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Objectives . The development of intimal hyperplasia and graft failure is an important problem in cardiac surgery. A fundamental process in intimal hyperplasia is the degradation of extracellular matrix by metalloproteases which induces the vascular smooth-muscle cells migration and sets the scene for graft atherosclerosis. This study investigated whether doxycycline, a metalloproteases inhibitor, can prevent the intimal hyperplasia occurrence in cultured human internal mammary artery, thus extending graft patency.  Methods . Segments of internal mammary artery from 20 consecutive patients were prepared and cultured for 2 weeks in serum-supplemented medium (control) or in medium supplemented with 10 −5  M and 10 −6  M doxycycline concentrations. Tissues were fixed, sectioned, and stained, and neointimal thickness was measured by computer-aided image analysis. Further sections were cultured and prepared for gel enzymography to measure the matrix metalloproteinase-2 and -9 levels.  Results . At the end of the culture period, neointimal thickness was significantly ( P  = 0.001) dose-dependently reduced in samples treated with doxycycline when compared with controls. Gelatin enzymography demonstrated a reduction in values for both latent and active forms of metalloproteases.  Conclusions . Doxycycline, in a model of internal mammary artery intimal hyperplasia, has a specific role in inhibiting metalloproteases activity and may prevent graft stenosis.

Doxycycline Prevents Intimal Hyperplasia In Vitro and May Improve Patency of the Internal Thoracic Artery