title: Neuronally induced augmentation of cardiac output.
abstract: OBJECTIVE
  To determine whether cardiac output can be augmented by preferentially activating cardiac adrenergic efferent neurons.
  
  
  METHODS
  Elicited cardiac output responses were compared when cardiac myocytes were directly stimulated by a beta1-adrenoceptor agonist versus when they were indirectly influenced by beta2- adrenergic-sensitive cardiac efferent neurons.
  
  
  METHODS
  The beta1-adrenoceptor agonist dobutamine or the selective beta2-adrenoceptor agonist terbutaline was continuously infused individually into the systemic circulation of 15 anesthetized pigs for 20 mins in 5 and 15 microgram/kg/min doses. Heart rate, left atrial chamber pressure, regional left ventricular intramyocardial systolic pressure, left ventricular chamber pressure and aortic pressure were monitored. Cardiac output was determined via the thermodilution technique before and at 10 min intervals during drug infusions. Ventricular tissues were removed thereafter and immediately frozen in liquid nitrogen for subsequent cardiac myocyte cell surface beta-adrenoceptor analysis.
  
  
  RESULTS
  Both doses of terbutaline increased heart rate (approximately +18%) and cardiac output (approximately +20%). Heart rate (+12%) and cardiac output (+16%) increased when the high dose of dobutamine was tested. Left ventricular intramyocardial systolic pressure was increased by dobutamine (+15%) but not by terbutaline. Porcine ventricular cardiac myocytes primarily possess cell surface beta1-, rather than beta2-, adrenoceptors, making it unlikely that cardiac myocytes were directly affected by the doses of terbutaline tested.
  
  
  CONCLUSIONS
  Beta2-adrenoceptor agonists enhance cardiac output primarily as a result of neuronally induced increases in heart rate in the porcine model. Adrenergic efferent neuronal enhancement of heart rate may be an effective way to increase cardiac output independently of directly augmented ventricular dynamics. Further study is required to determine whether the diseased myocardium can be supported by such neurocardiological means.
authors.affiliation: Dalhousie University, Halifax, Canada.
authors.forename: R S
authors.initials: RS
authors.lastname: Stevenson
authors.forename: G W
authors.initials: GW
authors.lastname: Thompson
authors.forename: M
authors.initials: M
authors.lastname: Wilkinson
authors.forename: D A
authors.initials: DA
authors.lastname: Murphy
authors.forename: J A
authors.initials: JA
authors.lastname: Armour
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D009474:Neurons; D013552:Swine; D013726:Terbutaline / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D002316:Cardiotonic Agents; D004280:Dobutamine; D013726:Terbutaline