eperfusion therapy, including percutaneous coronary intervention, reduces the mortality of patients with acute myocardial infarction (AMI), 1,2 but when AMI is complicated with cardiac rupture or ventricular septal perforation (VSP), the mortality rate is markedly increased. 3 Within a few days after the onset of AMI, proteases and reactive oxygen species are released from neutrophils infiltrating the infarcted cardiac tissue and these induce myocardial injury. 3, 4 In an experimental AMI

more »

... augmented activity of matrix metalloproteinase (MMP)-9, which is derived from neutrophils, was demonstrated in the infarcted area. 5-7 Furthermore, it was reported that knockout deletion of MMP-9 in mice prevented cardiac rupture complicating AMI. 7 These findings indicate that augmented MMP-9 activity derived from neutrophils may contribute to the development of cardiac rupture or VSP, but the pathophysiology in humans is unclear. By measuring the MMP activity and level of 8-isoprostagandin F2 (8-iso-PGF2 ) in the pericardial fluid (PF) in patients with coronary artery disease (CAD) undergoing coronary artery bypass graft surgery (CABG), we were able to recently report that cardiac MMP activity is related to ventricular remodeling and that oxidative stress Methods Patients' Profiles We enrolled 44 patients with CAD (34 men, 10 women; mean age 67±2 years (mean ± SEM)) who underwent CABG or closure of VSP: 28 had AP (AP group) and the other 16 had AMI (AMI group). In the AMI group, 5 had VSP (VSP group) and the remaining 11 did not (non-VSP AMI group). All AMI patients underwent cardiac surgery within 7 days of the onset of AMI. Diagnosis of AMI was made by typical symptoms, enzyme concentrations and Background In an animal model of acute myocardial infarction (AMI), deletion of matrix metalloproteinase (MMP)-9 results in suppression of the development of cardiac rupture. The present study sought to clarify how myocardial MMP-9 activity is related to the pathophysiologies of AMI and cardiac rupture in humans. Methods and Results Levels of interleukin-8 (IL-8), polymorphonuclear leukocyte (PMN) elastase, monocyte chemotactic protein-1 (MCP-1) and MMP activity were measured in the pericardial fluid obtained from 28 patients with angina pectoris (AP group) and 16 patients with AMI (AMI group) undergoing cardiac surgery. In the AMI group, 5 were complicated with ventricular septal perforation (VSP) and the remaining 11 were not (non-VSP). Levels of IL-8, PMN elastase, MMP-2 and MMP-9 activity were all higher in the AMI group than in the AP group. In the AMI group, all levels other than MMP-2 activity were further elevated in cases with VSP compared with those in the non-VSP group. There was no significant difference in MCP-1 among the groups Conclusions Markers of neutrophil activation in the infarcted cardiac tissue seem to be elevated in AMI. Highly elevated levels of MMP-9 activity, which may be derived from neutrophils, and PMN elastase may be related to the pathophysiology of VSP or cardiac rupture in AMI. (Circ J 2006; 70: 673 -678) R 674 KAMEDA K et al.