title: alpha 1-Adrenergic responsiveness during coronary artery bypass surgery: effect of preoperative ejection fraction.
abstract: Elevated catecholamines and beta-adrenergic receptor hyporesponsiveness (or desensitization) have been demonstrated in failing human myocardium, but the role of the alpha-adrenergic receptor remains unclear. The authors tested the hypothesis that alpha 1-adrenergic responsiveness decreases in patients with impaired ventricular function undergoing coronary artery revascularization. Impaired ventricular function was defined prospectively by left ventricular ejection fraction less than or equal to 40% (group I, n = 12), and normal ventricular function by ejection fraction greater than 40% (group II, n = 22). Phenylephrine (Phe) pressor dose-response curves were established prior to anesthesia, during fentanyl anesthesia, and during fentanyl anesthesia plus hypothermic cardiopulmonary bypass at the time of aortic cross-clamp (anes + CPB/AXC). Polynomial regression of the Phe dose response curve estimated the Phe dose required to increase mean arterial blood pressure 20%, designated PD20. Although pre-anesthesia PD20 and anes + CPB/AXC PD20 values were not affected by ejection fraction, significant differences in PD20 (P less than 0.05) between groups occurred during fentanyl anesthesia (group I = 2.28 +/- 1.60 micrograms.kg-1, group II 1.57 +/- 0.98 micrograms.kg-1; mean +/- SD). Anes + CPB/AXC was associated with a significant reduction in PD20 in both groups compared with pre-anesthesia (P less than 0.01). Our results suggest impairment of alpha 1-adrenergic responsiveness occurs during fentanyl anesthesia in patients with ejection fractions less than or equal to 40% (evidenced by greater PD20 values). Although this impairment may be due to altered Phe pharmacokinetics, these results also support the possible existance of alpha 1-adrenergic receptor desensitization in this group. Reduction in PD20 during anes + CPB/AXC in all patients points to more powerful effects than fentanyl anesthesia alone; such influencing effects may include hemodilution, hypothermia, elevated plasma catecholamines, exclusion of the pulmonary circulation, or altered Phe pharmacokinetics.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: D A
authors.initials: DA
authors.lastname: Schwinn
authors.forename: R W
authors.initials: RW
authors.lastname: McIntyre
authors.forename: E D
authors.initials: ED
authors.lastname: Hawkins
authors.forename: R A
authors.initials: RA
authors.lastname: Kates
authors.forename: J G
authors.initials: JG
authors.lastname: Reves
mesh_terms: D000771:Anesthesia, Intravenous; D001794:Blood Pressure / Q000187:drug effects; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005283:Fentanyl / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013318:Stroke Volume
chemical_list: D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D005283:Fentanyl