title: No Effect of Rapamycin on Cardiac Adhesion Formation: A Drug-Loaded Bioresorbable Polylactone Patch in a Porcine Cardiac Surgical Model.
abstract: BACKGROUND
  The fusing of the epicardium and sternum due to adhesion is a common problem during repeated cardiac surgery and carries with it an increased risk of bleeding. The use of barriers and patches has been tested to prevent the formation of adhesions, but the very presence of a patch can provoke adhesion formation. The objective of this study was, therefore, to investigate both biodegradable and bioresorbable polylactone patches [(polycaprolactone-poly(ethylene oxide)-polycaprolactone tri-block copolymer (PCE)]. The patches were also tested with a controlled release of rapamycin, which prevents cell migration and extracellular matrix deposition. The clinical effectiveness of rapamycin in pericardial patches has not previously been examined.
  
  
  METHODS
  Three groups of 6 female Danish Landrace pigs underwent sternotomy and abrasion of the epicardium, before being randomized to either group 1--the control group (with no patch), group 2--PCE patch implanted between the sternum and epicardium, or group 3--PCE patch and slow-release 1.6-mg rapamycin. After a median time period of 26 days, the pigs were euthanized and their hearts removed en bloc with the sternum, for macroscopic, histological and pathological examination.
  
  
  RESULTS
  Upon macroscopic examination, a significantly lower degree of adhesion in group 2, as compared to group 1 (p < 0.05), was found. Histological analysis of the tissues showed significantly more fibrosis, inflammation and foreign body granulomas (p < 0.05) in both group 2 and group 3, when compared to group 1.
  
  
  CONCLUSIONS
  A PCE patch following sternotomy in animal subjects reduces postoperative macroscopic adhesions without reducing microscopic fibrosis or inflammation. Loading the patch with rapamycin was found not to increase the antifibrotic effect.
authors.affiliation: Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
authors.forename: Saddiq
authors.initials: S
authors.lastname: Qazi
authors.forename: Benedict
authors.initials: B
authors.lastname: Kjaergaard
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Shenguo
authors.initials: S
authors.lastname: Wang
authors.forename: Navee
authors.initials: N
authors.lastname: Zhang
authors.forename: Mogens
authors.initials: M
authors.lastname: Vyberg
authors.forename: Arne
authors.initials: A
authors.lastname: Wøyen
authors.forename: Jan Jesper
authors.initials: JJ
authors.lastname: Andreasen
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D006348:Cardiac Surgical Procedures / Q000379:methods*; D005027:Ethylene Oxide; D005260:Female; D005355:Fibrosis; D007783:Lactones; D008953:Models, Anatomic; D009206:Myocardium / Q000473:pathology; D020123:Sirolimus / Q000494:pharmacology*; D013552:Swine; D000267:Tissue Adhesions / Q000517:prevention & control*
chemical_list: D007783:Lactones; C400421:PLC(20)-b-PEO(44); D005027:Ethylene Oxide; D020123:Sirolimus