Administration of SQ29548 and ketanserin completely abolished cyclic flow variations and prolonged reocclusion time (>158 vs 25 min, p<0.01) compared to heparin alone in a canine thrombosis model.
Does combined TxA2 and 5HT2 receptor antagonism prevent reocclusion and cyclic flow variations after rt-PA thrombolysis in a canine model of coronary thrombosis?
Combined antagonism of thromboxane A2 and serotonin receptors prevents acute reocclusion and cyclic flow variations after rt-PA thrombolysis in a canine model of coronary thrombosis.
Absolute Event Rate: 158% vs 25%
p-value: p=<0.01
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)
Golino et al. (1988) studied Coronary thrombosis (n=12). SQ29548 and ketanserin vs. Heparin alone was evaluated on Reocclusion time (p=<0.01). Administration of SQ29548 and ketanserin completely abolished cyclic flow variations and prolonged reocclusion time (>158 vs 25 min, p<0.01) compared to heparin alone in a canine thrombosis model.