Pathophysiology underlying the bimodal edema phenomenon after myocardial ischemia/reperfusion

Rodrigo Fernández-Jiménez, Jaime García-Prieto, Javier Sánchez-González, Jaume Agüero, Gonzalo J. López-Martín, Carlos Galán-Arriola, Antonio Molina-Iracheta, Roisin Doohan, Valentin Fuster, Borja Ibáñez

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115 Scopus citations

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.

Original languageEnglish
Pages (from-to)816-828
Number of pages13
JournalJournal of the American College of Cardiology
Volume66
Issue number7
DOIs
StatePublished - 18 Aug 2015

Keywords

  • T2
  • collagen
  • edema
  • healing
  • magnetic resonance
  • myocardial infarction
  • tissue

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