Sustained reflow in dogs with coronary thrombosis with K2P, a novel mutant of tissue-plasminogen activator.

Abstract

Coronary artery reocclusion after thrombolysis with human recombinant tissue-type plasminogen activator (rt-PA) is related to the short half-life of this agent in plasma. K2P, a mutant of rt-PA lacking the fibronectin fingerlike, epidermal growth factor-like and first kringle domains (amino acids 6 to 173) and having the glycosylation site Asn184 mutagenized to Gln, has been produced in Chinese hamster ovary cells. In this study we compared the thrombolytic effect of K2P and rt-PA in dogs with electrically induced coronary artery thrombosis. Both agents were given intravenously in equimolar amounts over 20 min after the occlusive thrombus was stable for 30 min; dogs were monitored for 1 h after reperfusion if flow occurred. Coronary blood flow was restored by rt-PA in 6 (60%) of 10 dogs. The restored flow lasted for 49 +/- 12 min and mean flow at 60 min from the start of reperfusion was 7 +/- 3 ml/min. The reocclusion rate was 50% (three of six dogs). Flow was restored in five (100%) of five dogs by K2P. The restored blood flow lasted during the entire 1-h observation period in all but one dog and mean flow at 60 min was 49 +/- 16 ml/min (p less than 0.02 vs. flow in rt-PA-treated dogs). Restored coronary blood flow showed marked cyclic flow variations in rt-PA-treated but not in K2P-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: F A Nicolini, W W Nichols, J L Mehta, T G Saldeen, R Schofield, M Ross, D W Player, G B Pohl, C Mattsson
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 20 Issue 1 Pg. 228-35 (Jul 1992) ISSN: 0735-1097 [Print] United States
• PMID: 1607530 (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

• Plasminogen Inactivators
• Recombinant Proteins
• Tissue Plasminogen Activator

Topics

• Animals
• Coronary Thrombosis (drug therapy)
• Dogs
• Female
• Heart (drug effects)
• Hemodynamics (drug effects)
• Male
• Microscopy, Electron, Scanning
• Plasminogen Inactivators (blood)
• Platelet Aggregation (drug effects)
• Recombinant Proteins (therapeutic use)
• Thrombolytic Therapy
• Tissue Plasminogen Activator (therapeutic use)