RESUMO
BACKGROUND: Probucol reduces restenosis after angioplasty, provided oral administration is begun 1 month before the procedure. Local vascular delivery of a nonoparticulate formulation of probucol may obviate the need for drug loading by acutely raising arterial intramural concentration while providing sustained intramural retention. To test this hypothesis, we compared the retention and redistribution of (35)S-probucol encapsulated in either liposomal or polylactic-coglycolic acid (PLGA) nanoparticles after local vascular delivery. METHODS: Nanoparticles were delivered using a Crescendo microporous infusion catheter (Cordis, Warren, NJ) after balloon angioplasty of rabbit iliac arteries (n = 12-18 arteries per formulation per time point). Animals were euthanized on day 0, 3, or 7 after delivery. Iliac arteries, perivascular fat, and downstream tissues were harvested and the radioactivity disintegrations per minute was measured. Autoradiographic and confocal microscopic analyses of tissue sections were performed to evaluate intramural distribution of probucol. RESULTS: Immediately after delivery, radioactivity in the iliac arteries (log[dpm/mg], mean +/- SEM) was greater with PLGA (2.72 +/- 0.08) than with liposomal encapsulation (2.10 +/- 0.08, P = 0.001). Intramural retention of probucol was 23% at 7 days using liposomes and 10% using PLGA, corresponding to a probucol concentration of 0.1 ng/mg tissue for both formulations. By the third day after delivery, radioactivity in peri-iliac fat, femoral arteries, and hindlimb muscle increased by 88%, 29%, and 154%, respectively. Thereafter, radioactivity decreased to 56%, 43%, and 134% of initial dpm respectively, by day 7. CONCLUSIONS: although delivery efficiency was superior with PLGA encapsulation, intramural probucol concentrations were similar on day 7 using both formulations. Radial and axial redistribution of probucol was observed, indicating that this technique can be exploited to increase adjacent tissue delivery.
RESUMO
Mechanical prosthetic valve thrombosis is a life-threatening complication necessitating immediate intervention. The presenting signs and symptoms of this illness are somewhat variable, but physical examination and transesophageal echocardiography enable rapid diagnosis. To avoid catastrophic complications, valve replacement or debridement, or thrombolysis in the correct setting, must be performed without delay. It is not entirely clear which therapy is superior. For any given patient, the risks of thrombolytic therapy, including bleeding, systemic embolism, and failure to restore valvular function, must be weighed against the risks of surgical intervention. Once the decision is made to operate, the choice of valve replacement versus debridement is one best made intraoperatively, upon visual inspection of the valve apparatus. Despite aggressive therapy, morbidity and mortality from prosthetic valve thrombosis and its treatment are not trivial. Fortunately, with current prosthetic devices and aggressive prophylactic anticoagulation, the incidence of prosthetic valve thrombosis remains low. Antiplatelet therapy may offer additional benefit to patients being prophylaxed with warfarin. This report details the case of a woman with aortic and mitral prosthetic valves who presented with heart failure and evidence of severe aortic prosthetic dysfunction after a period of suboptimal anticoagulation. She successfully underwent debridement of the mitral prosthesis and replacement of the aortic valve. The relevant literature is reviewed.
