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

Aslan T Turer,Gregory D Lewis,John F O'Sullivan,Robert E Gerszten,Jessica L Mega,Tayo A Addo,Marc S Sabatine,Sammy Elmariah,James A De Lemos

doi:10.1371/journal.pone.0099058

Abstract

ObjectiveTo determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.BackgroundThere is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis.MethodsNineteen 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).ResultsPacing-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.ConclusionsIsolated 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.

Highlights

The coronary sinus (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
Our study provides additional evidence to a growing body of literature on metabolic ‘cross-talk’ between the heart and other organs

Summary

Introduction

There has been a long history of investigation into myocardial substrate selection and energetics during periods of increased cardiac work and in the context of myocardial ischemia. Global metabolite profiling has been performed to gain insights into additional metabolic pathways active during periods of myocardial stress, e.g. ischemia [1,2,3], infarction [4], and exercise [5]. It is unknown whether changes in peripheral metabolism can occur directly as a consequence of increases in myocardial work This is an important question, as it is becoming increasingly recognized that the heart is able to influence metabolic events in non-cardiac tissues by endocrine effects. Additional humoral pathways linking both skeletal muscle [7] and the heart [8] to energy homeostasis have recently been described Taken together, these lines of evidence suggest that increases in cardiac work alone may be able to induce metabolic effects on peripheral tissues in humans. There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis

Methods

Results

Conclusion