Extracellular matrix disturbances in acute myocardial infarction: relation between disease severity and matrix metalloproteinase-1, and effects of magnesium pretreatment on reperfusion injury.
OBJECTIVE
The purpose of this paper is to clarify the relationship between cytokines, matrix metalloproteinase-1 (MMP-1) and severity of acute myocardial infarction (AMI). Additionally, to investigate whether magnesium (Mg) sulfate pretreatment inhibits myocardial damage in coronary reperfusion therapy for patients with AMI.


METHODS
At first, 34 patients with AMI were enrolled. Then, the patients were classified into 2 groups with or without congestive heart failure (CHF) (C group and NC group, respectively). Interleukin 6 (IL-6), MMP-1 and the hemodynamic parameters were measured. Second, 36 AMI patients treated with coronary reperfusion therapy were enrolled. Patients were divided into 2 groups (18 patients each) as the non-pretreated group (Control group) and the group pretreated with intravenous Mg sulfate (0.27 mmol/kg) (Mg group). IL-6, MMP-1 and the indexes of reperfusion injury were evaluated.


RESULTS
There were positive correlations between peak MMP-1 level, and peak creatine kinase value and pulmonary capillary wedge pressure and peak IL-6 level (r = 0.43, r = 0.70, and r = 0.60, respectively) in all patients. There were negative correlations between peak MMP-1 level and left ventricular ejection fraction and cardiac index (r = - 0.52 and r = - 0.55, respectively). The peak blood IL-6 and MMP-1 level increased in AMI, particularly in patients with CHF (C group vs NC group; 130 vs 51 pg/mL and 37 vs 18 ng/mL, both p < 0.01). Additionally, peak IL-6 and peak MMP-1 in the Mg group were lower than those of the control group (39 vs 92 pg/mL and 16 vs 20 ng/mL, p < 0.05 and p = 0.09, respectively). The incidence of reperfusion injury including reperfusion arrhythmia and transient exacerbation of ST elevation in the Mg group was lower than that of control group (17 vs 78% and 2.5 vs 4.7 mm, p < 0.01 and p = 0.08, respectively).


CONCLUSIONS
These results may suggest that the severity of AMI is reflected by the blood IL-6 and MMP-1 levels and that pretreatment with Mg administration protects the myocardium of patients with AMI from reperfusion injury induced by IL-6 and MMP-1.
Ueshima
Kenji
K
Second Department of Internal Medicine, Iwate Medical University, Morioka, Japan. k-ueshima@imu.ncvc.go.jp
Shibata
Masashi
M
Suzuki
Tomomi
T
Endo
Shigeatsu
S
Hiramori
Katsuhiko
K
D000368:Aged; D001145:Arrhythmias, Cardiac; D002196:Capillaries / Q000473:pathology; D003402:Creatine Kinase / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D008278:Magnesium Sulfate / Q000494:pharmacology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology*; D011312:Pressure; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors
D015850:Interleukin-6; D008278:Magnesium Sulfate; D003402:Creatine Kinase; D020781:Matrix Metalloproteinase 1; D008274:Magnesium