Abstract 3475: Transient Circulating Neutrophil Activation in Patients at the Very Onset of Myocardial Infarction
Purpose: To investigate neutrophil activation in patients at the very onset of acute myocardial infarction (AMI).
Methods: We assessed leukocyte activation in 18 patients with AMI within 6 hours from symptom onset and minimal elevation of markers of myocardial necrosis (Trop I = 4.1±1.4 μg/ml), in 21 patients with chronic stable angina and severe coronary atherosclerosis (CSA) and in 25 healthy controls (C). Myeloperoxidase (MPO), fibrinogen, conversion of Mac-1 to the active conformation and circulating neutrophil-platelet aggregates were analysed by three colour flow cytometry and confocal microscopy in venous blood.
Results: Neutrophil content of MPO was markedly reduced in patients with AMI (mean±SEM; 62.4±5.2 vs C 134.1±5.4 and CSA 137.2±4.5 AUF, p<0.01). In AMI, 10.0±3.8% of neutrophils showed complete degranulation (C 0.2±0.1 and CSA 1.8±1.3%, p<0.05). Neutrophils count was increased in AMI (6.8±0.4 vs C 3.8±0.2 and CSA 3.4±0.3 x103/mL vs, p<0.01). MPO content and circulating neutrophils count were linearly correlated (R2=0.48, p<0.05). AMI patients showed a significant increase of circulating neutrophil-platelet aggregates (13.6±5.5 vs C: 3.0±0.3 vs CSA: 3.7±0.6; P<0.001), of fibrinogen binding to neutrophils (18.4±2.8 vs C: 2.4±0.4 vs CSA: 2.1±0.6; p<0.001) and of expression of the active form of Mac-1 (62.0±6.0 vs C 8±2 vs CSA 13±1; P<0.001). None of these parameters was correlated with Trop I levels (R2=0.46, p=ns). Confocal microscopy showed:
association of complete neutrophil degran-ulation and selective expression of the active form of Mac-1 at the site of interaction with platelets.
polarized distribution of activated Mac-1 and fibrinogen with complete degranu-lation. All activation markers returned to normal after 36 hrs.
Conclusions: The very onset of AMI is associated with an intense, transient neutrophil activation and degranulation, unrelated to coronary atherosclerotic burden or myocardial necrosis. Both cytometric and confocal findings suggest that the neutrophil-platelet interaction is involved in transient neutrophil activation and degranulation of circulating neutrophils in the very early phases of AMI.