title: Effect of severe acidosis on vasoactive effects of epinephrine and norepinephrine in human distal mammary artery.
abstract: OBJECTIVE
  Acidosis is a very common pathologic process in perioperative management. However, how to correct severe acidosis to improve the efficacy of vasoconstrictors in hemodynamically unstable patients is still debated. The present study investigated whether severe extracellular acidosis influences the vasoactive properties of vasoconstrictors on human isolated arteries.
  
  
  METHODS
  Segments of intact distal internal mammary arteries were removed from 41 patients undergoing artery bypass grafting. The arterial rings were washed in Krebs-Henseleit solution and suspended in an organ bath. The rings were set at a pretension equivalent of 100 mm Hg, and the relaxation response to 10 μM acetylcholine was verified. Concentration-response curves for epinephrine, norepinephrine, methoxamine (α1A/D-adrenoceptor agonist), phenylephrine (equipotent agonist of α1A/B-adrenoceptors), and clonidine (α2-adrenoceptor agonist) were achieved under control conditions (pH 7.40) and under acidic conditions by substitution of the Krebs-Henseleit solution with a modified solution.
  
  
  RESULTS
  Decreasing the pH from 7.40 to 7.20, 7.0, or 6.80 did not significantly alter the potency and efficacy of epinephrine and norepinephrine, although the standardized effect size was sometimes large. Severe acidosis (pH 6.80) did not significantly change the potency and efficacy of phenylephrine and clonidine, although it increased the efficacy and potency of methoxamine (P < .001 and P = .04 vs paired control conditions, respectively).
  
  
  CONCLUSIONS
  Extracellular acidosis did not impair the vasoactive properties of epinephrine and norepinephrine in human medium-size arteries until pH 6.80. The results of the present study also suggest that acidosis might potentiate arterial responsiveness to vasoconstrictors, mostly by way of the α1D-adrenoceptor.
authors: Research Unit UPRES EA220, Versailles Saint-Quentin-en-Yvelines University, Hôpital Foch, Suresnes, France; Medical Intensive Care Unit, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Charles
authors: C
authors: Vidal
authors: Research Unit UPRES EA220, Versailles Saint-Quentin-en-Yvelines University, Hôpital Foch, Suresnes, France.
authors: Stanislas
authors: S
authors: Grassin-Delyle
authors: Research Unit UPRES EA220, Versailles Saint-Quentin-en-Yvelines University, Hôpital Foch, Suresnes, France.
authors: Philippe
authors: P
authors: Devillier
authors: Research Unit UPRES EA220, Versailles Saint-Quentin-en-Yvelines University, Hôpital Foch, Suresnes, France.
authors: Emmanuel
authors: E
authors: Naline
authors: Department of Cardiovascular Surgery, Institut Mutualiste Montsouris, Paris, France.
authors: Emmanuel
authors: E
authors: Lansac
authors: Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Philippe
authors: P
authors: Ménasché
authors: Research Unit UPRES EA220, Versailles Saint-Quentin-en-Yvelines University, Hôpital Foch, Suresnes, France; Medical Intensive Care Unit, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address: christophe.faisy@egp.aphp.fr.
authors: Christophe
authors: C
authors: Faisy
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000368:Aged; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008729:Methoxamine / Q000494:pharmacology; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine