Local delivery of a synthetic antithrombin with a hydrogel-coated angioplasty balloon catheter inhibits platelet-dependent thrombosis.
OBJECTIVE
This study evaluated the efficacy of local administration of an antithrombin agent with a hydrogel-coated percutaneous transluminal coronary angioplasty balloon catheter.


BACKGROUND
Intravenous infusion of antithrombin compounds has been shown to inhibit platelet-dependent thrombosis. However, hemorrhage is a common side effect associated with the systemic administration of antithrombin compounds.


METHODS
The potent, irreversible thrombin inhibitor D-Phe-L-Pro-L-Arginyl chloromethyl ketone (PPACK) was used to inhibit thrombus formation in chronic porcine arteriovenous shunts. Platelet deposition was quantitated with gamma camera imaging of 111In-labeled platelets.


RESULTS
Intravenous administration of PPACK in swine, in doses sufficient to maximally inhibit thrombus formation, was associated with prolongation of bleeding parameters. The inhibition of thrombosis associated with intravenous PPACK was dose related. The amount of intravenous PPACK necessary for maximal inhibition of thrombus formation for a period of 45 min was 16.9 mg. In contrast, local delivery of PPACK with a hydrogel-coated angioplasty balloon deployed at the site of the thrombus inhibited platelet deposition for at least 45 min after the balloon was removed. Using 3H-labeled PPACK, the calculated amount of PPACK delivered was 33.5 micrograms. There was no change in bleeding time or activated partial thromboplastin time when swine received an intravenous bolus greater than the total amount of PPACK adsorbed onto the balloon (70 micrograms).


CONCLUSIONS
These results suggest that in this model, a hydrogel-coated coronary angioplasty balloon catheter can be used to deliver enough antithrombin agent to inhibit platelet-dependent thrombosis for at least 45 min at doses that are several orders of magnitude less than those required for systemic administration. In addition, local delivery can provide effective inhibition of thrombus formation without alteration of bleeding parameters.
Nunes
G L
GL
Andreas R. Gruentzig Cardiovascular Center, Emory University Hospital, Atlanta, Georgia 30322.
Hanson
S R
SR
King
S B
SB
Sahatjian
R A
RA
Scott
N A
NA
D000590:Amino Acid Chloromethyl Ketones / Q000008:administration & dosage*; D000800:Angioplasty, Balloon / Q000295:instrumentation*; D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage*; D001792:Blood Platelets / Q000502:physiology; D002404:Catheterization; D003328:Coronary Thrombosis / Q000517:prevention & control*; D016503:Drug Delivery Systems; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007275:Injections, Intravenous; D011092:Polyethylene Glycols; D013552:Swine
D000590:Amino Acid Chloromethyl Ketones; D000991:Antithrombins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone