Open AccessPharmacological inhibition of the triggering receptor expressed on myeloid cells‐1 limits reperfusion injury in a porcine model of myocardial infarction
Author(s) -
Lemarié Jérémie,
Boufenzer Amir,
Popovic Batric,
Tran Nguyen,
Groubatch Frederique,
Derive Marc,
Labroca Pierre,
Barraud Damien,
Gibot Sébastien
Publication year - 2015
Publication title -
esc heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.787
H-Index - 25
ISSN - 2055-5822
DOI - 10.1002/ehf2.12029
Subject(s) - medicine , reperfusion injury , myocardial infarction , cardiology , ejection fraction , creatine kinase , cardiac function curve , cardioprotection , ischemia , heart failure
Aims Limitation of ischemia/reperfusion injury is a major therapeutic target after acute myocardial infarction (AMI). Toll‐like receptors are implicated in the inflammatory response that occurs during reperfusion. The triggering receptor expressed on myeloid cells (TREM)‐1 acts as an amplifier of the immune response triggered by toll‐like receptor engagement. We hypothesized that administration of a TREM‐1 inhibitory peptide (LR12) could limit reperfusion injury in a porcine model of AMI. Methods and results AMI was induced in 15 adult minipigs by a closed‐chest coronary artery occlusion‐reperfusion technique. Animals were randomized to receive LR12 or vehicle before reperfusion (LR12 n = 7, vehicle n = 8), and were monitored during 18 h. AMI altered hemodynamics and cardiac function, as illustrated by a drop of mean arterial pressure, cardiac index, cardiac power index, ejection fraction, and real‐time pressure–volume loop‐derived parameters. TREM‐1 inhibition by LR12 significantly improved these dysfunctions ( P < 0.03) and limited infarct size, as assessed by lower creatine phosphokinase and troponin I concentrations ( P < 0.005). Pulmonary, renal, and hepatic impairments occurred after AMI and were attenuated by LR12 administration as assessed by a better PaO 2 to FiO 2 ratio, a less positive fluid balance, and lower liver enzymes levels ( P < 0.05). Conclusion Inhibition of the TREM‐1 pathway by a synthetic peptide limited myocardial reperfusion injury in a clinically relevant porcine model of AMI.