Fujiwara Takayuki, Matsunaga Toshiro, Kameda Kunihiko, Abe Naoki, Ono Hirotsugu, Higuma Takumi, Yokoyama Jin, Hanada Hiroyuki, Osanai Tomohiro, Okumura Ken
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Heart Vessels. 2007 Sep;22(5):303-9. doi: 10.1007/s00380-007-0975-z. Epub 2007 Sep 20.
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 reported 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.
尼可地尔是一种兼具ATP敏感性钾通道开放剂和硝酸烟酰胺特性的药物，可减轻急性心肌梗死（AMI）患者的无复流现象并改善心功能。我们曾报道，尼可地尔可抑制接受直接经皮冠状动脉介入治疗（PCI）的AMI患者体内自由基的形成。在本研究中，我们验证了如下假说：尼可地尔治疗可抑制AMI患者基质金属蛋白酶（MMP）的活性，并预测心室重构情况。62例AMI患者入院后被随机分为尼可地尔预处理组（n = 31）和对照组（n = 31），并接受直接PCI治疗。入院后即刻给予尼可地尔静脉推注（4 mg），随后持续输注（8 mg/h）24小时。在AMI发病后的第1、2和14天，采用酶联免疫吸附测定法检测血浆基质金属蛋白酶（MMP）-2和MMP-9水平，并用明胶酶谱法检测其活性。两组患者的基线临床特征无差异。第1天时，两组患者的MMP-2和MMP-9水平及其活性均无差异。然而，在第2天（MMP-2水平：1 014±39 vs 1 174±44 ng/ml；MMP-9水平：17±1 vs 23±2 ng/ml；均P<0.05）和第14天（MMP-2水平：970±38 vs 1 221±44 ng/ml；MMP-9水平：17±1 vs 23±1 ng/ml；均P<0.05），尼可地尔组的MMP-2和MMP-9水平及其活性均显著低于对照组。急性期两组患者的左心室舒张末期容积指数（LVEDVI）无差异。AMI后6个月时，尼可地尔组的LVEDVI显著小于对照组（83±4 vs 96±4 ml/m2，P<0.05）。从急性期到6个月时LVEDVI的变化与MMP-2和MMP-9水平及活性呈正相关。尼可地尔可抑制AMI患者MMP水平及活性的升高，并预防心室重构的发生。
