Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Clínico San Carlos, Madrid, Spain.
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Philips Healthcare, Madrid, Spain.
J Am Coll Cardiol. 2015 Feb 3;65(4):315-323. doi: 10.1016/j.jacc.2014.11.004. Epub 2014 Nov 17.
It is widely accepted that edema occurs early in the ischemic zone and persists in stable form for at least 1 week after myocardial ischemia/reperfusion. However, there are no longitudinal studies covering from very early (minutes) to late (1 week) reperfusion stages confirming this phenomenon.
This study sought to perform a comprehensive longitudinal imaging and histological characterization of the edematous reaction after experimental myocardial ischemia/reperfusion.
The study population consisted of 25 instrumented Large-White pigs (30 kg to 40 kg). Closed-chest 40-min ischemia/reperfusion was performed in 20 pigs, which were sacrificed at 120 min (n = 5), 24 h (n = 5), 4 days (n = 5), and 7 days (n = 5) after reperfusion and processed for histological quantification of myocardial water content. Cardiac magnetic resonance (CMR) scans with T2-weighted short-tau inversion recovery and T2-mapping sequences were performed at every follow-up stage until sacrifice. Five additional pigs sacrificed after baseline CMR served as controls.
In all pigs, reperfusion was associated with a significant increase in T2 relaxation times in the ischemic region. On 24-h CMR, ischemic myocardium T2 times returned to normal values (similar to those seen pre-infarction). Thereafter, ischemic myocardium-T2 times in CMR performed on days 4 and 7 after reperfusion progressively and systematically increased. On day 7 CMR, T2 relaxation times were as high as those observed at reperfusion. Myocardial water content analysis in the ischemic region showed a parallel bimodal pattern: 2 high water content peaks at reperfusion and at day 7, and a significant decrease at 24 h.
Contrary to the accepted view, myocardial edema during the first week after ischemia/reperfusion follows a bimodal pattern. The initial wave appears abruptly upon reperfusion and dissipates at 24 h. Conversely, the deferred wave of edema appears progressively days after ischemia/reperfusion and is maximal around day 7 after reperfusion.
人们普遍认为,水肿发生在缺血区早期,并在心肌缺血/再灌注后至少 1 周内以稳定形式持续存在。然而,目前尚无涵盖从非常早期(数分钟)到晚期(1 周)再灌注阶段的纵向研究来证实这一现象。
本研究旨在对实验性心肌缺血/再灌注后水肿反应进行全面的纵向影像学和组织学特征描述。
研究人群包括 25 只植入仪器的大白猪(30 公斤至 40 公斤)。20 只猪进行了 40 分钟的闭胸缺血/再灌注,再灌注后 120 分钟(n=5)、24 小时(n=5)、4 天(n=5)和 7 天(n=5)处死,并对心肌含水量进行组织学定量分析。在每次随访阶段都进行心脏磁共振(CMR)扫描,采用 T2 加权短 tau 反转恢复和 T2 映射序列。另外 5 只在基线 CMR 后处死的猪作为对照。
在所有猪中,再灌注与缺血区 T2 弛豫时间的显著增加相关。在 24 小时 CMR 上,缺血心肌 T2 时间恢复到正常水平(与梗死前相似)。此后,再灌注后 4 天和 7 天 CMR 上的缺血心肌-T2 时间逐渐系统地增加。在 7 天 CMR 时,T2 弛豫时间与再灌注时一样高。缺血区心肌含水量分析显示出双峰模式的平行模式:再灌注时和 7 天时出现 2 个高含水量峰值,24 小时时显著降低。
与公认的观点相反,缺血/再灌注后第一周的心肌水肿呈双峰模式。最初的波在再灌注时突然出现,并在 24 小时时消散。相反,延迟性水肿波在缺血/再灌注后几天逐渐出现,并在再灌注后第 7 天达到最大值。