The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
Toshihiko Uematsu - One of the best experts on this subject based on the ideXlab platform.
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Plasmin generation plays different roles in the formation and removal of arterial and venous thrombus in mice.
Thrombosis and Haemostasis, 2017Co-Authors: Hiroyuki Matsuno, Osamu Kozawa, Kiyotaka Okada, Shigeru Ueshima, Osamu Matsuo, Toshihiko UematsuAbstract:The role of plasminogen (Plg) and α2-antiplasmin (α2-AP) in Vascular thrombolysis in vivo was investigated in mice deficient in plasminogen (Plg -/-) or α2-AP (α2-AP -/-) or their wild type (PAI-1 +/+, α2- AP +/+). A thrombus was induced in the murine carotid artery or the internal jugular vein by endothelial injury. Blood flow was continuously monitored for 90 min and for 6 h 30 min after the initiation of endothelial injury. The times to occlusion by the developing thrombus in the carotid artery and the jugular vein of wild type mice were 12 ± 1.8 and 7.2 ± 1.9 min, respectively. The arterial thrombus formation in α2- AP -/- mice was indistinguishable from the one in wild type mice, whereas the time to occlusion in Plg -/- was significantly shortened to 5.9 ± 1.7 min. Vascular Patency after spontaneous reperfusion was markedly improved in α2-AP -/- mice. On the contrary, arterial Patency in Plg -/- mice was aggravated. In venous thrombus formation, the time to occlusion in α2-AP -/- mice was significantly prolonged (27.1 ± 5.2 min), whereas in Plg -/- it was slightly shortened to 6.5 ± 2.5 min. Vascular Patency after spontaneous reperfusion was also improved in α2-AP -/- mice, but not in Plg -/- mice. Histological observations using SEM indicated that fibrin nets were firmly fixed on the injured area in Plg -/- mice, but not in α2-AP -/- mice. The tail bleeding time was not different in any type of mice. However, re-bleeding time using a template bleeding device was significantly prolonged in α2-AP -/- as compared with that of wild type mice. In conclusion, lack of plasminogen markedly reduces the antithrombotic activities in vivo, whereas α2-AP plays a more important role in the formation and removal of venous thrombus in mice. Consequently, the inhibition of α2-AP could be a useful tool for the therapy of venous thrombosis and the prevention of re-thrombus formation.
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Effect of GR144053, a fibrinogen-receptor antagonist, on thrombus formation and Vascular Patency after thrombolysis by tPA in the injured carotid artery of the hamster.
Journal of Cardiovascular Pharmacology, 1998Co-Authors: Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Kumiko Tanabe, Motoi Nishida, Hidehiko Hayashi, Toshihiko UematsuAbstract:: The antithrombotic effect of GR144053, which inhibits platelet aggregation by binding to the fibrinogen receptor (glycoprotein IIb/IIIa), was investigated in vitro and in vivo by using hamsters. This compound inhibited the platelet aggregation induced by adenosine diphosphate (ADP; 2.5 microM) with a mean inhibitory concentration (IC50) value of 2.2 +/- 0.4 x 10(-5) M. Vascular injury was inflicted in one carotid artery by using a modified catheter to produce endothelial denudation. In the control group, arterial blood flow was interrupted 4.4 +/- 2.3 min (n = 12) after the injury. When GR144053 continuously infused intravenously at doses of 0 (saline) 0.1, 0.3, and 1.0 mg/kg/h (n = 8, each), the time that elapsed before the vessel became completely obstructed was prolonged in a dose-dependent manner. In separate experiments, reperfusion could be obtained by continuous infusion of tissue-type plasminogen activator (tPA; 0.52 mg/kg) starting 30 min after the initiation of thrombus formation. When GR144053 (0.3 and 1.0 mg/kg/h) was infused in addition to tPA, the incidence of reperfusion and the later Patency of the reperfused artery were much improved as compared with tPA alone. The bleeding time at the end of tPA infusion was significantly prolonged in the presence of the highest dose of GR144053. Next, neointima formation was evaluated 2 weeks after the Vascular injury. When GR144053 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 14 days, the neointimal area was significantly reduced. In separate hamsters, the proliferating index of smooth muscle cells (SMCs) by using bromodeoxyuridine (BrdU) was investigated, and treatment with both tPA and GR144053 significantly decreased the SMC proliferation index in vivo. However, in the in vitro experiments using a hamster SMC line, GR144053 did not have an inhibitory effect on SMC proliferation. These findings suggest that GR144053 inhibits platelet activation on the injured artery and improves Vascular Patency after thrombolysis with tPA, which furthermore results in suppression of neointima formation.
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antiplatelet effect of fk633 a platelet glycoprotein iib iiia antagonist on thrombus formation and Vascular Patency after thrombolysis in the injured hamster carotid artery
Thrombosis and Haemostasis, 1997Co-Authors: Takehiro Kaida, Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Hideo Miyata, Toshihiko UematsuAbstract:: The antithrombotic and restenosis-preventing effects of FK633, an inhibitor of platelet aggregation via binding to the glycoprotein (GP) IIb/IIIa receptor, were studied, IC50 value of FK633 against platelet aggregation ex vivo induced by 2.5 microM adenosine diphosphate (ADP) was 5.4 x 10(-7) M as determined using hamster platelet rich plasma. The inhibitory effect was also investigated in vivo on thrombus formation at the carotid arterial wall injured by a modified catheter. As a control, the left carotid artery was injured and the time required to develop a thrombotic occlusion (3.9 +/- 1.1 min, mean +/- S.E.M., n = 18) was determined. Then, the right carotid artery of the same animal was injured while a continuous intravenous (i.v.) infusion of FK633 was administered at doses of 0 (saline), 0.1, 0.3 or 1.0 mg/kg/h. The time to occlusion was dose-dependently prolonged. In a separate experiment, 10% of the total tPA dose (0.52 mg/kg) was injected into the injured artery as a bolus and the remaining was infused i.v. at a constant rate for 30 min. When FK633 (0.3 or 1.0 mg/kg/h) was infused together with tPA, late Patency of the reperfused artery was much improved as compared with that of treatment with tPA alone. Bleeding time, measured at the end of the tPA infusion, was markedly prolonged when the higher dose of FK633 (1.0 mg/kg/h) was coadministered, however coadministration of the lower dose of FK633 (0.3 mg/kg/h) was almost without prolongation on the bleeding time, despite a significant effect on the Vascular Patency after thrombolysis. Next, neointima formation was evaluated 2 weeks after the Vascular injury. When FK633 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 3, 7 or 14 days after the Vascular injury, the neointimal area formation was significantly suppressed in the treatment groups for 7 or 14 days. These findings suggest that FK633 inhibits platelet activation in the injured artery and improves Vascular Patency after thrombolysis with tPA with a concomitant suppression of neointima formation.
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Antiplatelet effect of FK633, a platelet glycoprotein IIb/IIIa antagonist, on thrombus formation and Vascular Patency after thrombolysis in the injured hamster carotid artery.
Thrombosis and Haemostasis, 1997Co-Authors: Takehiro Kaida, Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Hideo Miyata, Toshihiko UematsuAbstract:: The antithrombotic and restenosis-preventing effects of FK633, an inhibitor of platelet aggregation via binding to the glycoprotein (GP) IIb/IIIa receptor, were studied, IC50 value of FK633 against platelet aggregation ex vivo induced by 2.5 microM adenosine diphosphate (ADP) was 5.4 x 10(-7) M as determined using hamster platelet rich plasma. The inhibitory effect was also investigated in vivo on thrombus formation at the carotid arterial wall injured by a modified catheter. As a control, the left carotid artery was injured and the time required to develop a thrombotic occlusion (3.9 +/- 1.1 min, mean +/- S.E.M., n = 18) was determined. Then, the right carotid artery of the same animal was injured while a continuous intravenous (i.v.) infusion of FK633 was administered at doses of 0 (saline), 0.1, 0.3 or 1.0 mg/kg/h. The time to occlusion was dose-dependently prolonged. In a separate experiment, 10% of the total tPA dose (0.52 mg/kg) was injected into the injured artery as a bolus and the remaining was infused i.v. at a constant rate for 30 min. When FK633 (0.3 or 1.0 mg/kg/h) was infused together with tPA, late Patency of the reperfused artery was much improved as compared with that of treatment with tPA alone. Bleeding time, measured at the end of the tPA infusion, was markedly prolonged when the higher dose of FK633 (1.0 mg/kg/h) was coadministered, however coadministration of the lower dose of FK633 (0.3 mg/kg/h) was almost without prolongation on the bleeding time, despite a significant effect on the Vascular Patency after thrombolysis. Next, neointima formation was evaluated 2 weeks after the Vascular injury. When FK633 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 3, 7 or 14 days after the Vascular injury, the neointimal area formation was significantly suppressed in the treatment groups for 7 or 14 days. These findings suggest that FK633 inhibits platelet activation in the injured artery and improves Vascular Patency after thrombolysis with tPA with a concomitant suppression of neointima formation.
John J Ricotta - One of the best experts on this subject based on the ideXlab platform.
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failure of thrombolytic therapy to improve long term Vascular Patency
Journal of Vascular Surgery, 1994Co-Authors: Gian Luca Faggioli, Richard M Peer, L Pedrini, Marco Donato Di Paola, James A Upson, M Daddato, John J RicottaAbstract:Abstract Purpose: Few data are available on long-term follow-up of arterial segments subjected to thrombolysis. We reviewed all cases of Vascular occlusion treated with urokinase to identify early success and determine the influence of postlysis intervention and the nature of the thrombosed segment (i.e., artery vs graft) on long-term Patency. Methods: Data on 134 cases (58 arteries, 76 grafts) treated with high-dose urokinase infusion in the lower limbs over a 7-year period were analyzed. Limbs were divided into five groups on the basis of therapy after lytic infusion to determine long-term efficacy: group I, success with no additional therapy; group II, percutaneous angioplasty alone; group III, limited surgical procedure (operative angioplasty, jump graft); group IV, extensive procedure (new bypass); and group V, reVascularization after lytic failure. Long-term results were assessed by life-table analysis and groups compared by log-rank test (Mantel-Haenszel). Results: Initial Patency was established in 87 (64.9%) of 134 cases with 5 deaths (3.7%), 11 amputations (8.2%), and 16 complications (11.9%). Follow-up was available in 68.6% of cases for a mean of 10.9 months. No difference was seen between grafts and native arteries. Patency was analyzed at 6, 12, 18, and 24 months. The 24-month Patency rate after lysis alone (group I - 25.9%) was inferior ( p p > 0.25). Conclusions: Operative intervention is required to produce long-term arterial Patency, even after successful thrombolysis. No statistically significant benefit of thrombolysis on Vascular Patency was seen in our series. (J VASC SURG 1994;19:289-97.)
Hiroyuki Matsuno - One of the best experts on this subject based on the ideXlab platform.
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Plasmin generation plays different roles in the formation and removal of arterial and venous thrombus in mice.
Thrombosis and Haemostasis, 2017Co-Authors: Hiroyuki Matsuno, Osamu Kozawa, Kiyotaka Okada, Shigeru Ueshima, Osamu Matsuo, Toshihiko UematsuAbstract:The role of plasminogen (Plg) and α2-antiplasmin (α2-AP) in Vascular thrombolysis in vivo was investigated in mice deficient in plasminogen (Plg -/-) or α2-AP (α2-AP -/-) or their wild type (PAI-1 +/+, α2- AP +/+). A thrombus was induced in the murine carotid artery or the internal jugular vein by endothelial injury. Blood flow was continuously monitored for 90 min and for 6 h 30 min after the initiation of endothelial injury. The times to occlusion by the developing thrombus in the carotid artery and the jugular vein of wild type mice were 12 ± 1.8 and 7.2 ± 1.9 min, respectively. The arterial thrombus formation in α2- AP -/- mice was indistinguishable from the one in wild type mice, whereas the time to occlusion in Plg -/- was significantly shortened to 5.9 ± 1.7 min. Vascular Patency after spontaneous reperfusion was markedly improved in α2-AP -/- mice. On the contrary, arterial Patency in Plg -/- mice was aggravated. In venous thrombus formation, the time to occlusion in α2-AP -/- mice was significantly prolonged (27.1 ± 5.2 min), whereas in Plg -/- it was slightly shortened to 6.5 ± 2.5 min. Vascular Patency after spontaneous reperfusion was also improved in α2-AP -/- mice, but not in Plg -/- mice. Histological observations using SEM indicated that fibrin nets were firmly fixed on the injured area in Plg -/- mice, but not in α2-AP -/- mice. The tail bleeding time was not different in any type of mice. However, re-bleeding time using a template bleeding device was significantly prolonged in α2-AP -/- as compared with that of wild type mice. In conclusion, lack of plasminogen markedly reduces the antithrombotic activities in vivo, whereas α2-AP plays a more important role in the formation and removal of venous thrombus in mice. Consequently, the inhibition of α2-AP could be a useful tool for the therapy of venous thrombosis and the prevention of re-thrombus formation.
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Effect of GR144053, a fibrinogen-receptor antagonist, on thrombus formation and Vascular Patency after thrombolysis by tPA in the injured carotid artery of the hamster.
Journal of Cardiovascular Pharmacology, 1998Co-Authors: Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Kumiko Tanabe, Motoi Nishida, Hidehiko Hayashi, Toshihiko UematsuAbstract:: The antithrombotic effect of GR144053, which inhibits platelet aggregation by binding to the fibrinogen receptor (glycoprotein IIb/IIIa), was investigated in vitro and in vivo by using hamsters. This compound inhibited the platelet aggregation induced by adenosine diphosphate (ADP; 2.5 microM) with a mean inhibitory concentration (IC50) value of 2.2 +/- 0.4 x 10(-5) M. Vascular injury was inflicted in one carotid artery by using a modified catheter to produce endothelial denudation. In the control group, arterial blood flow was interrupted 4.4 +/- 2.3 min (n = 12) after the injury. When GR144053 continuously infused intravenously at doses of 0 (saline) 0.1, 0.3, and 1.0 mg/kg/h (n = 8, each), the time that elapsed before the vessel became completely obstructed was prolonged in a dose-dependent manner. In separate experiments, reperfusion could be obtained by continuous infusion of tissue-type plasminogen activator (tPA; 0.52 mg/kg) starting 30 min after the initiation of thrombus formation. When GR144053 (0.3 and 1.0 mg/kg/h) was infused in addition to tPA, the incidence of reperfusion and the later Patency of the reperfused artery were much improved as compared with tPA alone. The bleeding time at the end of tPA infusion was significantly prolonged in the presence of the highest dose of GR144053. Next, neointima formation was evaluated 2 weeks after the Vascular injury. When GR144053 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 14 days, the neointimal area was significantly reduced. In separate hamsters, the proliferating index of smooth muscle cells (SMCs) by using bromodeoxyuridine (BrdU) was investigated, and treatment with both tPA and GR144053 significantly decreased the SMC proliferation index in vivo. However, in the in vitro experiments using a hamster SMC line, GR144053 did not have an inhibitory effect on SMC proliferation. These findings suggest that GR144053 inhibits platelet activation on the injured artery and improves Vascular Patency after thrombolysis with tPA, which furthermore results in suppression of neointima formation.
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antiplatelet effect of fk633 a platelet glycoprotein iib iiia antagonist on thrombus formation and Vascular Patency after thrombolysis in the injured hamster carotid artery
Thrombosis and Haemostasis, 1997Co-Authors: Takehiro Kaida, Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Hideo Miyata, Toshihiko UematsuAbstract:: The antithrombotic and restenosis-preventing effects of FK633, an inhibitor of platelet aggregation via binding to the glycoprotein (GP) IIb/IIIa receptor, were studied, IC50 value of FK633 against platelet aggregation ex vivo induced by 2.5 microM adenosine diphosphate (ADP) was 5.4 x 10(-7) M as determined using hamster platelet rich plasma. The inhibitory effect was also investigated in vivo on thrombus formation at the carotid arterial wall injured by a modified catheter. As a control, the left carotid artery was injured and the time required to develop a thrombotic occlusion (3.9 +/- 1.1 min, mean +/- S.E.M., n = 18) was determined. Then, the right carotid artery of the same animal was injured while a continuous intravenous (i.v.) infusion of FK633 was administered at doses of 0 (saline), 0.1, 0.3 or 1.0 mg/kg/h. The time to occlusion was dose-dependently prolonged. In a separate experiment, 10% of the total tPA dose (0.52 mg/kg) was injected into the injured artery as a bolus and the remaining was infused i.v. at a constant rate for 30 min. When FK633 (0.3 or 1.0 mg/kg/h) was infused together with tPA, late Patency of the reperfused artery was much improved as compared with that of treatment with tPA alone. Bleeding time, measured at the end of the tPA infusion, was markedly prolonged when the higher dose of FK633 (1.0 mg/kg/h) was coadministered, however coadministration of the lower dose of FK633 (0.3 mg/kg/h) was almost without prolongation on the bleeding time, despite a significant effect on the Vascular Patency after thrombolysis. Next, neointima formation was evaluated 2 weeks after the Vascular injury. When FK633 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 3, 7 or 14 days after the Vascular injury, the neointimal area formation was significantly suppressed in the treatment groups for 7 or 14 days. These findings suggest that FK633 inhibits platelet activation in the injured artery and improves Vascular Patency after thrombolysis with tPA with a concomitant suppression of neointima formation.
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Antiplatelet effect of FK633, a platelet glycoprotein IIb/IIIa antagonist, on thrombus formation and Vascular Patency after thrombolysis in the injured hamster carotid artery.
Thrombosis and Haemostasis, 1997Co-Authors: Takehiro Kaida, Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Hideo Miyata, Toshihiko UematsuAbstract:: The antithrombotic and restenosis-preventing effects of FK633, an inhibitor of platelet aggregation via binding to the glycoprotein (GP) IIb/IIIa receptor, were studied, IC50 value of FK633 against platelet aggregation ex vivo induced by 2.5 microM adenosine diphosphate (ADP) was 5.4 x 10(-7) M as determined using hamster platelet rich plasma. The inhibitory effect was also investigated in vivo on thrombus formation at the carotid arterial wall injured by a modified catheter. As a control, the left carotid artery was injured and the time required to develop a thrombotic occlusion (3.9 +/- 1.1 min, mean +/- S.E.M., n = 18) was determined. Then, the right carotid artery of the same animal was injured while a continuous intravenous (i.v.) infusion of FK633 was administered at doses of 0 (saline), 0.1, 0.3 or 1.0 mg/kg/h. The time to occlusion was dose-dependently prolonged. In a separate experiment, 10% of the total tPA dose (0.52 mg/kg) was injected into the injured artery as a bolus and the remaining was infused i.v. at a constant rate for 30 min. When FK633 (0.3 or 1.0 mg/kg/h) was infused together with tPA, late Patency of the reperfused artery was much improved as compared with that of treatment with tPA alone. Bleeding time, measured at the end of the tPA infusion, was markedly prolonged when the higher dose of FK633 (1.0 mg/kg/h) was coadministered, however coadministration of the lower dose of FK633 (0.3 mg/kg/h) was almost without prolongation on the bleeding time, despite a significant effect on the Vascular Patency after thrombolysis. Next, neointima formation was evaluated 2 weeks after the Vascular injury. When FK633 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 3, 7 or 14 days after the Vascular injury, the neointimal area formation was significantly suppressed in the treatment groups for 7 or 14 days. These findings suggest that FK633 inhibits platelet activation in the injured artery and improves Vascular Patency after thrombolysis with tPA with a concomitant suppression of neointima formation.
Osamu Kozawa - One of the best experts on this subject based on the ideXlab platform.
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Plasmin generation plays different roles in the formation and removal of arterial and venous thrombus in mice.
Thrombosis and Haemostasis, 2017Co-Authors: Hiroyuki Matsuno, Osamu Kozawa, Kiyotaka Okada, Shigeru Ueshima, Osamu Matsuo, Toshihiko UematsuAbstract:The role of plasminogen (Plg) and α2-antiplasmin (α2-AP) in Vascular thrombolysis in vivo was investigated in mice deficient in plasminogen (Plg -/-) or α2-AP (α2-AP -/-) or their wild type (PAI-1 +/+, α2- AP +/+). A thrombus was induced in the murine carotid artery or the internal jugular vein by endothelial injury. Blood flow was continuously monitored for 90 min and for 6 h 30 min after the initiation of endothelial injury. The times to occlusion by the developing thrombus in the carotid artery and the jugular vein of wild type mice were 12 ± 1.8 and 7.2 ± 1.9 min, respectively. The arterial thrombus formation in α2- AP -/- mice was indistinguishable from the one in wild type mice, whereas the time to occlusion in Plg -/- was significantly shortened to 5.9 ± 1.7 min. Vascular Patency after spontaneous reperfusion was markedly improved in α2-AP -/- mice. On the contrary, arterial Patency in Plg -/- mice was aggravated. In venous thrombus formation, the time to occlusion in α2-AP -/- mice was significantly prolonged (27.1 ± 5.2 min), whereas in Plg -/- it was slightly shortened to 6.5 ± 2.5 min. Vascular Patency after spontaneous reperfusion was also improved in α2-AP -/- mice, but not in Plg -/- mice. Histological observations using SEM indicated that fibrin nets were firmly fixed on the injured area in Plg -/- mice, but not in α2-AP -/- mice. The tail bleeding time was not different in any type of mice. However, re-bleeding time using a template bleeding device was significantly prolonged in α2-AP -/- as compared with that of wild type mice. In conclusion, lack of plasminogen markedly reduces the antithrombotic activities in vivo, whereas α2-AP plays a more important role in the formation and removal of venous thrombus in mice. Consequently, the inhibition of α2-AP could be a useful tool for the therapy of venous thrombosis and the prevention of re-thrombus formation.
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Effect of GR144053, a fibrinogen-receptor antagonist, on thrombus formation and Vascular Patency after thrombolysis by tPA in the injured carotid artery of the hamster.
Journal of Cardiovascular Pharmacology, 1998Co-Authors: Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Kumiko Tanabe, Motoi Nishida, Hidehiko Hayashi, Toshihiko UematsuAbstract:: The antithrombotic effect of GR144053, which inhibits platelet aggregation by binding to the fibrinogen receptor (glycoprotein IIb/IIIa), was investigated in vitro and in vivo by using hamsters. This compound inhibited the platelet aggregation induced by adenosine diphosphate (ADP; 2.5 microM) with a mean inhibitory concentration (IC50) value of 2.2 +/- 0.4 x 10(-5) M. Vascular injury was inflicted in one carotid artery by using a modified catheter to produce endothelial denudation. In the control group, arterial blood flow was interrupted 4.4 +/- 2.3 min (n = 12) after the injury. When GR144053 continuously infused intravenously at doses of 0 (saline) 0.1, 0.3, and 1.0 mg/kg/h (n = 8, each), the time that elapsed before the vessel became completely obstructed was prolonged in a dose-dependent manner. In separate experiments, reperfusion could be obtained by continuous infusion of tissue-type plasminogen activator (tPA; 0.52 mg/kg) starting 30 min after the initiation of thrombus formation. When GR144053 (0.3 and 1.0 mg/kg/h) was infused in addition to tPA, the incidence of reperfusion and the later Patency of the reperfused artery were much improved as compared with tPA alone. The bleeding time at the end of tPA infusion was significantly prolonged in the presence of the highest dose of GR144053. Next, neointima formation was evaluated 2 weeks after the Vascular injury. When GR144053 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 14 days, the neointimal area was significantly reduced. In separate hamsters, the proliferating index of smooth muscle cells (SMCs) by using bromodeoxyuridine (BrdU) was investigated, and treatment with both tPA and GR144053 significantly decreased the SMC proliferation index in vivo. However, in the in vitro experiments using a hamster SMC line, GR144053 did not have an inhibitory effect on SMC proliferation. These findings suggest that GR144053 inhibits platelet activation on the injured artery and improves Vascular Patency after thrombolysis with tPA, which furthermore results in suppression of neointima formation.
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antiplatelet effect of fk633 a platelet glycoprotein iib iiia antagonist on thrombus formation and Vascular Patency after thrombolysis in the injured hamster carotid artery
Thrombosis and Haemostasis, 1997Co-Authors: Takehiro Kaida, Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Hideo Miyata, Toshihiko UematsuAbstract:: The antithrombotic and restenosis-preventing effects of FK633, an inhibitor of platelet aggregation via binding to the glycoprotein (GP) IIb/IIIa receptor, were studied, IC50 value of FK633 against platelet aggregation ex vivo induced by 2.5 microM adenosine diphosphate (ADP) was 5.4 x 10(-7) M as determined using hamster platelet rich plasma. The inhibitory effect was also investigated in vivo on thrombus formation at the carotid arterial wall injured by a modified catheter. As a control, the left carotid artery was injured and the time required to develop a thrombotic occlusion (3.9 +/- 1.1 min, mean +/- S.E.M., n = 18) was determined. Then, the right carotid artery of the same animal was injured while a continuous intravenous (i.v.) infusion of FK633 was administered at doses of 0 (saline), 0.1, 0.3 or 1.0 mg/kg/h. The time to occlusion was dose-dependently prolonged. In a separate experiment, 10% of the total tPA dose (0.52 mg/kg) was injected into the injured artery as a bolus and the remaining was infused i.v. at a constant rate for 30 min. When FK633 (0.3 or 1.0 mg/kg/h) was infused together with tPA, late Patency of the reperfused artery was much improved as compared with that of treatment with tPA alone. Bleeding time, measured at the end of the tPA infusion, was markedly prolonged when the higher dose of FK633 (1.0 mg/kg/h) was coadministered, however coadministration of the lower dose of FK633 (0.3 mg/kg/h) was almost without prolongation on the bleeding time, despite a significant effect on the Vascular Patency after thrombolysis. Next, neointima formation was evaluated 2 weeks after the Vascular injury. When FK633 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 3, 7 or 14 days after the Vascular injury, the neointimal area formation was significantly suppressed in the treatment groups for 7 or 14 days. These findings suggest that FK633 inhibits platelet activation in the injured artery and improves Vascular Patency after thrombolysis with tPA with a concomitant suppression of neointima formation.
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Antiplatelet effect of FK633, a platelet glycoprotein IIb/IIIa antagonist, on thrombus formation and Vascular Patency after thrombolysis in the injured hamster carotid artery.
Thrombosis and Haemostasis, 1997Co-Authors: Takehiro Kaida, Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Hideo Miyata, Toshihiko UematsuAbstract:: The antithrombotic and restenosis-preventing effects of FK633, an inhibitor of platelet aggregation via binding to the glycoprotein (GP) IIb/IIIa receptor, were studied, IC50 value of FK633 against platelet aggregation ex vivo induced by 2.5 microM adenosine diphosphate (ADP) was 5.4 x 10(-7) M as determined using hamster platelet rich plasma. The inhibitory effect was also investigated in vivo on thrombus formation at the carotid arterial wall injured by a modified catheter. As a control, the left carotid artery was injured and the time required to develop a thrombotic occlusion (3.9 +/- 1.1 min, mean +/- S.E.M., n = 18) was determined. Then, the right carotid artery of the same animal was injured while a continuous intravenous (i.v.) infusion of FK633 was administered at doses of 0 (saline), 0.1, 0.3 or 1.0 mg/kg/h. The time to occlusion was dose-dependently prolonged. In a separate experiment, 10% of the total tPA dose (0.52 mg/kg) was injected into the injured artery as a bolus and the remaining was infused i.v. at a constant rate for 30 min. When FK633 (0.3 or 1.0 mg/kg/h) was infused together with tPA, late Patency of the reperfused artery was much improved as compared with that of treatment with tPA alone. Bleeding time, measured at the end of the tPA infusion, was markedly prolonged when the higher dose of FK633 (1.0 mg/kg/h) was coadministered, however coadministration of the lower dose of FK633 (0.3 mg/kg/h) was almost without prolongation on the bleeding time, despite a significant effect on the Vascular Patency after thrombolysis. Next, neointima formation was evaluated 2 weeks after the Vascular injury. When FK633 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 3, 7 or 14 days after the Vascular injury, the neointimal area formation was significantly suppressed in the treatment groups for 7 or 14 days. These findings suggest that FK633 inhibits platelet activation in the injured artery and improves Vascular Patency after thrombolysis with tPA with a concomitant suppression of neointima formation.
Gian Luca Faggioli - One of the best experts on this subject based on the ideXlab platform.
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failure of thrombolytic therapy to improve long term Vascular Patency
Journal of Vascular Surgery, 1994Co-Authors: Gian Luca Faggioli, Richard M Peer, L Pedrini, Marco Donato Di Paola, James A Upson, M Daddato, John J RicottaAbstract:Abstract Purpose: Few data are available on long-term follow-up of arterial segments subjected to thrombolysis. We reviewed all cases of Vascular occlusion treated with urokinase to identify early success and determine the influence of postlysis intervention and the nature of the thrombosed segment (i.e., artery vs graft) on long-term Patency. Methods: Data on 134 cases (58 arteries, 76 grafts) treated with high-dose urokinase infusion in the lower limbs over a 7-year period were analyzed. Limbs were divided into five groups on the basis of therapy after lytic infusion to determine long-term efficacy: group I, success with no additional therapy; group II, percutaneous angioplasty alone; group III, limited surgical procedure (operative angioplasty, jump graft); group IV, extensive procedure (new bypass); and group V, reVascularization after lytic failure. Long-term results were assessed by life-table analysis and groups compared by log-rank test (Mantel-Haenszel). Results: Initial Patency was established in 87 (64.9%) of 134 cases with 5 deaths (3.7%), 11 amputations (8.2%), and 16 complications (11.9%). Follow-up was available in 68.6% of cases for a mean of 10.9 months. No difference was seen between grafts and native arteries. Patency was analyzed at 6, 12, 18, and 24 months. The 24-month Patency rate after lysis alone (group I - 25.9%) was inferior ( p p > 0.25). Conclusions: Operative intervention is required to produce long-term arterial Patency, even after successful thrombolysis. No statistically significant benefit of thrombolysis on Vascular Patency was seen in our series. (J VASC SURG 1994;19:289-97.)
