title: Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term.
abstract: BACKGROUND
  Radial artery bypass conduits are prone to early vasospasm or "string sign" with use of vasopressor therapy intraoperatively and postoperatively, causing increased resistance in coronary artery grafts. Current intraoperative treatment with papaverine fails to provide sustained inhibition of vasoconstriction. We tested the hypothesis that a 30-minute pretreatment of radial artery segments with the alpha-adrenergic antagonist phenoxybenzamine (PB) or the putative protein phosphatase 2,3-butadione monoxime (BDM) 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 micromol/L or by phenylephrine (0.300 to 1.5 micromol/L) with or without the inhibitors, and the degree of vasoconstriction was quantified in organ chambers. Responses to norepinephrine or phenylephrine were compared to constriction with receptor-independent potassium chloride KC1 (30 mmol/L).
  
  
  RESULTS
  Maximum responses to phenylephrine and norepinephrine were comparable at 2, 24, and 48 hours after harvest in the control group (phenylephrine: 67% +/- 4%, 62% +/- 6%, 65% +/- 6% of KC1 response; norepinephrine: 75% +/- 4%, 62% +/- 1%, 58% +/- 7%, respectively). Papaverine failed to attenuate constriction to phenylephrine and norepinephrine 2, 24, or 48 hours posttreatment. 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 endothelial function relative to controls at any time point.
  
  
  CONCLUSIONS
  Thirty-minute pretreatment of RA conduits with 10(-6) M phenoxybenzamine completely inhibits vasoconstriction to phenylephrine and norepinephrine for as long as 48 hours. Soaking radial artery grafts briefly in phenoxybenzamine solution before implantation may be effective in preventing postoperative vasospasm caused by two common alpha-adrenergic agonists used in postoperative hemodynamic management.
authors.affiliation: Carlyle Fraser Heart Center, Crawford Long Hospital of Emory University, Atlanta, Georgia 30308-2225, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Velez
authors.forename: C D
authors.initials: CD
authors.lastname: Morris
authors.forename: S
authors.initials: S
authors.lastname: Muraki
authors.forename: J M
authors.initials: JM
authors.lastname: Budde
authors.forename: R N
authors.initials: RN
authors.lastname: Otto
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Zhao
authors.forename: R A
authors.initials: RA
authors.lastname: Guyton
authors.forename: J
authors.initials: J
authors.lastname: Vinten-Johansen
mesh_terms: D000818:Animals; D001158:Arteries / Q000637:transplantation*; D001026:Coronary Artery Bypass; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D010208:Papaverine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology*; D017534:Radial Artery / Q000637:transplantation; D014021:Tissue Preservation; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D010643:Phenoxybenzamine; D010208:Papaverine