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

F. A. Nicolini, J. L. Mehta, W. W. Nichols, T. G.P. Saldeen, M. Grant

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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 μg/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<0.02), and the duration of reperfusion was much shorter (3.4±1.8 vs. 39.3±17.4 minutes, p<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<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< 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.

Original languageEnglish (US)
Pages (from-to)1115-1122
Number of pages8
JournalCirculation
Volume81
Issue number3
DOIs
StatePublished - Mar 1990

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Keywords

  • Iloprost
  • Platelet aggregation
  • Prostacyclin
  • Thrombolysis
  • Tissue-type plasminogen activator

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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