Dimensão fractal e histometria digital na avaliação dos efeitos do propranolol sobre a reação capsular ao implante de silicone

Abstract

Despite their popular use in breast augmentation and reconstruction surgeries, the limited biocompatibility of silicone implants can induce severe side effects, including adverse capsularcontracture (ACC), an excessive foreign body reaction that forms, by unknown reason, a tight and hard fibrous capsule around the implant. A non-surgical treatment for ACC will be desirable as revision surgery for capsulotomy or capsulectomy with implant exchange are associated with a high risk of recurrence and complications. Recently it has been shown that sympathetic denervation accelerates wound contraction and delays reepithelialization in rats. Another study demonstrated that beta-adrenoceptor blockade has antifibrotic effects in a murine model of nonsinusoidal liver fibrosis. This study examines the effects of using propranolol, a non-selective beta-adrenoceptor antangonist, to prevent capsular formation around texturized silicone prosthesis implanted in the dorsum of male guinea-pigs. Animals (n=36) were randomly distributed into two equal groups, untreated or orally treated with propranololol (10 mg/kg dissolved in daily water). Capsules and implants were removed and examined for inflammation, thickness, fibrosis progression, density of type I and III collagen and fractal dimension by histological scoring using hematoxilin-eosin stained samples, digital histometry for measuring capsular thickness, picrosirius-polarization and digital image analysis for type I and type III collagen density and fractal dimension calculation by box-counting after 7, 14 or 21 days.Propranolol significantly reduced inflammation scores in the capsular tissue as compared to untreated group. Also, the capsular content of type I and type III collagen showed a statistical difference among the groups at different time points (p< 0,0001, Kruskal-Wallis test). The type I collagen density observed at 1, 2 or 3 weeks decreased significantly compared with that found in the control group. Conversely, the density of type III collagen increased in propranolol-treated group along the time.The capsule thickness in propranolol-treated cavies was significantly thinner and exhibited higher collagen type III/type I ratios and more irregular collagen fiber alignments than control animals. The observed decrease in fractal dimension of collagen also supported the alleviation of capsular formation by propranolol usage. Taken together, these data show that propranolol efficiently delays formation (antiproliferative or citotoxity effects) and maturation (antifibrogenic effect) of capsule around textured implants. Therefore, the blockade of beta-adrenoceptors is a promising option to support future therapeutic strategies in the treatment/prevention of capsular contracture.