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冬眠心肌:病理生理学、诊断与治疗

Hibernating myocardium: pathophysiology, diagnosis, and treatment.

作者信息

Slezak Jan, Tribulova Narcis, Okruhlicova Ludmila, Dhingra Rimpy, Bajaj Anju, Freed Darren, Singal Pawan

机构信息

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada.

出版信息

Can J Physiol Pharmacol. 2009 Apr;87(4):252-65. doi: 10.1139/Y09-011.

Abstract

Comprehensive management of patients with chronic ischemic disease is a critically important component of clinical practice. Cardiac myocytes have the potential to adapt to limited flow conditions by adjusting contractile function, reducing metabolism, conserving resources, and preserving myocardial integrity to cope with an oxygen and (or) nutrition shortage. A prime metabolic feature of cardiac myocytes affected by chronic ischemia is the return to a fetal gene pattern with predominance of carbohydrates as the substrate for energy. Structural adaptation with multiple intracellular changes is part of the remodeling process in hibernating myocardium. Transmural heterogeneity, which defines the pattern of injury in ventricular cardiomyocytes and the response to chronic ischemia, is a multifactorial process originating from functional, metabolic, and flow differences in subendocardial and subepicardial regions. Autophagy is typically activated in hibernating myocardium and has been identified as a prosurvival mechanism. Chronic ischemia is associated with changes in the number, size, and distribution of gap junctions and may give rise to conduction disturbances and arrhythmogenesis. Differentiation between viable and nonviable myocardium by assessing sensitivity of inotropic reserve is a crucial diagnostic tool that is correlated with the prognosis and outcome for improved contractility after restoration of blood perfusion in afflicted myocardium.Reliable and accurate diagnosis of ischemic, scar, and viable tissues is critical for recover strategies. Although early surgical reinstitution of blood flow is most effective in restoring physiologic function of the hibernating myocardium, several new approaches offer promising alternatives. Among others, vascular endothelial growth factor and fibroblast growth factor-2 (FGF-2), especially its lo-FGF-2 isoform, have been shown to be effective in rapid neovascularization. Substances such as statins, resveratrol, some hormones, and omega-3 fatty acids can improve recovery effect in chronically underperfused hearts. For patients with drug-refractory ischemia, intramyocardial transplantation of stem cells into predefined areas of the heart can enhance vascularization and have beneficial effects on cardiac function. This review of ischemic injury, its heterogeneity, accurate diagnosis, and newer methods of treatment, shows there is much information and tremendous hope for better management of patients with coronary heart disease.

摘要

慢性缺血性疾病患者的综合管理是临床实践的一个极其重要的组成部分。心肌细胞有潜力通过调节收缩功能、降低代谢、保存资源以及维持心肌完整性来适应有限的血流状况,以应对氧气和(或)营养物质短缺。受慢性缺血影响的心肌细胞的一个主要代谢特征是回归到以碳水化合物作为能量底物的胎儿基因模式。伴有多种细胞内变化的结构适应是冬眠心肌重塑过程的一部分。透壁异质性定义了心室心肌细胞的损伤模式以及对慢性缺血的反应,是一个源于心内膜下和心外膜下区域功能、代谢和血流差异的多因素过程。自噬通常在冬眠心肌中被激活,并已被确定为一种促生存机制。慢性缺血与缝隙连接的数量、大小和分布变化有关,可能导致传导障碍和心律失常的发生。通过评估变力性储备的敏感性来区分存活心肌和非存活心肌是一种关键的诊断工具,它与受累心肌恢复血流灌注后改善收缩性的预后和结果相关。对缺血、瘢痕和存活组织进行可靠而准确的诊断对于恢复策略至关重要。尽管早期手术恢复血流对恢复冬眠心肌的生理功能最有效,但一些新方法提供了有前景的替代方案。其中,血管内皮生长因子和成纤维细胞生长因子 -2(FGF -2),尤其是其低分子量FGF -2异构体,已被证明在快速血管新生方面有效。他汀类药物、白藜芦醇、一些激素和ω-3脂肪酸等物质可以改善长期灌注不足心脏的恢复效果。对于药物难治性缺血患者,将干细胞心肌内移植到心脏的预定区域可以增强血管生成并对心脏功能产生有益影响。这篇关于缺血性损伤、其异质性、准确诊断和新治疗方法的综述表明,对于更好地管理冠心病患者有很多信息和巨大希望。

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