantly
less efficient for reperfusion of everted segments occluded with platelet-
rich material (only four of 12 animals, p = 0.01). Intra-arterial infusion
proximal to the occlusion, at a rate of 20 micrograms/kg/min reperfused six
of seven rabbits with erythrocyte-rich clots but only one of seven rabbits
with occluded everted segments (p = 0.03). A dose of 100 micrograms/kg/min
was necessary to reperfuse platelet-rich occlusions in five of six
rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. A possible explanation for resistance to coronary thrombolysis
Cardiac Unit, Massachusetts General Hospital, Boston 02114.
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