title: Pretreatment with phenoxybenzamine attenuates the radial artery's vasoconstrictor response to alpha-adrenergic stimuli.
abstract: 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 micromol/L phenoxybenzamine or vehicle. The segments were tested in organ chambers for contractile responses to increasing concentrations of phenylephrine and norepinephrine (0.5-15 micromol/L).
  
  
  RESULTS
  Contractile responses to 15 micromol/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 micromol/L phenylephrine (32.1% +/- 5.9%; P =.22), but 1000 micromol/L phenoxybenzamine completely abolished radial artery contraction (-7.2% +/- 4.4%; P <.001). The effect of 10 and 100 micromol/L phenoxybenzamine on attenuating vasocontraction was intermediate between 1000 micromol/L phenoxybenzamine and papaverine/lidocaine. Responses to 15 micromol/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 micromol/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 micromol/L phenoxybenzamine completely attenuates the vasoconstrictor responses to the widely used vasopressors norepinephrine and phenylephrine. Papaverine/lidocaine alone did not block vasoconstriction to these alpha-adrenergic agonists.
authors.affiliation: Cardiothoracic Research Laboratroy, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center at Crawford Long Hospital, Emory University School of Medicine, Atlanta, GA 30308, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Corvera
authors.forename: Cullen D
authors.initials: CD
authors.lastname: Morris
authors.forename: Jason M
authors.initials: JM
authors.lastname: Budde
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Velez
authors.forename: John D
authors.initials: JD
authors.lastname: Puskas
authors.forename: Omar M
authors.initials: OM
authors.lastname: Lattouf
authors.forename: William A
authors.initials: WA
authors.lastname: Cooper
authors.forename: Robert A
authors.initials: RA
authors.lastname: Guyton
authors.forename: Jakob
authors.initials: J
authors.lastname: Vinten-Johansen
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D016022:Case-Control Studies; D001026:Coronary Artery Bypass / Q000379:methods; D003327:Coronary Disease / Q000601:surgery; D005260:Female; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011336:Probability; D017534:Radial Artery / Q000187:drug effects* / Q000637:transplantation*; D012016:Reference Values; D012680:Sensitivity and Specificity; D020858:Tissue and Organ Harvesting / Q000379:methods; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D014662:Vasoconstrictor Agents; D010643:Phenoxybenzamine; D010656:Phenylephrine; D009638:Norepinephrine