Prostacyclin analogue iloprost decreases thrombolytic potential of tissue-type plasminogen activator in canine coronary thrombosis.

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Nicolini FA, Mehta JL, Nichols WW, Saldeen TG, Grant M

Prostacyclin analogue iloprost decreases thrombolytic potential of tissue-type plasminogen activator in canine coronary thrombosis.

Circulation. 1990 Mar;81(3):1115-22.

PubMed ID

1689620 [ View in PubMed

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Abstract

Platelets play an important role in the formation of a coronary thrombus and reocclusion after thrombolysis. Therefore, we examined the thrombolytic potential of concomitant intravenous administration of potent platelet inhibitor iloprost, a prostacyclin analogue, with tissue-type plasminogen activator (t-PA; n = 8) and t-PA alone (n = 9) in dogs with an electrically induced occlusive coronary artery thrombus. t-PA (0.75 mg/kg) was given over 20 minutes, and iloprost (4 micrograms/kg) was given over 40 minutes. Reperfusion rate was 63% (five of eight dogs) in the t-PA plus iloprost group and 67% (six of nine dogs) in the t-PA alone group (p = NS). The time to thrombolysis (or reperfusion) in the t-PA plus iloprost group was almost twice as great as in the t-PA alone group (33.0 +/- 13.3 vs. 18.5 +/- 6.7 minutes, mean +/- SD, p less than 0.02), and the duration of reperfusion was much shorter (3.4 +/- 1.8 vs. 39.3 +/- 17.4 minutes, p less than 0.005). Peak coronary artery blood flow after reperfusion in the t-PA plus iloprost group was also less (20 +/- 17 ml/min) than in the t-PA alone group (58 +/- 21 ml/min, p less than 0.005). Reocclusion occurred in all dogs given t-PA with iloprost despite potent synergistic platelet inhibitory effects of t-PA and iloprost, whereas four of six dogs given t-PA alone reoccluded. Neither regimen exerted a significant beneficial effect on regional myocardial shortening during coronary reperfusion. Plasma levels of t-PA were lower when iloprost was given with t-PA (1,022 +/- 360 vs. 1,459 +/- 270 ng/ml in t-PA alone group, p less than 0.05). The detrimental effects of iloprost identified in this study may relate to the reduction in plasma t-PA concentrations by its degradation in the liver caused by the prostacyclin analogue iloprost.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Iloprost	Tissue-type plasminogen activator	Protein	Humans	Unknown	Other/unknown	Details

Drug Interactions

Drugs	Interaction
Integrate drug-drug interactions in your software
Treprostinil Alteplase	The risk or severity of adverse effects can be increased when Alteplase is combined with Treprostinil.
Treprostinil Urokinase	The risk or severity of adverse effects can be increased when Urokinase is combined with Treprostinil.
Treprostinil Reteplase	The risk or severity of adverse effects can be increased when Reteplase is combined with Treprostinil.
Treprostinil Anistreplase	The risk or severity of adverse effects can be increased when Anistreplase is combined with Treprostinil.
Treprostinil Tenecteplase	The risk or severity of adverse effects can be increased when Tenecteplase is combined with Treprostinil.