title: A study of the physiological consequences of sympathetic denervation of the heart caused by the arterial switch procedure.
abstract: BACKGROUND
  The arterial switch operation is the corrective operation for transposition of the great arteries, defined as the combination of concordant atrioventricular and discordant ventriculo-arterial connections, but there have been concerns about silent subendocardial ischaemia on exercise and coronary artery growth. The arterial switch divides the majority of the sympathetic nerves entering the heart; we have studied the effects of coronary flow and sensitivity to catecholamine stimulation in an animal model.
  
  
  METHODS
  A total of 10 piglets were operated on cardiopulmonary bypass with section and resuturing of aortic trunk, pulmonary artery and both coronary arteries, with 13 sham-operated controls. After 5-7 weeks of recovery, seven simulated switch survivors and 13 controls were studied.
  
  
  RESULTS
  Basal heart rate was significantly higher in switch piglets: in vivo mean (standard deviation) 112 (12) versus sham 100 (10) beats per minute, (p = 0.042); in vitro (Langendorff preparation): 89 (9) versus sham 73 (8) beats per minute (p = 0.0056). In vivo maximal heart rate in response to epinephrine was increased in switch piglets, 209 (13) versus 190 (17) beats per minute (p = 0.044). In vitro dose-response curves to norepinephrine were shifted leftward and upwards (p = 0.0014), with an 80% increase in heart rate induced by 0.095 (0.053) norepinephrine micromole per litre perfusate in switch hearts versus 0.180 (0.035) norepinephrine micromole per litre (p = 0.023). Increase in coronary flow on norepinephrine stimulation and maximal coronary flow were significantly reduced in switch hearts: 0.3 (0.2) versus 0.8 (0.4) millilitre per gram heart weight (p = 0.045) and 2.5 (0.4) versus 3.1 (0.4) millilitre per gram heart (p = 0.030), respectively.
  
  
  CONCLUSIONS
  A combination of increased intrinsic heart rate, increased sensitivity to chronotropic actions of norepinephrine, and a decreased maximal coronary flow creates potential for a mismatch between perfusion and energy demands.
authors.affiliation: Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, Queen Silvia Children's Hospital, Gothenburg University, Gothenburg, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Falkenberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Hallhagen
authors.forename: Krister
authors.initials: K
authors.lastname: Nilsson
authors.forename: Boris
authors.initials: B
authors.lastname: Nilsson
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Ostman-Smith
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000294:innervation* / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000008:administration & dosage; D012039:Regional Blood Flow; D013552:Swine; D013566:Sympathomimetics / Q000008:administration & dosage; D014188:Transposition of Great Vessels / Q000503:physiopathology* / Q000601:surgery*
chemical_list: D013566:Sympathomimetics; D009638:Norepinephrine