Effect of thromboxane antagonism on recanalization during streptokinase-induced thrombolysis in anesthetized monkeys.
The effect of a selective thromboxane A2 (TxA2) receptor antagonist, SQ 30,741, on streptokinase-induced thrombolysis was examined in pentobarbital-anesthetized cynomolgus monkeys. The intimal surface of a stenosed carotid artery was stimulated with 100 microA anodal current to produce an occlusive thrombus. After 45 min of zero blood flow, a 1-h intraarterial (i.a.) infusion of streptokinase (680 U/min) was injected proximal to the thrombus. Five minutes before streptokinase (SK) intravenous (i.v.) infusions of heparin (200 U/kg + 120 U/h) and either SQ 30,741 (2 mg/kg + 2 mg/kg/min, n = 8) or vehicle (1 ml/h saline, n = 7) were started and maintained for 3 h. In four monkeys not given streptokinase or heparin, no recanalization was detected and occlusive thrombi were observed after 3 h. All animals receiving streptokinase were recanalized. SQ 30,741 had no effect on return of flow during streptokinase infusion, but increased average reflows during the second (60%, p less than 0.05) and third hours (159%, p less than 0.01). Average blood flows were decreased from the second to third hours with vehicle (p less than 0.001) and remained stable with SQ 30,741. Thromboxane antagonism also increased minimal blood flows during the third hour (438%, p less than 0.01) and decreased the total time reoccluded by 73% (p less than 0.05). However, SQ 30,741 had no effect on the time to recanalization, the maximum reflow, and both number of animals reoccluded and average number of reocclusions. Fibrinogen levels were equivalently diminished (8%, p less than 0.05), and platelet counts were unaffected in both treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Schumacher
W A
WA
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
Heran
C L
CL
D000818:Animals; D002340:Carotid Artery Diseases / Q000503:physiopathology; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D013300:Streptokinase / Q000494:pharmacology*; D013927:Thrombosis / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology
C054215:SQ 30741; D013928:Thromboxane A2; D013300:Streptokinase