Ultrafine particulate matter exposure augments ischemia reperfusion injury in mice

Abstract

Epidemiological studies have linked ambient particulate matter (PM) levels to an increased incidence of adverse cardiovascular events, yet little is definitively known about the mechanisms underlying these events. To test the hypothesis that ultrafine PM exposure increases ischemia reperfusion (IR) injury, mice were exposed to 100μg of PM (n = 16) or vehicle (n = 14) by tracheal instillation. 24 hr later, the left anterior descending coronary artery (LAD) was ligated for 20 min, flow was restored for 2 hr, and the resulting myocardial infarct (MI) size was measured. PM doubled the size of the MI compared to vehicle control (48 ± 4 vs 23 ± 3 % area at risk (AAR), p < 0.001). No difference was observed in the size of the AAR (33 ± 1vs 31 ± 1 % left ventricle (LV), p = 0.4). PM increased oxidative stress (196 ± 48 vs 111 ± 28 μmol/malondialdehyde/mg LV protein, p = 0.04) and neutrophil density (392 ± 23 vs 270 ± 32 cells/mm2/AAR, p = 0.01) in the myocardium after IR. Blood leukocytes were reduced in the PM compared to vehicle control (2959 ± 216 vs 4298 ± 473 ml/blood, p = 0.02). These results demonstrate that exposure to PM increases oxidative stress in the myocardium and augments injury after IR. This abstract does not necessarily reflect EPA policy. Supported by Philip Morris Foundation #567881.