Department of Medicine, Division of Cardiovascular Disease, UAB.
Department of Pathology, UAB.
J Thorac Cardiovasc Surg. 2016 Oct;152(4):1059-1070.e2. doi: 10.1016/j.jtcvs.2016.06.017. Epub 2016 Jun 25.
Recent studies have demonstrated improved outcomes in patients receiving early surgery for degenerative mitral regurgitation (MR) rather than adhering to conventional guidelines for surgical intervention. However, studies providing a mechanistic basis for these findings are limited.
Left ventricular (LV) myocardium from 22 patients undergoing mitral valve repair for American Heart Association class I indications was evaluated for desmin, the voltage-dependent anion channel, α-B-crystallin, and α, β-unsaturated aldehyde 4-hydroxynonenal by fluorescence microscopy. The same was evaluated in 6 normal control LV autopsy specimens. Cardiomyocyte ultrastructure was examined by transmission electron microscopy. Magnetic resonance imaging with tissue tagging was performed in 55 normal subjects and 22 MR patients before and 6 months after mitral valve repair.
LV end-diastolic volume was 1.5-fold (P < .0001) higher and LV mass-to-volume ratio was lower in MR (P = .004) hearts versus normal hearts and showed improvement 6 months after mitral valve surgery. However, LV ejection fraction decreased from 65% ± 7% to 52% ± 9% (P < .0001) and LV circumferential (P < .0001) and longitudinal strain decreased significantly below normal values (P = .002) after surgery. Hearts with MR had a 53% decrease in desmin (P < .0001) and a 2.6-fold increase in desmin aggregates (P < .0001) versus normal, along with substantial, intense perinuclear staining of α, β-unsaturated aldehyde 4-hydroxynonenal in areas of mitochondrial breakdown and clustering. Transmission electron microscopy demonstrated numerous electron-dense deposits, myofibrillar loss, Z-disc abnormalities, and extensive granulofilamentous debris identified as desmin-positive by immunogold transmission electron microscopy.
Despite well-preserved preoperative LV ejection fraction, severe oxidative stress and disruption of cardiomyocyte desmin-mitochondrial sarcomeric architecture may explain postoperative LV functional decline and further supports the move toward earlier surgical intervention.
最近的研究表明，对于退行性二尖瓣反流（MR）患者，早期手术治疗的效果优于遵循传统手术干预指南。然而，提供这些发现的机制基础的研究有限。
评估 22 例因美国心脏协会 I 类适应证行二尖瓣修复术的患者的左心室（LV）心肌中的结蛋白、电压依赖性阴离子通道、α-B-晶体蛋白和α、β-不饱和醛 4-羟基壬烯醛，采用荧光显微镜。对 6 例正常 LV 尸检标本进行相同评估。采用透射电子显微镜检查心肌细胞超微结构。在 55 例正常受试者和 22 例 MR 患者术前和二尖瓣修复术后 6 个月进行组织标记物心脏磁共振成像。
MR 组的 LV 舒张末期容积增加 1.5 倍（P<0.0001），LV 质量与容积比降低（P=0.004），二尖瓣手术后 6 个月改善。然而，LV 射血分数从 65%±7%下降至 52%±9%（P<0.0001），LV 圆周（P<0.0001）和纵向应变显著低于正常值（P=0.002）。MR 组的结蛋白减少 53%（P<0.0001），结蛋白聚集体增加 2.6 倍（P<0.0001），伴有线粒体破裂和聚集区域中大量、强烈的α、β-不饱和醛 4-羟基壬烯醛的核周染色。透射电子显微镜显示，大量电子致密沉积物、肌节损失、Z 盘异常和广泛的颗粒状纤维状碎片，免疫金透射电子显微镜显示这些碎片为结蛋白阳性。
尽管术前 LV 射血分数保存良好，但严重的氧化应激和肌节结构破坏可能解释术后 LV 功能下降，并进一步支持更早进行手术干预。
