Thrombolytic potency of acid-stabilized plasmin: superiority over tissue-type plasminogen activator in an in vitro model of catheter-assisted thrombolysis.
Plasmin, the direct fibrinolytic enzyme, was compared with tissue plasminogen activator (t-PA) in an in vitro thrombolysis model. Plasmin has been prepared in a highly pure form from human plasma and has been stabilized against auto-degradation by low-pH formulation. This acidified formulation of plasmin has been designed to have a low buffering capacity so that it can be directly infused into clots in a stable and latently active form. This low-pH formulation has been shown to be equivalent to a neutral-pH formulation of plasmin in its extent of clot lysis. An in vitro model of catheter-assisted thrombolysis has been devised in which large (12 x 0.6 cm), retracted clots are treated with an intrathrombus thrombolytic agent via a multi-sideport catheter. Plasmin dissolves these plasminogen-deficient clots in a dose-dependent manner and is clearly superior to t-PA. In this model system, t-PA exhibits efficacy only when retracted clots are replenished with plasminogen.
Novokhatny
V
V
Bayer Corporation, Biological Products Division, Research Triangle Park, North Carolina 27709, USA. valery.novokhatny.b@bayer.com
Taylor
K
K
Zimmerman
T P
TP
D002404:Catheterization; D003018:Clot Retraction; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005341:Fibrinolysin / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008955:Models, Cardiovascular; D010958:Plasminogen / Q000494:pharmacology; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use
D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin