Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term

Background. Radial artery bypass conduits are prone to early vasospasm or " string sign" with use of vasopressor therapy intraoperatively and postopera tively, causing increased resistance in coronary artery grafts. Current int raoperative treatment with papaverine fails to provide sustained inhibition of vasoconstriction. We tested the hypothesis that a 30-minute pretreatmen t of radial artery segments with the alpha -adrenergic antagonist phenoxybe nzamine (PB) or the putative protein phosphatase 2,3-butadione monoxime (BD M) attenuates vasoconstriction induced by the vasopressors phenylephrine or norepinephrine for as long as 48 hours compared with papaverine. Methods. Canine radial arteries were harvested, incubated in control buffer or solutions of papaverine 10(-6) M, BDM 10(-6) M or phenoxybenzamine 10(- 6) M for 30 minutes, washed, and stored in drug-free culture medium for 2, 24, or 48 hours. After storage, constriction was induced by norepinephrine at incremental concentrations ranging from 0.7 to 3.5 mu mol/L or by phenyl ephrine (0.300 to 1.5 mu mol/L) with or without the inhibitors, and the deg ree of vasoconstriction was quantified in organ chambers. Responses to nore pinephrine or phenylephrine were compared to constriction with receptor-ind ependent potassium chloride KC1 (30 mmol/L). Results. Maximum responses to phenylephrine and norepinephrine were compara ble at 2, 24, and 48 hours after harvest in the control group (phenylephrin e: 67% +/- 4%, 62% +/- 6%, 65% +/- 6% of KC1 response; norepinephrine: 75% +/- 4%, 62% +/- 1%, 58% +/- 7%, respectively). Papaverine failed to attenua te constriction to phenylephrine and norepinephrine 2, 24, or 48 hours post treatment. Pretreatment with BDM did not reduce vasoconstriction responses to phenylephrine or norepinephrine 2 hours after incubation but did reduce constriction responses thereafter. In contrast, phenoxybenzamine completely attenuated constriction to both phenylephrine (19% +/- 8%,1% +/- 4%, -12% +/- 4%) and norepinephrine (7.1% +/- 1%, -5% +/- 5%, -20% +/- 5%) at 2, 24, and 48 hours posttreatment, respectively. Phenoxybenzamine did not alter e ndothelial function relative to controls at any time point. Conclusions. Thirty-minute pretreatment of RA conduits with 10(-6) M phenox ybenzamine completely inhibits vasoconstriction to phenylephrine and norepi nephrine for as long as 48 hours. Soaking radial artery grafts briefly in p henoxybenzamine solution before implantation may be effective in preventing postoperative vasospasm caused by two common alpha -adrenergic agonists us ed in postoperative hemodynamic management. (C) 2001 by The Society of Thor acic Surgeons.