The effects of angiotensin-converting-enzyme inhibitors on the fibrous envelope around mammary implants.
BACKGROUND
Late capsular contraction around breast implants is one of the most difficult complications to prevent or resolve. The authors studied the mechanisms that control the fibrotic process in an animal model. Using angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonist, the authors previously described a significant reduction in fibrosis in different experimental models.


METHODS
Four groups of six rats each had a mini breast implant, 12 with a smooth surface and 12 with a textured surface. In two groups, the angiotensin-converting enzyme inhibitor enalapril was administered in drinking water, ad libitum, to determine its effect on both implant types. Two control groups were given plain drinking water. Three months postoperatively, all of the rats were killed and the capsule sections were cut and stained with hematoxylin and eosin and Masson's trichrome. Immunolabeling of collagen III and transforming growth factor (TGF)-beta1 was performed using monoclonal antibodies.


RESULTS
Significant differences were found between smooth and textured implants, with a uniformly low inflammatory response found on textured implants. For both surfaces, the enalapril-treated group had a significant reduction of the inflammatory process that was especially marked in the textured implants. Immunostaining for collagen III and TGF-beta1 showed a consistent reduction in both fibrous tissue and cytokine mediator.


CONCLUSIONS
Enalapril lowers the expression of fibrotic mediators, TGF-beta1, inflammatory markers, anti-ED1, anti-collagen III monoclonals, and the periprosthetic fibrosis process. The reduction of TGF-beta1 indicates that the probable main cytokine mediator of the fibrotic cascade is attenuated. This hypothesis may provide the basis for a safe and cheap therapeutic strategy with which to modify the capsular contracture that sometimes affects women with mammary implants.
Zimman
Oscar A
OA
Buenos Aires, Argentina; and Ponce, Puerto Rico From the Division of Plastic Surgery, Department of Surgery, Hospital de Clínicas; Laboratory of Experimental Medicine, Hospital Alemán; Institute of Cardiovascular Research, School of Medicine, University of Buenos Aires; and Department of Physiology and Pharmacology, Ponce School of Medicine.
Toblli
Jorge
J
Stella
Inés
I
Ferder
Marcelo
M
Ferder
Leon
L
Inserra
Felipe
F
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018427:Breast Implants; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D004867:Equipment Design; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control; D015745:Granuloma, Foreign-Body / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D020007:Implants, Experimental; D008321:Mammary Glands, Animal / Q000473:pathology / Q000601:surgery; D011183:Postoperative Complications / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D024061:Collagen Type III; D053773:Transforming Growth Factor beta1; D004656:Enalapril