Pathophysiology Underlying the Bimodal Edema Phenomenon After Myocardial Ischemia/Reperfusion.
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.


OBJECTIVE
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.
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; Hospital Universitario Clínico San Carlos, Madrid, Spain.
Rodrigo
R
Fernández-Jiménez
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Jaime
J
García-Prieto
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; Philips Healthcare, Madrid, Spain.
Javier
J
Sánchez-González
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Jaume
J
Agüero
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Gonzalo J
GJ
López-Martín
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Carlos
C
Galán-Arriola
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Antonio
A
Molina-Iracheta
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Roisin
R
Doohan
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York.
Valentin
V
Fuster
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; Hospital Universitario Clínico San Carlos, Madrid, Spain. Electronic address: bibanez@cnic.es.
Borja
B
Ibáñez
D000818:Animals; D004487:Edema / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D015425:Myocardial Reperfusion / Q000009:adverse effects / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology*; D013552:Swine
T2; collagen; edema; healing; magnetic resonance; myocardial infarction; tissue