Inhibition of platelet deposition and lysis of intracoronary thrombus during balloon angioplasty using urokinase-coated hydrogel balloons.
BACKGROUND
Conventional balloon angioplasty of intracoronary thrombus is associated with a high incidence of abrupt closure, distal embolization, and no-reflow phenomenon. The purpose of this study was to assess a new technique for treating intracoronary thrombus consisting of the local delivery of urokinase directly to the angioplasty site with urokinase-coated hydrogel balloons.


RESULTS
We assessed local urokinase delivery using hydrogel balloons in four protocols. First, we evaluated the pharmacokinetics of urokinase delivery in vitro using 125I-labeled urokinase to measure drug loading onto hydrogel balloons, drug retention by the hydrogel polymer during blood exposure, and drug transfer from the balloon surface to the arterial wall during balloon dilatation. Second, we measured 125I-urokinase washoff from the hydrogel balloon in the intact circulation and intramural drug delivery during in vivo balloon angioplasty in 10 anesthetized New Zealand rabbits. Third, we assessed the effect of local urokinase delivery on 111In-labeled platelet deposition after balloon angioplasty in vivo in 13 porcine carotid or iliac arteries dilated with urokinase-coated balloons and compared them with contralateral control arteries dilated with saline-coated balloons. Finally, we determined the clinical efficacy of urokinase-coated balloons in 15 patients with intracoronary thrombus, including 7 who demonstrated abrupt thrombotic closure after conventional angioplasty. Between 241 and 1509 U urokinase could be loaded onto hydrogel balloons ranging in size from 2 to 8 mm. In vitro and in vivo studies demonstrated that hydrogel balloons absorbed significantly more urokinase and demonstrated less drug wash-off than nonhydrogel balloons (P < .01). Similarly, both in vitro and in vivo studies demonstrated urokinase transfer from the hydrogel to the arterial wall during balloon angioplasty, with greater intramural drug deposition with larger balloons (P < .01). Local urokinase delivery after in vivo porcine angioplasty decreased 111In-labeled platelet deposition by 47% compared with contralateral control vessels (P = .03). Use of urokinase-coated balloons in patients with intracoronary thrombus resulted in thrombus dissolution and reversal of abrupt closure in all cases, without evidence of distal embolization.


CONCLUSIONS
With the use of hydrogel-coated balloons, urokinase can be delivered locally to an angioplasty site. This technique decreases platelet deposition after in vivo balloon angioplasty and is efficacious in treating intracoronary thrombus in patients, including those with abrupt thrombotic closure.
Mitchel
J F
JF
Department of Internal Medicine, Hartford Hospital, University of Connecticut 06115.
Azrin
M A
MA
Fram
D B
DB
Hong
M K
MK
Wong
S C
SC
Barry
J J
JJ
Bow
L M
LM
Curley
T M
TM
Kiernan
F J
FJ
Waters
D D
DD
D000328:Adult; D000368:Aged; D000800:Angioplasty, Balloon / Q000295:instrumentation*; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000628:therapy*; D005260:Female; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011817:Rabbits; D013552:Swine; D015912:Thrombolytic Therapy / Q000379:methods*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D014568:Urokinase-Type Plasminogen Activator