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Effect of Magnesium Sulfate Pretreatment and Significance of Matrix Metalloproteinase-1 and Interleukin-6 Levels in Coronary Reperfusion Therapy for Patients with Acute Myocardial Infarction

Kenji Ueshima, MD

Masako Harada, MD

Moyoyuki Nakamura, MD

Katsuhiko Hiramori, MD

Shigeatsu Endo, MD

Norio Sato, MD

Harumi Mukaida, MD

Tomomi Suzuki, MD

Tomoyuki Suzuki, MD

Katsuya Inada, PhD

Masashi Shibata, MD

Second Department of Internal Medicine 19-1 Uchimaru Morioka Iwate 020-8505 Japan

Magnesium (Mg) inhibits the influx of calcium in vascular smooth muscle cells. The purposes of this study were to test the hypothesis that an intravenous administration of magnesium might effect the complement response and to determine the effects of a magnesium pretreatment of patients with acute myocardial infarction (AMI) on the incidence of reperfusion injuries. Thirty-eight AMI patients were treated with coronary reperfusion therapy within 6 hours of onset. They were randomly divided into two groups: group pretreated with intravenous magnesium sulfate (0.27 mmol/kg) (magnesium group, n=19), and nonpretreated controls (placebo group). The reperfu sion injuries observed within 1 hour after the coronary reperfusion included arrhyth mias, aggravated chest pain, and ST segment elevation in 12-lead electrocardiograms. Coronary recanalization was performed in 36 patients. The incidence of reperfusion arrhythmia was significantly lower in the magnesium group than in the placebo group (17% vs 78%, p<0.001). At the postreperfusion stage, there was a tendency for the degree of ST segment reelevation in the magnesium group lower than in the placebo group (2.5 ±2.3 mm vs 4.7 ±3.8 mm, p=0.07). No marked difference was observed in the incidence of chest pain aggravation between the two groups (67% vs 73%, ns). The peak serum levels of interleukin-6 (IL-6) were significantly lower in the magnesium group than those in the placebo group (38.9 ±25.0 vs 92.3 ±76.5 pg/mL, p=0.016). The peak serum levels of matrix metalloproteinase-1 (MMP-1) were lower than those in the placebo group (16.2 ±4.8 vs 19.7 ±9.0 ng/mL, p=0.09), but the difference was not significant. A positive correlation was observed between the peak MMP-1 values and the peak IL-6 values (r=0.57, p=0.001) in all patients. Increased serum ionized Mg²⁺ may inhibit arrhythmic recurrence and the production of IL-6 and MMP-1 after reperfusion and prevent the increase of myocardial lesions caused by calcium overload on myocytes. The increased IL-6 production may induce MMP-1, leading to tissue organ injury. Pretreatment with magnesium sulfate may protect the myocardium of AMI patients from reperfusion injuries.

Angiology, Vol. 50, No. 7, 573-582 (1999)
DOI: 10.1177/000331979905000707


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