Reperfused hemorrhagic myocardial infarction in rats.
Reperfused hemorrhagic myocardial infarction in rats.
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大鼠出血性心肌梗死再灌流模型。
DOI：
10.1371/journal.pone.0243207
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Dharmakumar R
中科院分区：
文献类型：
--
作者：
Nair AR;Johnson EA;Yang HJ;Cokic I;Francis J;Dharmakumar R
再灌注后的心肌内出血与心肌梗死（MI）患者的主要不良心血管事件密切相关；然而，促成这些结果的机制尚不清楚。大型动物模型已被用来研究心肌内出血，但它们非常昂贵并且难以用于机制研究。相比之下，大鼠模型被广泛用于研究心血管生理学的机制方面，但一致概括出血性心肌梗死特征的大鼠模型并不存在。为了弥补这一差距，我们研究了导致大鼠心肌内出血的心肌梗死的生理条件，以便为基础研究提供可靠的出血性心肌梗死模型。 Sprague-Dawley 大鼠的左冠状动脉前降支经历 90 分钟 (90 分钟) 缺血再灌注 (I/R) (n = 22) 或 30 分钟 (30 分钟) I/R (n = 18)。假手术大鼠（n = 12）用作对照。 90 分钟 I/R 始终产生出血性 MI，而 30 分钟 I/R 始终产生非出血性 MI。再灌注后 24 小时，对 90 分钟 I/R 大鼠的离体心脏进行离体晚期钆增强 (LGE) 和 T2* 心脏 MRI，显示铁沉积物在疤痕组织内共定位；然而，在 30 分钟的 I/R 大鼠中，LGE 上有明显的疤痕，但 T2* CMR 上没有发现铁的证据。组织学研究验证了 LGE 上检测到的组织损伤 (H&E) 以及 T2*-CMR 上观察到的铁（Perl 染色）的存在。再灌注后第 4 周，与 30 分钟 I/R 组相比，90 分钟 I/R 组中促炎标志物（TNF-α、IL-1β 和 MMP-9）的基因和蛋白表达有所增加。此外，对 90 分钟 I/R 心肌进行透射电子显微镜检查，T2* CMR 和 Perl 染色呈铁阳性，显示吞噬体内有颗粒状铁颗粒积累。再灌注前的缺血时间是确定大鼠心肌梗死是出血性还是非出血性的关键因素。具体来说，再灌注前90分钟的缺血可以产生出血性MI的大鼠模型，而再灌注前30分钟的缺血可以确保MI是非出血性的。与非出血性心肌梗死大鼠相比，出血性心肌梗死大鼠会导致铁沉积、促炎负荷和不良左心室重构显着增加。
Intramyocardial hemorrhage following reperfusion is strongly associated with major adverse cardiovascular events in myocardial infarction (MI) patients; yet the mechanisms contributing to these outcomes are not well understood. Large animal models have been used to investigate intramyocardial hemorrhage, but they are exorbitantly expensive and difficult to use for mechanistic studies. In contrast, rat models are widely used to investigate mechanistic aspects of cardiovascular physiology, but a rat model that consistently recapitulates the characteristics of an hemorrhagic MI does not exist. To bridge this gap, we investigated the physiological conditions of MI that would create intramyocardial hemorrhage in rats so that a reliable model of hemorrhagic MI would become available for basic research. Sprague-Dawley rats underwent either a 90-minute (90-min) ischemia and then reperfusion (I/R) (n = 22) or 30-minute (30-min) I/R (n = 18) of the left anterior descending coronary artery. Sham rats (n = 12) were used as controls. 90-min I/R consistently yielded hemorrhagic MI, while 30-min I/R consistently yielded non-hemorrhagic MI. Twenty-four hours post-reperfusion, ex-vivo late-gadolinium-enhancement (LGE) and T2* cardiac MRI performed on excised hearts from 90-min I/R rats revealed colocalization of iron deposits within the scarred tissue; however, in 30-min I/R rats scar was evident on LGE but no evidence of iron was found on T2* CMR. Histological studies verified tissue damage (H&E) detected on LGE and the presence of iron (Perl’s stain) observed on T2*-CMR. At week 4 post-reperfusion, gene and protein expression of proinflammatory markers (TNF-α, IL-1β and MMP-9) were increased in the 90-min I/R group when compared to 30-min I/R groups. Further, transmission electron microscopy performed on 90-min I/R myocardium that were positive for iron on T2* CMR and Perl’s stain showed accumulation of granular iron particles within the phagosomes. Ischemic time prior to reperfusion is a critical factor in determining whether a MI is hemorrhagic or non-hemorrhagic in rats. Specifically, a period of 90-min of ischemia prior to reperfusion can produce rat models of hemorrhagic MI, while 30-minutes of ischemia prior to reperfusion can ensure that the MIs are non-hemorrhagic. Hemorrhagic MIs in rats result in marked increase in iron deposition, proinflammatory burden and adverse left—ventricular remodeling compared to rats with non-hemorrhagic MIs.
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DOI：
10.1016/b978-0-12-394309-5.00006-7
发表时间：
2012
影响因子：
--
作者：
Kalogeris, Theodore;Baines, Christopher P.;Krenz, Maike;Korthuis, Ronald J.
通讯作者：
Korthuis, Ronald J.
DOI：
10.1161/circimaging.113.001541
发表时间：
2014-05
期刊：
Circulation. Cardiovascular imaging
影响因子：
--
作者：
Kali A;Cokic I;Tang RL;Yang HJ;Sharif B;Marbán E;Li D;Berman DS;Dharmakumar R
通讯作者：
Dharmakumar R
影响因子：
3.3
作者：
Ghugre, Nilesh R.;Ramanan, Venkat;Wright, Graham A.
通讯作者：
Wright, Graham A.
DOI：
10.1161/circoutcomes.118.005355
发表时间：
2019-05-01
影响因子：
6.9
作者：
Bricker, Rory S.;Valle, Javier A.;Waldo, Stephen W.
通讯作者：
Waldo, Stephen W.
DOI：
10.1152/ajpheart.00286.2007
发表时间：
2007-07-01
影响因子：
4.8
作者：
Guggilam, Anuradha;Haque, Masudul;Francis, Joseph
通讯作者：
Francis, Joseph