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在缺血条件下,肌心筋伸展诱导的顺应性被废除,并通过cGMP/PKG相关途径恢复
André M Leite-Moreira1,2, João Almeida-Coelho1, João S Neves1,3
1Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal.
Frontiers in physiology
|October 18, 2023
概括
心肌梗塞损害了拉伸诱导的服从性,但固酶-5抑制剂可以恢复这种反应,在体积负荷期间改善心脏功能.
科学领域:
- 心脏病学 心脏病学
- 生理学 生理学 生理学
背景情况:
- 急性心肌梗塞 (MI) 管理需要仔细的液体优化,平衡血流与堵塞风险.
- 伸展诱导合规性 (SIC) 是对心肌伸展的适应性反应,部分由cGMP/cGMP依赖蛋白激酶 (PKG) 途径介导.
研究的目的:
- 为了调查SIC是否在MI中受损.
- 为了确定PKG激活是否可以恢复SIC在MI.
- 评估固酶-5抑制剂 (PDE5i) 的治疗潜力,以改善心脏对MI后体积负荷的反应.
主要方法:
- 实验是在缺血和非缺血条件下对ex vivo子乳房肌肉进行的.
- 在体内研究涉及试验诱导MI的老鼠的压力-体积血动力评估.
- 使用了包括PKG激动剂,PKC激动剂,西尔代纳菲尔 (一种PDE5i),B型尿素和氧化捐赠剂在内的药理学药物.
主要成果:
- 激烈拉伸肌肉在体外增加了服从性,但在缺血条件下,这种效应被取消了.
- 基激动剂和PDE5i在缺血性肌肉中部分恢复了SIC,这种效果在与BNP或氧化捐赠者同时使用时得到放大.
- 在体内,体积加载后的MI仅在注入PDE5i的老鼠中增加了心脏输出,这也表明心肌顺应性得到改善.
结论:
- 缺血会损害心肌适应性应对急性拉伸的反应.
- 通过cGMP/PKG通路,特别是通过PDE5i,可以预防这种损伤.
- 对cGMP/PKG通路的药理学操纵显示出改善急性心肌缺血的临床结果的潜力.
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