Myocardial ischemia-reperfusion injury associated with cardiac surgery is an acute inflammatory process in which activated leukocytes and endothelial cells play a critical role. Recent data indicate that the release of cytokines is crucial in inducing leukocytes and endothelial cells activation during cardiopulmonary bypass (CPB). Some inflammatory cytokines can be produced locally from the heart, particularly interleukin (IL)-8, which may further enhance leukocyte activation and accumulation in the injured myocardium. In fact, postoperative levels of cardiac troponin-I, a highly specific marker of myocardial injury, correlated strongly with IL-8 values in patients undergoing coronary artery bypass grafting (CABG). Off-pump CABG is associated with less IL-8 production compared with conventional procedure, which may in turn reduce the degree of myocardial injury. On the other hand, reduced release of IL-8 and cardiac troponin-I has also been discovered following the use of heparin-coated CPB circuits. In addition, the balance between pro- and anti-inflammatory mediators may be even more crucial in determining the extent of injury. Hence, avoiding the use of CPB or improving the biocompatibility of CPB may lead to better myocardial preservation. Research along these lines is expected to help in the development of ideal therapeutic strategies to minimize the inflammatory response and subsequent myocardial injury associated with cardiac surgery.

Plasma levels of neuropeptide Y (NPY) are elevated in patients with acute myocardial infarction (AMI), but its role in AMI remains unclear, which was examined here in NPY wild-type/knockout (WT/KO) mice treated with/without exogenous NPY and its Y1 receptor antagonist (Y1Ra) BIBP 3226. We found that AMI mice lacking NPY developed more severe AMI than WT mice with worse cardiac dysfunction, progressive cardiac inflammation and fibrosis, and excessive apoptosis but impairing angiogenesis. All of these changes were reversed when the NPY KO mice were treated with exogenous NPY in a dose-dependent manner. Interestingly, treatment with NPY also dose dependently attenuated AMI in WT mice, which was blocked by BIBP 3226. Phenotypically, cardiac NPY was de novo expressed by infiltrating macrophages during the repairing or fibrosing process in heart-failure patients and AMI mice. Mechanistically, NPY was induced by transforming growth factor (TGF)-β1 in bone marrow-derived macrophages and signaled through its Y1R to exert its pathophysiological activities by inhibiting p38/nuclear factor κB (NF-κB)-mediated M1 macrophage activation while promoting the reparative M2 phenotype in vivo and in vitro. In conclusion, NPY can attenuate AMI in mice. Inhibition of cardiac inflammation and fibrosis while enhancing angiogenesis but reducing apoptosis may be the underlying mechanisms through which NPY attenuates cardiac remodeling and deterioration of function following AMI.