1st Department of Cardiology, University Hospital of Ioannina, 45500 Ioannina, Greece.
Cardiovascular Research Institute, 45500 Ioannina, Greece.
Int J Mol Sci. 2020 Jan 30;21(3):918. doi: 10.3390/ijms21030918.
Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models have demonstrated attenuated dilatation and improved systolic function after growth hormone administration. In addition to ameliorating wall-stress and preserving the peri-infarct myocardium, antiarrhythmic actions were also evident after such treatment, but the precise underlying mechanisms remain poorly understood. The present article summarizes the acute and chronic actions of systemic and local growth hormone administration in the post-infarction setting, placing emphasis on the electrophysiologic effects. Experimental and clinical data are reviewed, and hypotheses on potential mechanisms of action are discussed. Such information may prove useful in formulating new research questions and designing new studies that are expected to increase the translational value of growth hormone therapy after acute myocardial infarction.
心肌梗死仍然是一个主要的与健康相关的问题，具有显著的急性和长期后果。急性冠状动脉闭塞导致明显的电生理改变，可诱发室性心动过速或心室颤动等室性心律失常，常预示着心源性猝死。在梗死愈合阶段，血流动力学和结构变化可导致左心室扩张和功能障碍，而伴随的纤维化则形成折返环的基质，可维持室性心动过速。相当一部分此类患者临床上表现为明显的心力衰竭，这是一种与高发病率和死亡率相关的常见疾病实体。有几条证据表明，生长激素/胰岛素样生长因子-1 轴在梗死后结构和电生理重构的病理生理学中起着关键作用。基于这一原理，动物模型的实验研究表明，生长激素给药后可减轻扩张并改善收缩功能。除了减轻壁应力和保护梗死周边心肌外，这种治疗后还显示出抗心律失常作用，但确切的潜在机制仍知之甚少。本文总结了系统和局部生长激素给药在梗死后的急性和慢性作用，重点介绍电生理效应。回顾了实验和临床数据，并讨论了潜在作用机制的假设。这些信息可能有助于制定新的研究问题和设计新的研究，预计将增加急性心肌梗死后生长激素治疗的转化价值。
