Optimization of drug-eluting balloon use for safety and efficacy: evaluation of the 2nd generation paclitaxel-eluting DIOR-balloon in porcine coronary arteries.
OBJECTIVE
The aim of this preclinical study was to optimize the use of drug-eluting balloon (DEB) DIOR(2nd) (generation) by measurements of tissue and plasma paclitaxel concentrations in porcine coronary artery overstretch and prove efficacy in inhibition of neointimal growth without complementary use of stent.


BACKGROUND
The usually recommended DEB 60 sec inflation time causes prolonged ischemia and arterial injury.


METHODS
Tissue, plasma, and balloon surface concentrations of paclitaxel were measured in pigs 45 min and 12 hr after balloon inflation times of 15, 20, 30, 45, and 60 sec. Extent of neointimal hyperplasia was compared using DIOR(2nd) (generation) or noncoated balloon at two-week follow-up. Paclitaxel was replaced by fluorescent paclitaxel derivative in DEB and DES to demonstrate the distribution of the drug in arterial wall.


RESULTS
DIOR(2nd) (generation) DEB provided 29 ± 3 μM/L, 52 ± 6 μM/L, 196 ± 44 μM/L, 202 ± 36 μM/L, and 184 ± 59 μM/L paclitaxel to the vessel wall after 15, 20, 30, 45, and 60 sec of dilation, reaching plateau at 30 sec inflation time. Paclitaxel penetrated up to 2 mm tissue deepness. Measurable plasma paclitaxel level (45 ± 28 ng/mL) was found only after 60 sec balloon inflation time. At follow-up, the dilated arterial segment neointimal area and maximal neointimal thickness were significantly smaller with DIOR vs. uncoated balloon use. Fluorescence images of DIOR showed a homogenous distribution of the drug on the vessel, in contrast with DES.


CONCLUSIONS
Using the DIOR(2nd) (generation) DEB, a maximal balloon inflation time of 30-45 sec is optimal, reducing effectively the neointimal hyperplasia.
Pósa
Anikó
A
Department of Cardiology, Medical University of Vienna, Austria.
Nyolczas
Noemi
N
Hemetsberger
Rayyan
R
Pavo
Noemi
N
Petnehazy
Ors
O
Petrasi
Zsolt
Z
Sangiorgi
Giuseppe
G
Gyöngyösi
Mariann
M
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D049109:Cell Proliferation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004867:Equipment Design; D006965:Hyperplasia; D008422:Materials Testing; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D017239:Paclitaxel / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D034421:Sus scrofa; D014018:Tissue Distribution; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D002317:Cardiovascular Agents; D017239:Paclitaxel