Local delivery of NO-donor molsidomine post-PTA improves haemodynamics, wall mechanics and histomorphometry in atherosclerotic porcine SFA.
OBJECTIVE
we investigated the therapeutic effect of angioplasty with local drug delivery (LDD) of the wall-accumulating NO-donor molsidomine (M) in the superficial femoral arteries (SFA) of atherosclerotic swine.


METHODS
atherosclerotic Pietrin swines (n=14) underwent PTA-LDD-M (4 mg/2 ml) vs contralateral PTA-LDD-Placebo in the SFA using a channelled balloon angioplasty catheter. Invasive and colour Doppler energy (CDE) assessments of haemodynamics and wall mechanics were performed at 24 h (n=4) and 5 months (n=10). Immuno-histolabelling of cell proliferation and histomorphometry were serially performed in perfusion fixed SFA samples.


RESULTS
at 24 h, PCNA-positive nuclei revealed 33+/-14 and 12+/-3 proliferating cells/mm2 at placebo and molsidomine PTA-LDD sites, respectively (p<0.001). At 5 months, PTA-LDD-M vessels, compared with PTA-LDD-P, had increased compliance (66+/-9 vs 11+/-4 ml/mmHg) and lowered impedance (0.11+/-0.05 vs 0.45+/-0.14 mmHg/ml x min(-1)) (p<0.05). CDE revealed low, middle and high velocity peaks at 7.5, 20 and 35, and 8, 15 and 22 cm x s(-1) in systolic and diastolic flows, respectively; and PTA-LDD-M prevented emergence of restenosis-associated increases in low blood velocities (p<0.01). PTA-LDD-M inhibited restenotic intimal thickening and medial thinning which decreased mean lumenal diameter in placebo-treated (2.6+/-0.3) as compared to molsidomine-treated (3.4+/-0.3 mm) vessels (p<0.05).


CONCLUSIONS
in the atherosclerotic porcine SFA model, PTA-LDD with molsidomine consistently improved haemodynamic wall mechanics, lowered cell proliferation and prevented late lumen loss observed with PTA-LDD with placebo.
Rolland
P H
PH
Hemodynamics and Cardiovascular Mechanics Laboratory, School of Medicine, Hôpital La Timone, 27 Bd Jean-Moulin, 13385 Marseille Cedex 5, France.
Bartoli
J M
JM
Piquet
Ph
P
Mekkaoui
C
C
Nott
S H
SH
Moulin
G
G
Amabile
P
P
Mesana
T
T
D000279:Administration, Cutaneous; D000800:Angioplasty, Balloon; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D005263:Femoral Artery / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D011182:Postoperative Care; D013552:Swine; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use
D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D008981:Molsidomine