Vasodilator pre-treatment of human radial arteries; comparison of effects of phenoxybenzamine vs papaverine on norepinephrine-induced contraction in vitro

AIMS: The radial artery, increasingly used for coronary artery bypass grafting (CABG). has a potential for spasm which may increase peri-operative risk. Increased alpha-adrenoceptor activation is a key candidate for the spasm. We studied the effects of vasoconstriction in a radial artery, which had undergone brief exposure to the alpha-adrenoceptor antagonist phenoxybenzamine vs the opioid derivative papaverine. METHODS AND RESULTS: Using standard classical organ bath techniques, concentration responses were obtained to norepinephrine in segments of radial artery from 12 CABG patients pre- and post-incubation for 20 min in either phenoxybenzamine 10(-6) M or papaverine 3 x 10(-3) M. Responses were reassessed 2, 4 and 18 h after washout of phenoxybenzamine and 2, 4, 8 and 18 h after washout of papaverine. There was concentration-dependent constriction to norepinephrine (maximum response 0.89 +/- 0.20 (SEM) g x mm(-1), n=6). Constriction to norepinephrine was abolished immediately after incubation in phenoxybenzamine and remained completely inhibited for at least 18 h (P<0.0001 ANOVA phenoxybenzamine pre-treated vs controls). Most of the inhibition of concentration-dependent constriction to norepinephrine following pre-treatment with papaverine was lost 8 h later. CONCLUSION: Radial artery vasoconstriction induced by a clinically relevant agonist, norepinephrine, may be prevented for at least 18 h by pre-incubation in phenoxybenzamine, in contrast to the brief inhibition achieved by pre-treatment with papaverine. Adding phenoxybenzamine to radial artery graft bathing solution may improve early outcome following CABG.