European Journal of Cardio-Thoracic Surgery, Vol 10, 1071-1081, Copyright © 1996 by European Association for Cardio-thoracic Surgery
Evaluation of the long-term effectiveness of extraluminal and intraluminal vasodilators in an in vitro porcine model of arterial graft spasm
WD Montgomery, P Spence, AT Ali, JL Ballen, CJ Riordan, JH Storey and WP Santamore
Department of Surgery, University of Louisville, Kentucky 40202, USA.
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). CONCLUSION: 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.
