Neural regulation of the proinflammatory cytokine response to acute myocardial infarction.
Within minutes of acute myocardial infarction (MI), proinflammatory cytokines increase in the brain, heart, and plasma. We hypothesized that cardiac afferent nerves stimulated by myocardial injury signal the brain to increase central cytokines. Urethane-anesthetized male Sprague-Dawley rats underwent ligation of the left anterior descending coronary artery (LAD) or sham LAD ligation after bilateral cervical vagotomy, sham vagotomy, or application of a 10% phenol solution to the epicardial surface of the myocardium at risk. MI caused a significant increase in tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in the plasma and heart, which was blunted by vagotomy. MI also caused a significant increase in hypothalamic TNF-alpha and IL-1beta, which was not affected by vagotomy. In contrast, epicardial phenol blocked MI-induced increases in hypothalamic TNF-alpha and IL-1beta without affecting increases in the plasma and heart. These findings demonstrate that the appearance of proinflammatory cytokines in the brain after MI is independent of blood-borne cytokines and suggest that cardiac sympathetic afferent nerves activated by myocardial ischemia signal the brain to increase cytokine production. In addition, an intact vagus nerve is required for the full expression of proinflammatory cytokines in the injured myocardium and in the circulation. We conclude that the sympathetic and parasympathetic innervation of the heart both contribute to the acute proinflammatory response to MI.
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Joseph
J
Francis
Zhi-Hua
ZH
Zhang
Robert M
RM
Weiss
Robert B
RB
Felder
D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003331:Coronary Vessels; D006321:Heart / Q000294:innervation*; D006439:Hemodynamics; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism*; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D009475:Neurons, Afferent; D051381:Rats; D017207:Rats, Sprague-Dawley; D013562:Sympathectomy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014628:Vagotomy
D018836:Inflammation Mediators; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha