Schwenke Daryl O, Tokudome Takeshi, Kishimoto Ichiro, Horio Takeshi, Shirai Mikiyasu, Cragg Patricia A, Kangawa Kenji
Department of Physiology, University of Otago, Dunedin, New Zealand.
Endocrinology. 2008 Oct;149(10):5172-6. doi: 10.1210/en.2008-0472. Epub 2008 Jul 3.
Acute myocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (CSNA), which ultimately exacerbates chronic cardiac dysfunction. Ghrelin (Ghr), a GH-releasing peptide, is an effective treatment for improving cardiac function in chronic heart failure. Ghr also suppresses renal sympathetic nerve activity (SNA) and, therefore, may have important therapeutic benefits in the early stages of acute MI: by reducing CSNA. In this study we hypothesized that early Ghr administration may prevent an increase in CSNA in the acute phase after MI. CSNA was continuously recorded in urethane-anaesthetized rats before and for 5 h after acute MI (or sham). MI was induced by ligation of the left anterior descending coronary artery. Rats received an injection of either saline or Ghr (150 microg/kg, sc) 1 min, or 2 h, after the infarct. CSNA remained stable during the 5-h recording duration in sham rats. MI induced a maximal 110% increase in SNA, which was prevented in rats that received Ghr 1 min after infarct. When Ghr was injected 2 h after MI (SNA had increased by approximately 85%), SNA decreased to pre-MI activity. Importantly, early Ghr administration significantly reduced the high mortality rate associated with MI (61% mortality in untreated MI rats cf. approximately 23% in Ghr-treated MI rats). These results show that early Ghr treatment prevents the increase in CSNA after MI, which may contribute to the improved chances of survival. Whether these early beneficial effects of Ghr also have long-term benefits for improving cardiac function is an area that requires further investigation.
急性心肌梗死（MI）会引发心脏交感神经活动（CSNA）增加，最终加剧慢性心功能不全。胃饥饿素（Ghr）是一种促生长激素释放肽，是改善慢性心力衰竭心功能的有效治疗方法。Ghr还可抑制肾交感神经活动（SNA），因此，在急性心肌梗死早期可能具有重要的治疗益处：通过降低CSNA。在本研究中，我们假设早期给予Ghr可能预防心肌梗死后急性期CSNA的增加。在急性心肌梗死（或假手术）前及术后5小时，持续记录乌拉坦麻醉大鼠的CSNA。通过结扎左冠状动脉前降支诱导心肌梗死。在梗死1分钟或2小时后，大鼠接受生理盐水或Ghr（150μg/kg，皮下注射）注射。假手术大鼠在5小时记录期内CSNA保持稳定。心肌梗死使SNA最大增加110%，而在梗死1分钟后接受Ghr的大鼠中这一增加得到预防。当在心肌梗死后2小时注射Ghr（SNA已增加约85%）时，SNA降至心肌梗死前水平。重要的是，早期给予Ghr显著降低了与心肌梗死相关的高死亡率（未治疗的心肌梗死大鼠死亡率为61%，而Ghr治疗的心肌梗死大鼠约为23%）。这些结果表明，早期Ghr治疗可预防心肌梗死后CSNA的增加，这可能有助于提高生存几率。Ghr的这些早期有益作用是否对改善心功能也有长期益处，是一个需要进一步研究的领域。
