Abstract
Objectives: This in vitro experimental study aimed to compare the effects of a combined solution of glyceryl trinitrate and verapamil (GV) and papaverine on isolated human LIMA and SV.
Materials and Methods: Isolated segments of LIMA and SV from 14 patients undergoing CABG were cut into 3 mm rings and suspended on wire hooks in organ bath chambers. The rings were stretched to their physiological resting tensions and were then contracted by Norepinephrine (NE) 10-6 M. Cumulative concentrations of either GV or papaverine were applied to the contracted LIMA and SV rings (n = 14 for each) and relaxation responses were recorded. When maximal relaxations were achieved, the vasodilators were washed out of the chambers and NE was reintroduced to the chambers after 1 h to assess the residual relaxing effects of the vasodilators.
Results: GV was more potent compared to papaverine in fully (100%) relaxing both LIMA and SV (-log [half-maximal inhibitory concentration] (pIC50): 6.54 ± 0.10 vs. 4.58 ± 0.05 –log M and 6.35 ± 0.08 vs. 4.62 ± 0.05 –log M; P < 0.001 for both). It also had a faster onset of effect (2.9 ± 0.8 vs. 8.1 ± 1.0 min; P = 0.004 and 2.4 ± 0.6 vs. 8.0 ± 0.09 min; P < 0.001). NE-induced contractions after vasodilator treatment were significantly suppressed compared to the initial contractions in LIMAs treated with either GV or papaverine (0.64 ± 0.05 vs. 0.31 ± 0.04 g and 0.56 ± 0.03 vs. 0.08 ± 0.00 g; P < 0.001 for both), but only in SVs treated with papaverine (0.57 ± 0.02 vs. 0.40 ± 0.06 g; P = 0.014). Residual relaxations in the vessels treated with GV were not significantly different from those treated with papaverine after removing the drugs.
Conclusions: The GV solution represented a potent, rapid-acting, and safe alternative to papaverine for reversal of spasm of LIMA and SV conduits and for inhibition of postoperative spasm in LIMA.
Keywords
Coronary Artery Bypass Spasm Nitroglycerin Verapamil Papaverine
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