Increased Pericardial Fluid Level of Matrix Metalloproteinase-9 Activity in Patients With Acute Myocardial Infarction Possible Role in the Development of Cardiac Rupture

Abstract

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 model, 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 Circulation Journal Vol.70, June 2006might play an important role in the regulation of MMP activity. 8 PF is considered to reflect not only the ultrafiltrate of the plasma, but also the transudate from the cardiac interstitium. 9 However, PF obtained from patients with freewall-type cardiac rupture is not suitable for investigating the cardiac interstitium because of considerable contamination with blood. Non-hemorrhagic PF can be obtained from patients with VSP because the pathogenesis is generally considered as almost identical to free wall cardiac rupture. 3 To clarify the role of neutrophil and MMP activity in the pathophysiology of AMI and cardiac rupture, we measured the concentrations of interleukin-8 (IL-8), a chemoattractant of neutrophils, 10 monocyte chemotactic protein-1 (MCP-1), a chemoattractant of monocytes, 11 polymorphonuclear leukocyte (PMN) elastase, a marker of neutrophil activation, 12 and MMP activity in PF obtained from 44 patients with angina pectoris (AP) or AMI with or without VSP, who underwent CABG or closure of the VSP. Methods Patients' ProfilesWe 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 a...

White Blood Cell Count and Risk of All-Cause and Cardiovascular Mortality in Nationwide Sample of Japanese

“…Neversmokers with WBC counts of 9,000-10,000 cells/mm 3 had over a 3-fold elevated risk for CVD death compared with those with WBC counts of 4,000-4,900 cells/mm 3 (RR = 3.20, 1.25-8.24). When 6 categories were combined into Tables 1,2. 2 categories, never-smokers with WBC counts of 8,000-10,000 cells/mm 3 had a 2-fold high risk of CVD (RR = 2.05, 1.12-3.76) compared with those with WBC counts of 4,000-7,900 cells/mm 3 . Table 5 shows the effect of modification of BMI on the associations between WBC count and all-cause and CVD mortality.…”

“…Since similar RRs for lowest to 4 th and 5 th to highest were observed, these categories were analyzed in combination. Women with WBC counts of 8,000-10,000 cells/mm 3 had over a 2-fold elevated risk of CVD (RR =2.18, 1.23-3.88) compared with those with WBC counts of 4,000-7,900 cells/mm 3 . Additionally, in the context of public health practice, women with WBC counts of 8,000-10,000 cells/mm 3 had a 1.5-fold borderline significantly higher risk for all-cause mortality (RR =1.50, 0.95-2.37) and a 2.2-fold significantly higher risk for CVD mortality (RR =2.22, 1.06-4.62) compared to those with WBC counts of 4,000-4,900 cells/mm 3 .…”

“…11 The WHI-OS reported that the RR of CHD, stroke, and CVD were 2.36 (95% CI: 1.51-3.68), 1.46 (95% CI: 1.17-1.81) and 1.47 (95% CI: 1.26-1.72) among women in the upper quartile of WBC counts (6,,000 cells/mm 3 ) compared with those in the lowest quartile (2,500-4,700 cells/mm 3 ) although several causes that lead to elevated or decreased WBC counts beyond normal limits need to be considered in the interpretation of the results. WHI-OS also showed that the upper quartile was a threshold for elevated risk and was approximated by a WBC count of greater than 6,700 cells/mm 3 (RR of CVD mortality: 1.00 (lowest quartile: referent), 1.01 (second quartile), 1.12 (third quartile), 1.47 (upper quartile)). Such a threshold effect was also observed in the present study (RR of CVD mortality: 1.00 (WBC of 4,000-4,900 cells/mm 3 : referent), 1.02 (WBC of 5,000-5,900 cells/mm 3 ), 1.12 (WBC of 6,000-6,900 cells/mm 3 : referent), 0.88 (WBC of 7,000-7,900 cells/mm 3 ), 2.04 (WBC of 8,000-8,900 cells/mm 3 ), 2.66 (WBC of 9,000-10,000 cells/mm 3 ); WBC of 8,000-10,000 vs WBC of 4,000-7,900: RR =2.18, 1.23-3.88).…”

“…These tubes were stored at room temperature and collected during the morning of the day after blood collection by a commercial hematological laboratory (SRL, Tokyo, Japan). The WBC counts were measured with an automatic hematology analyzer (E-3000, Toa Medical Electronics, Kobe, Japan) and expressed as 100 cells/mm 3 . Hemoglobin (Hb) A1c was measured using the latex agglutination method.…”

“…The survey response rate was 76.5%. Of the 8,384 participants, we excluded subjects with any of the following criteria: past history of stroke (n=159), past history of CHD (n=230), missing information on lifestyle factors or body size (n=113), no available data to evaluate a vital criteria during the follow-up period (n=182), missing information on WBC count at baseline or metabolic parameters (n=550), subjects with WBC counts of less than 4,000 cells/mm 3 indicating clinical leucopenia (n=217) and subjects with WBC counts of more than 10,000 cells/mm 3 indicating clinically relevant inflammatory conditions (n=306). We limited WBC count from 4,000 to 10,000 cells/mm 3 to minimize the potential influences of several factors related to elevated or decreased WBC counts beyond normal limits.…”