title: Beta-adrenergic regulation of the cerebral microcirculation after hypothermic cardiopulmonary bypass.
abstract: BACKGROUND
  The beta-adrenergic-cAMP pathway importantly regulates cerebral blood flow. Previous studies have found that normothermic cardiopulmonary bypass (CPB) is associated with reduced cerebral beta-adrenoceptor-mediated relaxation.
  
  
  RESULTS
  In order to examine the effects of hypothermic CPB on regulation of perfusion by the beta-adrenergic-cAMP pathway, pigs were placed on moderately (25 degrees C) or profoundly hypothermic (16 degrees C with 1 hour of circulatory arrest) or normothermic (37 degrees C) CPB for 2 hours. After normothermic perfusion for 15 minutes and separation from CPB, cerebral microvascular responses to the beta-adrenoceptor agonist isoproterenol (ISO), the adenylate cyclase activator forskolin, and the stable cAMP analogue 8-bromo-cAMP were examined in vitro in a pressurized, no-flow state. Baseline internal carotid artery blood flow was similar and unchanged after rewarming in the three experimental groups. However, ISO (100 micromol/L) elicited less relaxation after moderately hypothermic CPB (75+/-6%, P<.05 versus control, percent of U46619 induced precontraction) and profoundly hypothermic circulatory arrest (42+/-5%, P<.05) than in vessels from uninstrumented controls (91+/-2%) or after normothermic CPB (84+/-4%). The relaxation to forskolin was reduced after profoundly hypothermic circulatory arrest (83+/-3%, P<.05), but was similar in the other groups (92+/-2% control). Surprisingly, relaxation induced by 8-bromo-cAMP was markedly reduced after normothermic CPB, and this change was directly related to temperature during CPB. The intraluminal exposure of vessels to zymosan-induced complement activated serum had no effect on relaxation to ISO, while 2 hours of exposure of vessels to ISO caused a dose-dependent reduction in subsequent relaxation to ISO, but not to forskolin.
  
  
  CONCLUSIONS
  Moderately hypothermic CPB or PHCA desensitizes alpha-adrenoceptors more than normothermic CPB. This is likely due in part to the exposure of vessels to endogenous catecholamines during CPB. Thus, whereas baseline cerebral blood flow is similar after normothermic and hypothermic CPB, beta-adrenergic responses are markedly abnormal.
authors.affiliation: Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass 02215, USA.
authors.forename: F W
authors.initials: FW
authors.lastname: Sellke
authors.forename: M
authors.initials: M
authors.lastname: Tofukuji
authors.forename: A
authors.initials: A
authors.lastname: Stamler
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: S Y
authors.initials: SY
authors.lastname: Wang
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002315:Cardiopulmonary Bypass; D002560:Cerebrovascular Circulation; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D007036:Hypothermia, Induced; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008833:Microcirculation; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013552:Swine
chemical_list: D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol