Nakamura Ryosai, Kato Johji, Kitamura Kazuo, Onitsuka Hisamitsu, Imamura Takuroh, Marutsuka Kousuke, Asada Yujiro, Kangawa Kenji, Eto Tanenao
First Department of Internal Medicine, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki, Japan.
Cardiovasc Res. 2002 Dec;56(3):373-80. doi: 10.1016/s0008-6363(02)00594-1.
We previously reported that plasma adrenomedullin (AM) levels increase in patients with acute myocardial infarction (MI) and AM inhibits growth of rat cardiac myocytes and fibroblasts. The aim of this study was to examine the effects of long-term administration of AM on left ventricular (LV) remodeling, hemodynamic and hormonal parameters in a rat model of MI.
Rats with MI induced by left coronary ligation were intravenously infused with 1.0 microg/h of recombinant human AM or saline by osmotic mini-pump. After infusion for 4 weeks, hemodynamic and hormonal studies were performed, and the myocyte size and collagen volume in non-infarct LV area were quantified morphometrically.
When compared with the MI rats infused with saline, continuous infusion of AM reduced the heart weight/body weight (4.4+/-0.2 vs. 3.6+/-0.1 g/kg, P<0.01), myocyte size (922+/-23 vs. 868+/-10 microm(2), P<0.05) and collagen volume fraction of non-infarct LV area (7.6+/-0.8 vs. 4.8+/-0.5%, P<0.05), without affecting the infarct size. The AM infusion had no significant effect on the arterial pressure, but decreased the LV end-diastolic pressure (8.8+/-1.8 vs. 4.4+/-0.5 mmHg, P<0.05) in the MI rats. The plasma level of endogenous rat AM in the MI rats infused with human AM was reduced by 27% (P<0.05), with a slight reduction of plasma atrial natriuretic peptide, compared with the control.
Continuous administration of AM had beneficial effects on LV remodeling and hemodynamics in MI rats, suggesting the possibility that this peptide could be a useful therapeutic tool for acute MI.
我们之前报道过，急性心肌梗死（MI）患者血浆肾上腺髓质素（AM）水平升高，且AM可抑制大鼠心肌细胞和成纤维细胞的生长。本研究旨在探讨在MI大鼠模型中，长期给予AM对左心室（LV）重构、血流动力学和激素参数的影响。
通过左冠状动脉结扎诱导MI的大鼠，经渗透微型泵静脉输注1.0微克/小时的重组人AM或生理盐水。输注4周后，进行血流动力学和激素研究，并对非梗死LV区域的心肌细胞大小和胶原体积进行形态计量学定量分析。
与输注生理盐水的MI大鼠相比，持续输注AM可降低心脏重量/体重（4.4±0.2 vs. 3.6±0.1克/千克，P<0.01）、心肌细胞大小（922±23 vs. 868±10微米²，P<0.05）以及非梗死LV区域的胶原体积分数（7.6±0.8 vs. 4.8±0.5%，P<0.05），而不影响梗死面积。AM输注对动脉压无显著影响，但可降低MI大鼠的LV舒张末期压力（8.8±1.8 vs. 4.4±0.5毫米汞柱，P<0.05）。与对照组相比，输注人AM的MI大鼠内源性大鼠AM的血浆水平降低了27%（P<0.05），血浆心房利钠肽略有降低。
持续给予AM对MI大鼠的LV重构和血流动力学有有益影响，提示该肽可能成为急性MI的一种有用治疗工具。
