Evaluation of the long-term effectiveness of extraluminal and intraluminal vasodilators in an in vitro porcine model of arterial graft spasm

OBJECTIVE: Postoperative graft spasm is a concern when arterial conduitsare 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: Toexamine this we attached porcine gastroepiploic and internal thoracicarteries (GEA, n = 48; ITA, n = 24, 10-12 cm long) to a computer-controlledperfusion system (constant inflow pressure 80 mm Hg) with a fixed outflowresistance. Norepinephrine (10(-9)-10(-5) M) was incrementally added to theperfusate at baseline (B), then immediately (h+0) and 2 h (h+2) after thevessels were treated with 30 min of extraluminal or intraluminalnitroglycerin, nitroprusside, verapamil or papaverine. RESULTS: At (B),norepinephrine caused a dose-dependent decrease in flow in both the ITAsand GEAs. In the ITAs, at (h+0), both extraluminal and intraluminalpapaverine and, to a lesser extent nitroprusside, increased initial flowand decreased graft sensitivity to norepinephrine. At (h+2), onlyextraluminal papaverine sustained this maximal effect (ED50 forextraluminal 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 dueto norepinephrine. At (h+2), only extraluminal papaverine, extraluminalverapamil and intraluminal verapamil were effective in preventingnorepinephrine-induced spasm (ED50 for extraluminal papaverine at (B) 1.0E(-7) vs. (h+2) 6.4 E(-6) (P = 0.004); extraluminal verapamil at (B) 1.2E(-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). CONCLUSION: Verapamil-and papaverine-treatedarteries have a greater duration of efficacy in resisting spasm thanarteries treated with nitroglycerin and nitroprusside. In the ITA,extraluminal administration of papaverine is most efficacious, possibly dueto the prolonged exposure afforded by this route of administration. Theeffects of verapamil and papaverine are more prolonged in the GEA whenadministered extraluminally, potentially due to absorption in theperivascular fat-pad and subsequent slow release. The results of this studysuggest that extraluminally administered verapamil and papaverine appear tobe the preferred vasodilators for preventing arterial graft spasm in thepostoperative period. This may be especially important when multiplearterial grafts are used.