title: Evaluation of the long-term effectiveness of extraluminal and intraluminal vasodilators in an in vitro porcine model of arterial graft spasm.
abstract: OBJECTIVE
  Postoperative graft spasm is a concern when arterial conduits are used because there may be insufficient arterial graft flow. Intraoperatively, vasodilators are used to increase flow and prevent spasm, but little is known about their duration of effectiveness.
  
  
  METHODS
  To examine this we attached porcine gastroepiploic and internal thoracic arteries (GEA, n = 48; ITA, n = 24, 10-12 cm long) to a computer-controlled perfusion system (constant inflow pressure 80 mm Hg) with a fixed outflow resistance. Norepinephrine (10(-9)-10(-5) M) was incrementally added to the perfusate at baseline (B), then immediately (h+0) and 2 h (h+2) after the vessels were treated with 30 min of extraluminal or intraluminal nitroglycerin, nitroprusside, verapamil or papaverine.
  
  
  RESULTS
  At (B), norepinephrine caused a dose-dependent decrease in flow in both the ITAs and GEAs. In the ITAs, at (h+0), both extraluminal and intraluminal papaverine and, to a lesser extent nitroprusside, increased initial flow and decreased graft sensitivity to norepinephrine. At (h+2), only extraluminal papaverine sustained this maximal effect (ED50 for extraluminal papaverine at (B) 2.6 E(-7) vs. (h+2) 1.3 E(-6), P = 0.01). For the GEAs, at (h+0), both extraluminal and intraluminal verapamil, papaverine, nitroprusside and nitroglycerin attenuated flow reduction due to norepinephrine. At (h+2), only extraluminal papaverine, extraluminal verapamil and intraluminal verapamil were effective in preventing norepinephrine-induced spasm (ED50 for extraluminal papaverine at (B) 1.0 E(-7) vs. (h+2) 6.4 E(-6) (P = 0.004); extraluminal verapamil at (B) 1.2 E(-7) vs. (h+2) 4.0 E(-6); intraluminal verapamil at (B) 5.8 E(-7) vs. (h+2) 5.7 E(-6), P = 0.005).
  
  
  CONCLUSIONS
  Verapamil-and papaverine-treated arteries have a greater duration of efficacy in resisting spasm than arteries treated with nitroglycerin and nitroprusside. In the ITA, extraluminal administration of papaverine is most efficacious, possibly due to the prolonged exposure afforded by this route of administration. The effects of verapamil and papaverine are more prolonged in the GEA when administered extraluminally, potentially due to absorption in the perivascular fat-pad and subsequent slow release. The results of this study suggest that extraluminally administered verapamil and papaverine appear to be the preferred vasodilators for preventing arterial graft spasm in the postoperative period. This may be especially important when multiple arterial grafts are used.
authors.affiliation: Department of Surgery, University of Louisville, Kentucky 40202, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Montgomery
authors.forename: P
authors.initials: P
authors.lastname: Spence
authors.forename: A T
authors.initials: AT
authors.lastname: Ali
authors.forename: J L
authors.initials: JL
authors.lastname: Ballen
authors.forename: C J
authors.initials: CJ
authors.lastname: Riordan
authors.forename: J H
authors.initials: JH
authors.lastname: Storey
authors.forename: W P
authors.initials: WP
authors.lastname: Santamore
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D006083:Graft Occlusion, Vascular / Q000503:physiopathology / Q000517:prevention & control*; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects / Q000503:physiopathology; D009638:Norepinephrine / Q000008:administration & dosage; D010477:Perfusion; D011183:Postoperative Complications; D013552:Swine; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009638:Norepinephrine