Acute vagal stimulation attenuates cardiac metabolic response to beta-adrenergic stress

作者:Vimercati Claudio; Qanud Khaled; Ilsar Itamar; Mitacchione Gianfranco; Sarnari Roberto; Mania Daniella; Faulk Ryan; Stanley William C; Sabbah Hani N; Recchia Fabio A*
来源:The Journal of Physiology, 2012, 590(23): 6065-6074.
DOI:10.1113/jphysiol.2012.241943

摘要

The effects of vagal stimulation (VS) on cardiac energy substrate metabolism are unknown. We tested the hypothesis that acute VS alters the balance between free fatty acid (FFA) and carbohydrate oxidation and opposes the metabolic effects of beta-adrenergic stimulation. A clinical-type selective stimulator of the vagal efferent fibres was connected to the intact right vagus in chronically instrumented dogs. VS was set to reduce heart rate by 30 beats min-1, and the confounding effects of bradycardia were then eliminated by pacing the heart at 165 beats min-1. [3H]Oleate and [14C]glucose were infused to measure FFA and glucose oxidation. The heart was subjected to beta-adrenergic stress by infusing dobutamine at 5, 10 and 15 mu g kg-1 min-1 before and during VS. VS did not significantly affect baseline cardiac performance, haemodynamics or myocardial metabolism. However, at peak dobutamine stress, VS attenuated the increase in left ventricular pressurediameter area from 235.9 +/- 72.8 to 167.3 +/- 55.8%, and in cardiac oxygen consumption from 173.9 +/- 23.3 to 127.89 +/- 6.2% (both P %26lt; 0.05), and thus mechanical efficiency was not enhanced. The increase in glucose oxidation fell from 289.3 +/- 55.5 to 131.1 +/- 20.9%(P %26lt; 0.05), while FFA oxidation was not increased by beta- adrenergic stress and fell below baseline during VS only at the lowest dose of dobutamine. The functional and in part the metabolic changes were reversed by 0.1 mg kg-1 atropine i.v. Our data show that acute right VS does not affect baseline cardiac metabolism, but attenuates myocardial oxygen consumption and glucose oxidation in response to adrenergic stress, thus functioning as a cardio-selective antagonist to beta-adrenergic activation.

  • 出版日期2012-12