Circulation, Vol 77, 678-684, Copyright © 1988 by American Heart Association
P Golino, JH Ashton, P Glas-Greenwalt, J McNatt, LM Buja and JT Willerson
Human recombinant tissue-type plasminogen activator (rt-PA) has been shown
to be an effective and safe agent for coronary thrombolysis in patients
with acute myocardial infarction. However, thrombolysis is associated with
a high rate of acute reocclusion after discontinuation of rt-PA. The goals
of the present study were to assess whether reocclusion after thrombolysis
is caused by intracoronary platelet aggregation and to determine the role
of thromboxane A2 (TxA2) and serotonin (5HT) in mediating this phenomenon.
Accordingly, coronary thrombosis was induced in anesthetized, open-chest
dogs by insertion of a copper coil into the left anterior descending
coronary artery (LAD). LAD blood flow was monitored throughout the
experiment by means of a Doppler flow probe placed proximally to the coil.
Thrombolysis was achieved with rt-PA (0.05 mg/kg bolus + micrograms/kg/min
infusion) in 23 +/- 3 min. rt-PA was then discontinued and each animal
received a bolus of heparin (150 U/kg) every hour. Reperfusion was followed
by repeated cycles of gradual occlusions followed by spontaneous
restorations of blood flow (cyclic flow variations, CFVs) before a
persistent occlusion recurred. In control dogs (n = 6), heparin alone did
not prevent CFVs and reocclusion time was 25 +/- 4 min. Administration of
an intravenous bolus of 0.2 +/- 0.06 mg/kg SQ29548, a TxA2/prostaglandin
H2-receptor antagonist, and an intravenous bolus of 0.2 +/- 0.04 mg/kg
ketanserin, a 5HT2-receptor antagonist, completely abolished CFVs in six of
six dogs and reocclusion time was greater than 158 +/- 14 min (p less than
.01).(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Mediation of reocclusion by thromboxane A2 and serotonin after thrombolysis with tissue-type plasminogen activator in a canine preparation of coronary thrombosis
Department of Internal Medicine (Cardiology Division), University of Texas Health Science Center, Dallas 75235-9047.
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