Characterization and implications of the dynamics of eosinophils in blood and in the infarcted myocardium after coronary reperfusion.

Cesar Rios-Navarro,Clara Bonanad,Veronica Vidal,Paolo Racugno,Antoni Bayes-Genis,Julio Nuñez,Amparo Ruiz-Sauri,Jose Gavara,Vicente Bodi,Francisco J Chorro,Ricardo Oltra,Oliver Husser,Gema Miñana

doi:10.1371/journal.pone.0206344

Abstract

ObjectiveWe characterized the dynamics of eosinophils in blood and in the infarcted myocardium in patients and in a swine model of reperfused myocardial infarction (MI). The association of eosinophil dynamics with various outcomes was assessed.MethodsSerial eosinophil count and pre-discharge cardiac magnetic resonance were carried out in a prospective series of 620 patients with a first ST-elevation MI. In a swine model of reperfused MI, the dynamics of circulating eosinophils and their presence in the infarcted myocardium were determined. In autopsies from chronic MI patients, eosinophils were quantified.ResultsPatient eosinophil count sharply decreased 12h post-reperfusion compared to arrival. A lower minimum eosinophil count was associated with more extensive edema, microvascular obstruction, and infarct size as measured by cardiac magnetic resonance, and also with a higher rate of cardiac events (death, re-infarction, or heart failure) during follow-up. In the experimental model, eosinophil count boosted during ischemia and dropped back immediately post-reperfusion. Myocardial samples revealed progressive eosinophil migration into the infarcted myocardium, especially areas with microvascular obstruction. Markers of eosinophil maturation and survival (interleukin-5), degranulation (eosinophil cationic protein) and migration (eotoxin-1) were detected in the blood of patients, and in porcine myocardium. Eosinophil infiltration was detected in autopsies from chronic MI patients.ConclusionEosinopenia post-MI was associated with an impaired cardiac structure and adverse events. The decay in circulating eosinophils soon after reperfusion mirrors their migration into the infarcted myocardium, as reflected by their presence in heart samples from swine and patients. Further studies are needed to understanding this unexplored pathway and its therapeutic implications.

Highlights

Eosinophils are granulocytic leukocytes that play an essential role in allergic reactions, asthma, and parasitic infections
A lower minimum eosinophil count was associated with more extensive edema, microvascular obstruction, and infarct size as measured by cardiac magnetic resonance, and with a higher rate of cardiac events during follow-up
To investigate the association between eosinophils and outcomes, we focused on the following specific objectives: 1) To analyse serial eosinophil cell count in peripheral blood of reperfused segment elevation myocardial infarction (STEMI) patients and determine its association with cardiac magnetic resonance (CMR)-derived edema, microvascular obstruction (MVO), and infarct size as well as with the occurrence of major adverse cardiac events (MACE) during follow-up

Summary

Introduction

Eosinophils are granulocytic leukocytes that play an essential role in allergic reactions, asthma, and parasitic infections. Eosinophils normally account for only 1–3% of circulating leukocytes, the number of both peripheral and tissue eosinophils are markedly altered in some inflammatory reactions [1,2,3,4]. Eosinophils quickly degranulate and release potent factors to promote protective immunity, coagulation, and platelet aggregation [2]. They can be recruited into an inflammatory focus to modulate the immune response [3,4]. The role of fluctuations in neutrophil and monocyte cell counts and, more recently, in lymphocyte subsets (both in peripheral blood and in the infarcted myocardium) have been widely addressed in this scenario [5,6,7,8]

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