title: Increases in myocardial workload induced by rapid atrial pacing trigger alterations in global metabolism.
abstract: OBJECTIVE
  To determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.
  
  
  BACKGROUND
  There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis.
  
  
  METHODS
  Nineteen patients referred for cardiac catheterization were enrolled. Peripheral and selective coronary sinus (CS) blood sampling was performed at serial timepoints following the initiation of pacing, and metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS).
  
  
  RESULTS
  Pacing-stress resulted in a 225% increase in the median rate·pressure product from baseline. Increased myocardial work induced significant changes in the peripheral concentration of 43 of 125 metabolites assayed, including large changes in purine [adenosine (+99%, p = 0.006), ADP (+42%, p = 0.01), AMP (+79%, p = 0.004), GDP (+69%, p = 0.003), GMP (+58%, p = 0.01), IMP (+50%, p = 0.03), xanthine (+61%, p = 0.0006)], and several bile acid metabolites. The CS changes in metabolites qualitatively mirrored those in the peripheral blood in both timing and magnitude, suggesting the heart was not the major source of the metabolite release.
  
  
  CONCLUSIONS
  Isolated increases in myocardial work can induce changes in the plasma metabolome, but these changes do not appear to be directly cardiac in origin. A number of these dynamic metabolites have known signaling functions. Our study provides additional evidence to a growing body of literature on metabolic 'cross-talk' between the heart and other organs.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Aslan T
authors.initials: AT
authors.lastname: Turer
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: John F
authors.initials: JF
authors.lastname: O'Sullivan
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Sammy
authors.initials: S
authors.lastname: Elmariah
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Mega
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Tayo A
authors.initials: TA
authors.lastname: Addo
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.affiliation: Department of Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000787:Angina Pectoris / Q000097:blood* / Q000503:physiopathology; D001647:Bile Acids and Salts / Q000097:blood*; D002241:Carbohydrates / Q000097:blood; D006328:Cardiac Catheterization; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D015897:Comorbidity; D054326:Coronary Sinus; D005260:Female; D006321:Heart / Q000502:physiology; D006571:Heterocyclic Compounds / Q000097:blood; D006801:Humans; D008066:Lipolysis; D008297:Male; D013058:Mass Spectrometry; D024821:Metabolic Syndrome / Q000097:blood; D055442:Metabolome; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology*; D017202:Myocardial Ischemia / Q000097:blood / Q000503:physiopathology; D012907:Smoking / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D000596:Amino Acids; D001647:Bile Acids and Salts; D002241:Carbohydrates; D006571:Heterocyclic Compounds; D013963:Thyroid Hormones; D014365:Tryptophan Hydroxylase