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


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.


CONCLUSIONS
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.
Harrison
W E
WE
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London, UK.
Mellor
A J
AJ
Clark
J
J
Singer
D R
DR
D000368:Aged; D000704:Analysis of Variance; D001026:Coronary Artery Bypass / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010208:Papaverine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology*; D017534:Radial Artery / Q000187:drug effects* / Q000637:transplantation; D013035:Spasm / Q000517:prevention & control*; D014652:Vascular Diseases / Q000517:prevention & control; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D010643:Phenoxybenzamine; D010208:Papaverine