Systemic mapping of organ plasma extravasation at multiple stages of chronic heart failure.

Introduction: Chronic Heart failure (CHF) is a highly prevalent disease that leads to significant morbidity and mortality. Diffuse vasculopathy is a commonmorbidity associated with CHF. Increased vascular permeability leading to plasma extravasation (PEx) occurs in surrounding tissues following endothelial dysfunction. Such micro- and macrovascular complications develop over time and lead to edema, inflammation, and multi-organ dysfunction in CHF. However, a systemic examination of PEx in vital organs among different time windows of CHF has never been performed. In the present study, we investigated time-dependent PEx in several major visceral organs including heart, lung, liver, spleen, kidney, duodenum, ileum, cecum, and pancreas between sham-operated and CHF rats induced by myocardial infarction (MI). Methods: Plasma extravasation was determined by colorimetric evaluation of Evans Blue (EB) concentrations at 3 days, ∼10 weeks and 4 months following MI. Results: Data show that cardiac PEx was initially high at day 3 post MI and then gradually decreased but remained at a moderately high level at ∼10 weeks and 4 months post MI. Lung PEx began at day 3 and remained significantly elevated at both ∼10 weeks and 4 months post MI. Spleen PExwas significantly increased at ∼10 weeks and 4 months but not on day 3 post MI. Liver PEx occurred early at day 3 and remain significantly increased at ∼10 weeks and 4 months post MI. For the gastrointestinal (GI) organs including duodenum, ileum and cecum, there was a general trend that PEx level gradually increased following MI and reached statistical significance at either 10 weeks or 4 months post MI. Similar to GI PEx, renal PEx was significantly elevated at 4 months post MI. Discussion: In summary, we found that MI generally incites a timedependent PEx of multiple visceral organs. However, the PEx time window for individual organs in response to the MI challenge was different, suggesting that different mechanisms are involved in the pathogenesis of PEx in these vital organs during the development of CHF.

引言：慢性心力衰竭（CHF）是一种高发疾病，会导致显著的发病率和死亡率。弥漫性血管病变是与CHF相关的一种常见并发症。在内皮功能障碍后，周围组织会出现血管通透性增加导致血浆渗出（PEx）的情况。这种微血管和大血管并发症会随着时间发展，导致CHF患者出现水肿、炎症和多器官功能障碍。然而，从未对CHF不同时间窗内重要器官的PEx进行过系统检查。在本研究中，我们研究了假手术组和心肌梗死（MI）诱导的CHF大鼠在心脏、肺、肝、脾、肾、十二指肠、回肠、盲肠和胰腺等几个主要内脏器官中随时间变化的PEx情况。 方法：在MI后3天、约10周和4个月时，通过比色法评估伊文思蓝（EB）浓度来测定血浆渗出情况。 结果：数据显示，心脏PEx在MI后第3天最初较高，然后逐渐降低，但在MI后约10周和4个月时仍处于中等偏高水平。肺PEx在第3天开始出现，并在MI后约10周和4个月时仍显著升高。脾PEx在MI后约10周和4个月时显著增加，但在第3天没有增加。肝PEx在第3天早期出现，并在MI后约10周和4个月时仍显著增加。对于包括十二指肠、回肠和盲肠在内的胃肠（GI）器官，总体趋势是MI后PEx水平逐渐升高，并在MI后10周或4个月时达到统计学意义。与胃肠PEx类似，肾PEx在MI后4个月时显著升高。 讨论：总之，我们发现MI通常会引发多个内脏器官的时间依赖性PEx。然而，单个器官对MI刺激的PEx时间窗不同，这表明在CHF发展过程中，这些重要器官中PEx的发病机制涉及不同的机制。