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Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction

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Abstract

Nicorandil, a hybrid KATP channel opener and nicotinamide nitrate, reduces no-reflow phenomenon and improves cardiac function in patients with acute myocardial infarction (AMI). We repoted that nicorandil suppresses radical formation in patients with AMI undergoing primary percutaneous coronary intervention (PCI). In the present study, we tested the hypothesis that nicorandil treatment suppresses MMP activities and predicts ventricular remodeling in AMI. Sixty-two patients with AMI were randomized into nicorandil pretreatment (n = 31) and control (n = 31) groups after admission and underwent primary PCI. Nicorandil was administered as a bolus injection (4 mg) followed by constant infusion (8 mg/h) for 24 h just after admission. On days 1, 2, and 14 after the onset of AMI, the plasma levels of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by enzyme-linked immunosorbent assay and the activities by gelatin zymography. There were no differences in the baseline clinical characteristics between the two groups. On day 1, there were no differences in both MMP-2 and MMP-9 levels and their activities between the two groups. However, both MMP-2 and MMP-9 levels and their activities were significantly lower in nicorandil than in control group on day 2 (MMP-2 level, 1 014 ± 39 vs 1 174 ± 44 ng/ml; MMP-9 level, 17 ± 1 vs 23 ± 2 ng/ml; both P < 005) and on day l4 (MMP-2 level, 970 ± 38 vs 1 221 ± 44 ng/ml; MMP-9 level, 17 ± 1 vs 23 ± 1 ng/ml; both P < 0.05). Left ventricular end-diastolic volume index (LVEDVI) at acute phase was not different between the two groups. At 6 months after AMI, LVEDVI was significantly smaller in nicorandil than in the control group (83 ± 4 vs 96 ± 4 ml/m2, P < 0.05). The change in LVEDVI from acute phase to 6 months was positively correlated with MMP-2 and MMP-9 levels and activities. Nicorandil suppresses the increases in MMP levels and activities and prevents the development of ventricular remodeling in AMI.

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Authors and Affiliations

  1. Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan

    Takayuki Fujiwara, Toshiro Matsunaga, Kunihiko Kameda, Naoki Abe, Hirotsugu Ono, Takumi Higuma, Jin Yokoyama, Hiroyuki Hanada, Tomohiro Osanai & Ken Okumura

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  1. Takayuki Fujiwara
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  2. Toshiro Matsunaga
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  3. Kunihiko Kameda
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  4. Naoki Abe
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  5. Hirotsugu Ono
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  6. Takumi Higuma
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  7. Jin Yokoyama
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  8. Hiroyuki Hanada
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  9. Tomohiro Osanai
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  10. Ken Okumura
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Correspondence to Ken Okumura.

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Fujiwara, T., Matsunaga, T., Kameda, K. et al. Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction. Heart Vessels 22, 303–309 (2007). https://doi.org/10.1007/s00380-007-0975-z

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  • DOI: https://doi.org/10.1007/s00380-007-0975-z

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