title: Prevention of arterial graft spasm in rats using a vasodilator-eluting biodegradable nano-scaled fibre.
abstract: OBJECTIVE
  Arterial graft spasm occasionally causes circulatory collapse immediately following coronary artery bypass graft. The aim of this study is to evaluate the efficacy of our developed materials, which were composed of milrinone (phosphodiesterase III inhibitor) or diltiazem (calcium-channel blocker), with nano-scaled fibre made of biodegradable polymer to prevent arterial spasm.
  
  
  METHODS
  Milrinone- or diltiazem-releasing biodegradable nano-scaled fibres were fabricated by an electrospinning procedure. In vivo milrinone- or diltiazem-releasing tests were performed to confirm the sustained release of the drugs. An in vivo arterial spasm model was established by subcutaneous injection of noradrenalin around the rat femoral artery. Rats were randomly divided into four groups as follows: those that received 5 mg of milrinone-releasing biodegradable nano-scaled fibre (group M, n = 14); 5 mg of diltiazem-releasing biodegradable nano-scaled fibre (group D, n = 12); or those that received fibre without drugs (as a control; group C, n = 14) implanted into the rat femoral artery. In the fourth group, sham operation was performed (group S, n = 10). One day after the implantation, noradrenalin was injected in all groups. The femoral arterial blood flow was measured continuously before and after noradrenalin injection. The maximum blood flow before noradrenalin injection and minimum blood flow after noradrenalin injection were measured.
  
  
  RESULTS
  In vivo drug-releasing test revealed that milrinone-releasing biodegradable nano-scaled fibre released 78% of milrinone and diltiazem-releasing biodegradable nano-scaled fibre released 50% diltiazem on the first day. The ratios of rat femoral artery blood flow after/before noradrenalin injection in groups M (0.74 ± 0.16) and D (0.72 ± 0.05) were significantly higher than those of groups C (0.54 ± 0.09) and S (0.55 ± 0.16) (P < 0.05).
  
  
  CONCLUSIONS
  Noradrenalin-induced rat femoral artery spasm was inhibited by the implantation of milrinone-releasing biodegradable nano-scaled fibre or diltiazem-releasing biodegradable nano-scaled fibre. These results suggested that our materials might be effective for the prevention of arterial graft spasm after coronary artery bypass graft.
authors.affiliation: Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yagami
authors.forename: Aika
authors.initials: A
authors.lastname: Yamawaki-Ogata
authors.forename: Makoto
authors.initials: M
authors.lastname: Satake
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kaneko
authors.forename: Hideki
authors.initials: H
authors.lastname: Oshima
authors.forename: Akihiko
authors.initials: A
authors.lastname: Usui
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ueda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Narita
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D003251:Constriction, Pathologic; D004110:Diltiazem / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005263:Femoral Artery / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020105:Milrinone / Q000008:administration & dosage*; D057139:Nanofibers; D009638:Norepinephrine; D058987:Phosphodiesterase 3 Inhibitors / Q000008:administration & dosage; D011098:Polyglactin 910; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D002121:Calcium Channel Blockers; D004337:Drug Carriers; D058987:Phosphodiesterase 3 Inhibitors; D014665:Vasodilator Agents; D011098:Polyglactin 910; D004110:Diltiazem; D020105:Milrinone; D009638:Norepinephrine
keywords: Diltiazem; Drug delivery system; Electrospinning; Milrinone; Spasm