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Vagal Stimulation, Through its Nicotinic Action, Limits Infarct Size and the Inflammatory Response to Myocardial Ischemia and Reperfusion

Calvillo, Laura PhD*; Vanoli, Emilio MD†,‡; Andreoli, Elisa PhD; Besana, Alessandra PhD*; Omodeo, Elisabetta PhD§; Gnecchi, Massimiliano MD, PhD†,¶; Zerbi, Pietro MD§; Vago, Gianluca MD§; Busca, Giuseppe; Schwartz, Peter J. MD†,¶,**,††

Journal of Cardiovascular Pharmacology: November 2011 - Volume 58 - Issue 5 - p 500–507
doi: 10.1097/FJC.0b013e31822b7204
Original Article
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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.

*Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy

Section of Cardiology, Department of Lung, Blood and Heart, University of Pavia, Pavia, Italy

Department of Cardiology, Policlinico di Monza, Monza, Italy

§Pathology Unit, Institute of Biomedical Sciences, L. Sacco Hospital, The University of Milan, Italy

Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy

Department of Cardiovascular Medicine, The University of Milan, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy

**Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, South Africa

††Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Reprints: Peter J. Schwartz, MD, Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Viale Golgi 19, 27100 Pavia, Italy (e-mail: peter.schwartz@unipv.it).

The authors report no conflict of interest.

Received May 12, 2011

Accepted June 28, 2011

© 2011 Lippincott Williams & Wilkins, Inc.