Combined thrombolytic effects of tissue-plasminogen activator and a fibrinogen-degradation product peptide 6A or iloprost.
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)
Nichols
W W
WW
University of Florida College of Medicine, Department of Medicine, Gainesville.
Nicolini
F A
FA
Saldeen
T G
TG
Mehta
J L
JL
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003328:Coronary Thrombosis / Q000188:drug therapy*; D004285:Dogs; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D016285:Iloprost / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D009569:Nitric Oxide; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D016285:Iloprost