title: Vagal stimulation, through its nicotinic action, limits infarct size and the inflammatory response to myocardial ischemia and reperfusion.
abstract: Vagal activity has protective effects in ischemic heart disease. We tested whether vagal stimulation (VS) could modulate the inflammatory reaction, a major determinant of cardiac injury after ischemia/reperfusion. Four groups of male rats underwent myocardial ischemia (30 minutes) and reperfusion (24 hours). One group underwent VS (40 minutes), 1 VS plus atrial pacing (VS + Pacing), and 1 VS plus nicotinic inhibition by mecamylamine (VS + MEC). After 24 hours, the area at risk, infarct size, inflammation parameters, and apoptosis were quantified. Infarct size was reduced in all VS-treated rats (controls, 53 ± 18%; VS, 6.5 ± 3%; VS + Pacing, 23 ± 6%; VS + MEC, 33 ± 9%; P < 0.005 vs. controls). The infarct size in the VS + MEC group was larger than that in VS-treated animals, despite similar heart rate, suggesting partial loss of protection. The number of macrophages, neutrophils, and apoptotic cells in the area at risk and the plasma cytokines levels were significantly reduced in all VS-treated animals. In conclusion, VS decreases infarct size and inflammatory markers during ischemia/reperfusion independent of the heart rate. The anti-inflammatory and antiapoptotic properties of the nicotinic pathway are the primary underlying mechanism. The vagally mediated modulation of inflammatory responses may prove valuable in the clinical management of acute coronary syndromes and of heart failure.
authors.affiliation: Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Calvillo
authors.forename: Emilio
authors.initials: E
authors.lastname: Vanoli
authors.forename: Elisa
authors.initials: E
authors.lastname: Andreoli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Besana
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Omodeo
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gnecchi
authors.forename: Pietro
authors.initials: P
authors.lastname: Zerbi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Vago
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Busca
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002304:Cardiac Pacing, Artificial; D018932:Chemokine CCL2 / Q000097:blood; D054365:Chemokine CXCL5 / Q000097:blood; D006339:Heart Rate / Q000502:physiology; D007249:Inflammation / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009203:Myocardial Infarction / Q000473:pathology* / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D055536:Vagus Nerve Stimulation; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054365:Chemokine CXCL5; C579165:Chrna7 protein, rat; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D008464:Mecamylamine