Increases in myocardial workload induced by rapid atrial pacing trigger alterations in global metabolism

• Published in: PloS one Vol. 9; no. 6; p. e99058
• Main Authors: Turer, Aslan T, Lewis, Gregory D, O'Sullivan, John F, Elmariah, Sammy, Mega, Jessica L, Addo, Tayo A, Sabatine, Marc S, de Lemos, James A, Gerszten, Robert E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.06.2014; Public Library of Science (PLoS)
• Subjects: Adenosine; Adenosine diphosphate; Alterations; Amino Acids - metabolism; AMP; Angina pectoris; Angina Pectoris - blood; Angina Pectoris - physiopathology; Angioplasty; Bile Acids and Salts - blood; Biology and Life Sciences; Blood; Carbohydrates - blood; Cardiac Catheterization; Cardiac Pacing, Artificial - adverse effects; Cardiac patients; Cardiology; Cardiovascular disease; Catheterization; Catheters; Chromatography; Comorbidity; Coronary Sinus; Coronary vessels; Energy balance; Female; Gross domestic product; Heart; Heart - physiology; Heart diseases; Heart rate; Heterocyclic Compounds - blood; Homeostasis; Hospitals; Humans; Inosine monophosphate; Internal medicine; Intubation; Ischemia; Lipolysis; Liquid chromatography; Male; Mass Spectrometry; Mass spectroscopy; Medical imaging; Medicine; Medicine and Health Sciences; Metabolic Syndrome - blood; Metabolism; Metabolites; Metabolome; Middle Aged; Myocardial Contraction - physiology; Myocardial Ischemia - blood; Myocardial Ischemia - physiopathology; Organs; Patients; Peripheral blood; Physiological aspects; Scientific imaging; Signaling; Sinus; Smoking - blood; Thyroid Hormones - blood; Tryptophan Hydroxylase - metabolism; Womens health; Xanthine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0099058

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. There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis. 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). 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. 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.