Pretreatment with phenoxybenzamine attenuates the radial artery's vasoconstrictor response to α-adrenergic stimuli

Background: Although the radial artery bypass conduit has excellent intermediate-term patency, it has a proclivity to vasospasm. We tested the hypothesis that brief pretreatment of a radial artery graft with the irreversible adrenergic antagonist phenoxybenzamine attenuates the vasoconstrictor response to the vasopressors phenylephrine and norepinephrine compared with the currently used papaverine/lidocaine. Methods: Segments of human radial artery grafts were obtained after a 30-minute intraoperative pretreatment with a solution containing 20 mL of heparinized blood, 0.4 mL of papaverine (30 mg/mL), and 1.6 mL of lidocaine (1%). The segments were transported to the laboratory and placed into a bath containing Krebs-Henseleit solution and 10, 100, or 1000 μmol/L phenoxybenzamine or vehicle. The segments were tested in organ chambers for contractile responses to increasing concentrations of phenylephrine and norepinephrine (0.5-15 μmol/L). Results: Contractile responses to 15 μmol/L phenylephrine in control radial artery segments averaged 44.2% ± 9.1% of the maximal contractile response to 30 mmol/L KCl. Papaverine/lidocaine modestly attenuated contraction to 15 μmol/ L phenylephrine (32.1% ± 5.9%; P = .22), but 1000 μmol/L phenoxybenzamine completely abolished radial artery contraction (-7.2% ± 4.4%; P < .001). The effect of 10 and 100 μmol/L phenoxybenzamine on attenuating vasocontraction was intermediate between 1000 μmol/L phenoxybenzamine and papaverine/lidocaine. Responses to 15 μmol/L norepinephrine in control radial artery segments averaged 54.7% ± 7.5% of maximal contraction to 30 mmol/L KCl. Papaverine/lidocaine modestly attenuated the contraction response of radial artery segments (35.6% ± 5.1%; P = .04). In contrast, 1000 μmol/L phenoxybenzamine showed the greatest attenuation of norepinephrine-induced contraction (-10.5% ± 2.0%; P < .001). Conclusions: A brief pretreatment of the human radial artery bypass conduit with 1000 μmol/L phenoxybenzamine completely attenuates the vasoconstrictor responses to the widely used vasopressors norepinephrine and phenylephrine. Papaverine/lidocaine alone did not block vasoconstriction to these α-adrenergic agonists.