0268: TREM-1 modulation improves cardiac function during myocardial infarction in pigs

Abstract

The widespread use of reperfusion therapy have led to an important improvement in short-term mortality after acute myocardial infarction (MI), but long-term mortality remains high. The Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) belongs to the immunoreceptors superfamily and acts as an amplifier of the inflammatory response triggered by TLRs engagement during both infectious and aseptic inflammatory diseases. We hypothesized that administration of LR12, a synthetic peptide able to inhibit TREM-1 activation, could be beneficial at the acute phase of MI, in a clinically relevant model of experimental MI in pigs. MI was induced in fifteen anesthetized and mechanically ventilated pigs weighing 45–55 kg, by inflation of an angioplasty balloon in the proximal left anterior descending (LAD) coronary artery cannulated under X-ray guidance, during 60 minutes. Fifteen minutes before deflation, animals were randomized to receive either LR12 (n=7) or LR12-scramble (n=8). Complete hemodynamic and functional parameters were monitored through arterial line, swan-ganz and intraventricular conductance catheters. Resuscitation was conducted by experienced intensivists according to standard protocols used in clinical practice. The monitoring was prolonged until H18, then survivors were euthanized. The decrease in mean arterial pressure (MAP) was significantly limited during the monitoring period from H12 to the end (-22.1% vs -3.9%, p<.01). Cardiac index and cardiac power index, one of the strongest hemodynamic correlate of mortality in cardiogenic shock, were preserved under LR12 regimen (72% vs 45% from baseline value, p<.05) as well as SvO2 value (74% vs 62%, p<.05). Ejection fraction and parameters of systolic function improved under LR12 treatment. TREM-1 inhibition by LR12 at the acute phase of myocardial infarction in invasively monitored pigs limits reperfusion injury and alteration of ventricular contractility.