Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Alabama at Birmingham, Cardiovascular Institute, Birmingham, Alabama.
Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Department of Veterans Affairs Medical Center, Birmingham VA Health Care System, Birmingham, Alabama.
Ann Thorac Surg. 2023 Oct;116(4):834-843. doi: 10.1016/j.athoracsur.2022.02.084. Epub 2022 Apr 7.
Patients with valvular heart disease require cardiopulmonary bypass and cardiac arrest. Here, we test the hypothesis that exosomal hemoglobin formed during cardiopulmonary bypass mediates acute cardiac injury in humans and in an animal model system.
Plasma exosomes were collected from arterial blood at baseline and 30 minutes after aortic cross-clamp release in 20 patients with primary mitral regurgitation and 7 with aortic stenosis. These exosomes were injected into Sprague-Dawley rats and studied at multiple times up to 30 days. Tissue was examined by hematoxylin and eosin stain, immunohistochemistry, transmission electron microscopy, and brain natriuretic peptide.
Troponin I levels increased from 36 ± 88 ng/L to 3622 ± 3054 ng/L and correlated with exosome hemoglobin content (Spearman r = 0.7136, < .0001, n = 24). Injection of exosomes isolated 30 minutes after cross-clamp release into Sprague-Dawley rats resulted in cardiomyocyte myofibrillar loss at 3 days. Transmission electron microscopy demonstrated accumulation of electron dense particles of ferritin within cardiomyocytes, in the interstitial space, and within exosomes. At 21 days after injection, there was myofibrillar and myosin breakdown, interstitial fibrosis, elevated brain natriuretic peptide, and left ventricle diastolic dysfunction measured by echocardiography/Doppler. Pericardial fluid exosomal hemoglobin content is fourfold higher than simultaneous plasma exosome hemoglobin, suggesting a cardiac source of exosomal hemoglobin.
Red blood cell and cardiac-derived exosomal hemoglobin may be involved in myocardial injury during cardiopulmonary bypass in patients with valvular heart disease.
患有瓣膜性心脏病的患者需要心肺旁路和心脏骤停。在这里，我们检验了这样一个假设，即在心肺旁路过程中形成的细胞外体血红蛋白介导了人类和动物模型系统中的急性心脏损伤。
从 20 例原发性二尖瓣反流和 7 例主动脉瓣狭窄患者的动脉血中在主动脉夹闭释放后基线和 30 分钟时收集血浆细胞外体。将这些细胞外体注射到 Sprague-Dawley 大鼠中，并在多达 30 天的多个时间点进行研究。通过苏木精和伊红染色、免疫组织化学、透射电子显微镜和脑钠肽检查组织。
肌钙蛋白 I 水平从 36±88ng/L 增加到 3622±3054ng/L，并与细胞外体血红蛋白含量相关（Spearman r=0.7136，<0.0001，n=24）。在夹闭释放后 30 分钟从 Sprague-Dawley 大鼠中分离出的细胞外体注射到大鼠中，导致 3 天后心肌细胞肌原纤维丢失。透射电子显微镜显示铁蛋白的电子致密颗粒在心肌细胞内、间质空间内和细胞外体中积聚。注射后 21 天，出现肌原纤维和肌球蛋白分解、间质纤维化、脑钠肽升高以及超声心动图/多普勒测量的左心室舒张功能障碍。心包液细胞外体血红蛋白含量比同时的血浆细胞外体血红蛋白高四倍，表明细胞外体血红蛋白的心脏来源。
在瓣膜性心脏病患者的心肺旁路过程中，红细胞和心脏来源的细胞外体血红蛋白可能参与心肌损伤。
