Revascularization of hibernating myocardium: uneven reflorescence after the drought.
Revascularization of hibernating myocardium: uneven reflorescence after the drought.
复制标题
冬眠心肌的血运重建：干旱后不均匀的再花。
DOI：
10.1016/j.jacc.2014.12.024
复制
发表时间：
2015
影响因子：
24
通讯作者：
Recchia,FabioA
中科院分区：
文献类型：
--
作者：
Recchia,FabioA
Rahimtoola首先将冬眠心肌定义为“。心肌缺血的长期亚急性或慢性阶段，通常不伴有疼痛，其中心肌收缩力和代谢以及心室功能降低以匹配减少的血液供应”（1）。严重的冠状动脉狭窄是冬眠的主要原因，可以通过血管重建干预部分或完全逆转（2）。在PubMed上以“冬眠心肌”为主题进行的近似检索产生了自1985年以来发表的约500篇研究论文，不包括许多先前和随后的临床和实验研究，这些研究定义和探索了慢性低灌注心肌中发生的特殊变化。尽管发表的研究引人注目，我们掌握的病理生理和分子过程，导致心肌冬眠仍然是有限的。一个尚不清楚的现象是在患者中观察到的功能恢复的变异性，甚至在慢性冬眠心室段的血运重建后数月也是如此（3-4）。这个问题具有重要的预后意义（5）。由于长期低灌注可导致部分坏死/纤维化，因此提出的解释是血运重建后改善的程度高度依赖于存活心肌的残留质量;临床和实验研究表明，透壁坏死/纤维化程度与缺血和缺血后心室壁的收缩功能之间存在线性负相关（4，6，7）。但是，生物学和医学的解释范式往往不是直观和明显的。尽管没有纤维化，但据报道，超过20%的患者在成功血运重建的心室节段中出现持续性收缩功能障碍（4）。这一现象暗示了存活心肌细胞的可能改变，从而对其功能产生负面影响。(8)在本期杂志中，研究人员验证了这样一个假设，即在没有梗死的情况下，持续的心肌细胞损失和/或蛋白质表达改变会影响再血管化冬眠心肌的功能恢复。作者使用了一种优雅且技术上具有挑战性的严重左前降支冠状动脉狭窄猪模型，在3个月内诱导并维持心肌冬眠，随后使用血管内支架完全再通，然后随访1个月。该模型方便地没有坏死/纤维化;然而，在血运重建后1个月，心室壁收缩期增厚仅部分恢复。排除了透壁坏死的作用。那么，血运重建在很大程度上没有推翻细胞的改变吗？令人惊讶的发现是，尽管血管再开放确实导致了许多逆转性变化，但这些变化是非常异质的。一个彻底的蛋白质组学分析显示，以前上调的压力和细胞骨架蛋白，一些收缩蛋白的持续下调，和代谢酶的调节不均匀的变化正常化。其中，丙酮酸的表达
Rahimtoola first defined hibernating myocardium as the “. prolonged subacute or chronic stage of myocardial ischemia that is frequently not accompanied by pain and in which myocardial contractility and metabolism and ventricular function are reduced to match the reduced blood supply”(1). Severe coronary artery stenosis is the primary cause of hibernation, which can be partially or completely reversed by interventions of revascularization (2). An approximate PubMed search on the topic “hibernating myocardium” yields about 500 research papers published since 1985, not including many prior and subsequent clinical and experimental studies that defined and explored the peculiar changes occurring in chronically-hypoperfused myocardium. Despite the conspicuous published studies, our grasp of the pathophysiological and molecular processes leading to myocardial hibernation is still limited. One of the phenomena that remain poorly understood is the variability of functional recovery observed in patients, even months after revascularization of chronically hibernating ventricular segments (3–4). This problem has important prognostic implications (5). Because prolonged hypoperfusion can cause partial necrosis/fibrosis, a proposed explanation is that the degree of post-revascularization improvement is highly dependent on the residual mass of viable myocardium; clinical and experimental studies have shown a linear, inverse correlation between the extent of transmural necrosis/fibrosis and contractile function of ischemic and post-ischemic ventricular walls (4, 6, 7). But, the interpretative paradigms in biology and medicine are very often not intuitive and obvious. Despite the absence of fibrosis, more than 20% of patients were reported to experience persistent contractile dysfunction in successfully revascularized ventricular segments (4). This phenomenon hints at possible alterations to viable cardiomyocytes that negatively affect their function.The study by Page et al.(8) in this issue of the Journal tested the hypothesis that persistent myocyte loss and/or altered protein expression influence the functional recovery of revascularized hibernating myocardium in the absence of infarction. The authors used an elegant and technically-challenging swine model of severe left anterior descending coronary artery stenosis to induce and maintain myocardial hibernation over a period of 3 months, followed by complete recanalization with an intravascular stent, and then 1 month of follow-up. This model was conveniently devoid of necrosis/fibrosis; yet, at 1 month after revascularization, ventricular wall systolic thickening was only partially restored. The role of transmural necrosis was ruled out. So, did revascularization largely fail to overturn cellular alterations? The surprising finding was that, although vessel reopening did lead to numerous reverse changes, these were very heterogeneous. A thorough proteomic analysis revealed normalization of previously upregulated stress and cytoskeletal proteins, persistent down-regulation of some contractile proteins, and nonuniform changes in regulation of metabolic enzymes. Among the latter, the expression of pyruvate