Conjunctive effects of the 5HT(2) receptor antagonist, sarpogrelate, on thrombolysis with modified tissue plasminogen activator in different laser-induced thrombosis models.
The effect of the serotonin (5HT(2)) receptor antagonist, sarpogrelate, was compared with that of the selective thrombin inhibitor, argatroban, in modified tissue plasminogen activator (mt-PA)-induced thrombolysis using two laser-induced thrombosis models reflecting different levels of vascular endothelial cell damage. Bolus intravenous infusions of mt-PA (0.1, 0.2, 0.4 mg/kg) induced thrombolysis in a dose-dependent manner. Sarpogrelate (4.7 mg/kg b.i. + 1.0 mg/kg/h i.v.) given together with mt-PA (0.2 mg/kg b.i.) optimally enhanced thrombolysis (p < 0.05) in a helium-neon laser-induced model where endothelial damage was minimal but not in an argon laser model where desquamation of endothelial cells was recognized. In contrast, argatroban (0.5 mg/kg b.i. + 0.1 mg/kg/h i.v.) given with mt-PA (0.2 mg/kg b.i.) significantly enhanced thrombolysis in both laser models. The findings indicate that the effectiveness of sarpogrelate in thrombolytic therapy might depend on the extent of vascular damage.
Yamashita
T
T
Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan. tsutomu@nutr.kobegakuin.ac.jp
Kitamori
K
K
Hashimoto
M
M
Watanabe
S
S
Giddings
J C
JC
Yamamoto
J
J
D000818:Animals; D001128:Argon; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology / Q000528:radiation effects; D006371:Helium; D007834:Lasers / Q000009:adverse effects; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D013386:Succinates / Q000008:administration & dosage / Q000494:pharmacology*; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects
D010975:Platelet Aggregation Inhibitors; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D006371:Helium; D001128:Argon; D010959:Tissue Plasminogen Activator