Experimental and pre-clinical data suggest that in acute myocardial infarction (AMI) a loss of control of the immune system takes place in part driven by a decrease of lymphocyte count. The aim of this study is to investigate this pathophysiological process and its association with infarct-derived structural damage.Methods
In thirty patients with a first reperfused ST-segment elevation AMI and thirty subjects with normal coronary arteries diagnosed by angiography we serially determined different mononuclear cells and cytokines before and 24, 96 hours and 30 days after reperfusion. These parameters were also serially assessed in 20 swine with anterior AMI induced by balloon inflation in the left anterior descending artery. Inflammatory parameters were related to infarct size and microvascular obstruction (MVO) assessed by cardiac magnetic resonance in humans and by histopathological analysis in swine.Results
Patients with less infarct size and no MVO showed a decrease in lymphocyte count within the first 24 hours in part due to lymphocyte apoptosis (p < 0,05). Lymphopenia was mainly driven by T cell loss (p < 0.01), while B cell number kept constant. A significant decrease of pro-inflammatory Th1 cells and IFN-γ opposite to an increase of anti-inflammatory TGF-β took place (p < 0.01). We also observed a significant loss of aggressive cells, NK, CD8 + and T effector memory cells; however T regulatory cells progressively increased (p < 0.05 in all cases). CD4 cells count recovery 96 hours after reperfusion associated to a smaller infarct size and less MVO extent (p < 0,05). In swine we observed lymphopenia 1 hour after coronary occlusion (p < 0,05); a decrease of aggressive (CD8) and memory (CD4CD8) cells response 2 hours after reperfusion related to less infarct size and MVO extent. Histopathological analysis showed severe CD3 myocardial infiltration in swine with bigger infarctions.Conclusions
In reprefused AMI, acute loss of pro-inflammatory cell subsets seems to downgrade the immune system towards a less aggressive response. Apoptosis and infiltration of the infarcted area by t cells explain, at least in part, acute lymphopenia in reperfused AMI. In post-acute phase of AMI patients whom didn't recovered from lymphopenia showed a worst prognosis.