Combined thrombolytic effects of tissue-plasminogen activator and a fibrinogen-degradation product peptide 6A or iloprost.
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Nichols WW, Nicolini FA, Saldeen TG, Mehta JL
Combined thrombolytic effects of tissue-plasminogen activator and a fibrinogen-degradation product peptide 6A or iloprost.
J Cardiovasc Pharmacol. 1991 Aug;18(2):231-6.
- PubMed ID
- 1717784 [ View in PubMed]
- Abstract
Thrombolytic effects of tissue-type plasminogen activator (t-PA) are limited by in vivo platelet activation and dynamic coronary vasoconstriction. To examine if the concurrent administration of a fibrin(ogen)-degradation product, pentapeptide 6A (Ala-Arg-Pro-Ala-Lys) with t-PA would improve the thrombolytic effects of t-PA, dogs with electrically induced coronary thrombus were given t-PA alone or with peptide 6A. In dogs given t-PA alone (0.75 mg/kg over 20 min), coronary blood flow was restored in 69% of animals (9 of 13 dogs), with a mean time to reflow of 21 +/- 10 min and duration of reflow of 35 +/- 18 min. Reocclusion occurred in 77% of dogs (7 of 9 dogs). With concurrent administration of peptide 6A (200 mumol), coronary venous 6-keto-PGF1 alpha concentrations increased from 221 +/- 71 to 422 +/- 161 pg/ml (p less than 0.05), but not with t-PA given alone. Coronary blood flow was restored in 7 of 11 dogs (reperfusion rate 64%), with mean time to reflow of 17 +/- 7 min and duration of reflow of 35 +/- 15 min. The coronary reocclusion rate was 86%. All these indices of thrombolysis were similar to those in dogs given t-PA alone. In ex vivo experiments, we also demonstrated release of endothelium-derived relaxing factor from canine coronary artery rings in response to peptide 6A. To further examine the role of prostacyclin (PGI2) in thrombolytic response to t-PA, eight other dogs were given t-PA with a PGI2 analog iloprost (100 ng/kg/min for 40 min).(ABSTRACT TRUNCATED AT 250 WORDS)
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Iloprost Tissue-type plasminogen activator Protein Humans UnknownOther/unknownDetails