Pathophysiology Underlying the Bimodal Edema Phenomenon After Myocardial Ischemia/Reperfusion

• Published in: Journal of the American College of Cardiology Vol. 66; no. 7; pp. 816 - 828
• Main Authors: Fernández-Jiménez, Rodrigo, MD, García-Prieto, Jaime, BSc, Sánchez-González, Javier, PhD, Agüero, Jaume, MD, López-Martín, Gonzalo J., RT, Galán-Arriola, Carlos, DVM, Molina-Iracheta, Antonio, DVM, Doohan, Roisin, BSc, Fuster, Valentin, MD, PhD, Ibáñez, Borja, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18-08-2015; Elsevier Limited
• Subjects: Animals; Cardiology; Cardiovascular; Collagen; Edema; Edema - etiology; Edema - physiopathology; healing; Heart attacks; Hemorrhage; Hogs; Hypotheses; Internal Medicine; Ischemia; Laboratory animals; magnetic resonance; Male; myocardial infarction; Myocardial Ischemia - complications; Myocardial Ischemia - physiopathology; Myocardial Reperfusion - adverse effects; Myocardial Reperfusion - methods; Myocardial Reperfusion Injury - etiology; Myocardial Reperfusion Injury - physiopathology; Normal distribution; Studies; Swine; tissue; magnetic resonance; edema; myocardial infarction; collagen; CMR; tissue; I/R; LAD; ischemia/reperfusion; healing; left anterior descending; MI; cardiac magnetic resonance; T2
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2015.06.023

Abstract Background Post-ischemia/reperfusion (I/R) myocardial edema was recently shown to follow a consistent bimodal pattern: an initial wave of edema appears on reperfusion and dissipates at 24 h, followed by a deferred wave that initiates days after infarction, peaking at 1 week. Objectives This study examined the pathophysiology underlying this post-I/R bimodal edematous reaction. Methods Forty instrumented pigs were assigned to different myocardial infarction protocols. Edematous reaction was evaluated by water content quantification, serial cardiac magnetic resonance T2-mapping, and histology/immunohistochemistry. The association of reperfusion with the initial wave of edema was evaluated in pigs undergoing 40-min/80-min I/R and compared with pigs undergoing 120-min ischemia with no reperfusion. The role of tissue healing in the deferred wave of edema was evaluated by comparing pigs undergoing standard 40-min/7-day I/R with animals subjected to infarction without reperfusion (chronic 7-day coronary occlusion) or receiving post-I/R high-dose steroid therapy. Results Characterization of post-I/R tissue changes revealed maximal interstitial edema early on reperfusion in the ischemic myocardium, with maximal content of neutrophils, macrophages, and collagen at 24 h, day 4, and day 7 post-I/R, respectively. Reperfused pigs had significantly higher myocardial water content at 120 min and T2 relaxation times on 120 min cardiac magnetic resonance than nonreperfused animals. Permanent coronary occlusion or high-dose steroid therapy significantly reduced myocardial water content on day 7 post-infarction. The dynamics of T2 relaxation times during the first post-infarction week were altered significantly in nonreperfused pigs compared with pigs undergoing regular I/R. Conclusions The 2 waves of the post-I/R edematous reaction are related to different pathophysiological phenomena. Although the first wave is secondary to reperfusion, the second wave occurs mainly because of tissue healing processes.