Dexamethasone Alleviates Myocardial Injury in a Rat Model of Acute Myocardial Infarction Supported by Venoarterial Extracorporeal Membrane Oxygenation

Abstract

Myocardial ischemia causes myocardial inflammation. Research indicates that the venoarterial extracorporeal membrane oxygenation (VA ECMO) provides cardiac support; however, the inflammatory response caused by myocardial ischemia remains unresolved. Dexamethasone (Dex), a broad anti-inflammatory agent, exhibits a cardioprotective effect. This study aims to investigate the effect of Dex on a rat model of acute myocardial infarction (AMI) supported by VA ECMO. Male Sprague-Dawley rats (300-350 g) were randomly divided into three groups: Sham group (n = 5), ECMO group (n = 6), and ECMO + Dex group (n = 6). AMI was induced by ligating the left anterior descending (LAD) coronary artery. Sham group only thoracotomy was performed but LAD was not ligated. The ECMO and ECMO + Dex groups were subjected to 1 h of AMI and 2 h of VA ECMO. In the ECMO + Dex group, Dex (0.2 mg/kg) was intravenously injected into the rats after 1 h of AMI. Lastly, myocardial tissue and blood samples were harvested for further evaluation. The ECMO + Dex group significantly reduced infarct size and levels of cTnI, cTnT, and CK-MB. Apoptotic cells and the expression levels of Bax, Caspase3, and Cle-Caspase3 proteins were markedly lower in the ECMO + Dex group than that in the ECMO group. Neutrophil and macrophage infiltration was lower in the ECMO + Dex group than in the ECMO group. A significant reduction was noted in ICAM-1, C5a, MMP-9, IL-1β, IL-6, and TNF-α. In summary, our findings revealed that Dex alleviates myocardial injury in a rat model of AMI supported by VA ECMO.

Keywords: acute myocardial infarction; apoptosis; dexamethasone; inflammatory response; venoarterial extracorporeal membrane oxygenation.

Figure 1

Flow chart and schematic diagram of experimental operation. (A) Flow chart of the establishment of experimental models. (B) Schematic diagram of the application of Dex in a rat model of AMI supported by VA ECMO.

Figure 2

Dynamic changes of mean arterial pressure (MAP) in each group throughout the operation. **p < 0.01 vs. the ECMO group.

Figure 3

Dex treatment attenuated myocardial injury. (A,B) Representative TTC staining images and quantitative analysis in each group. (C) Representative H&E staining images in each group. Scale bar: 50 μm. Arrows indicate contraction band necrosis. (D–F) The concentrations of cardiac injury markers cTnI, cTnT, and CK-MB in the serum. Data are expressed as mean ± SD. **p < 0.01, ***p < 0.001 vs. the ECMO group.

Figure 4

Dex treatment reduced myocardial apoptosis. (A,B) Representative TUNEL staining images and quantitative data in each group. (C,D) Representative images of Western Blot analysis in each group. (E–I) Relative expression levels of Bcl-2, Bax, Caspase3, and Cleaved Caspase3 in each group. Data are expressed as mean ± SD. **p < 0.01, ***p < 0.001 vs. the ECMO group.

Figure 5

Dex treatment reduced chemotaxis effect and inflammatory response. (A–D) Representative images and quantitative data of neutrophils and macrophagocyte infiltrations. Scale bar: 50 μm. Arrows indicate neutrophils and macrophagocyte infiltrations. (E–G) The levels of chemokines ICAM-1, C5a, and MMP-9 for heart tissues in each group. (H–J) The levels of inflammatory factors IL-1β, IL-6, and TNF-α for heart tissues in each group. Data are expressed as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001 vs. the ECMO group.