Combined thrombolytic effects of tissue-plasminogen activator and a fibrinogen-degradation product peptide 6A or iloprost.

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)

• Authors: W W Nichols, F A Nicolini, T G Saldeen, J L Mehta
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 18 Issue 2 Pg. 231-6 (Aug 1991) ISSN: 0160-2446 [Print] United States
• PMID: 1717784 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Nitric Oxide
• Epoprostenol
• Tissue Plasminogen Activator
• Iloprost

Topics

• Animals
• Coronary Circulation (drug effects)
• Coronary Thrombosis (drug therapy)
• Dogs
• Drug Therapy, Combination
• Epoprostenol (metabolism)
• Hemodynamics (drug effects)
• Iloprost (therapeutic use)
• Male
• Nitric Oxide (metabolism)
• Tissue Plasminogen Activator (therapeutic use)