Abstract P312: Tracheal Instillation of Diesel Exhaust Particles Exacerbates Myocardial Ischaemia and Reperfusion Injury in Rats
Episodes of increased air pollution are associated with higher cardiovascular mortality. The adverse effects of air pollution have been attributed to particulate matter, especially ultrafine particles. This study addresses the hypothesis that ultrafine diesel exhaust particles (DEP) exacerbate myocardial ischaemia reperfusion (I/R) injury secondary to induction of a systemic inflammatory response. Wistar rats (n=5–6/group) received DEP (0.5 mg) or saline vehicle by intratracheal instillation. 6h later I/R was induced either in vivo or ex vivo in isolated buffer perfused hearts. Lung inflammation was confirmed 6h after DEP instillation by increased levels of neutrophils, total protein and IL-6 in bronchoalveolar lavage fluid. However, there was no evidence for systemic inflammation as assessed by plasma cytokine levels (IL-6, TNF-α, and CRP) or by neutrophil priming (CD11b expression) or activation (CD62L expression). In vivo, systolic blood pressure was significantly higher in DEP-instilled rats (129 ± 7 mmHg) than in saline controls (92 ± 3 mmHg, P<0.01), consistent with increased autonomic activation. Arrhythmias occurred intermittently after induction of ischaemia (in total 8.2±1.2 s in the saline group) and were more prevalent in DEP-instilled rats (32.9±5.0s, P<0.001). Fatal arrhythmias occurred in 60% of rats receiving DEP but not at all in saline controls. Following reperfusion, infarct size (extent of triphenyltetrazolium chloride staining) was significantly increased after DEP (34.7 ± 1.2% left ventricle) vs saline-instilled (10.3 ± 1.2%, P<0.001). Infarct size was similarly potentiated in hearts isolated from DEP instilled rats and perfused ex-vivo. Histological examination confirmed the absence of inflammatory infiltrate in hearts prior to I/R. Prior exposure to pollution in vivo thus renders the heart more vulnerable to I/R injury, either in situ in the body or ex vivo when the heart is isolated from systemic mediators and cells. Systemic inflammation does not appear to be necessary for this ‘priming’ effect of DEP. The role of autonomic activation in promoting cardiac arrythmia in vivo after DEP instillation and in determining the ability of the heart to withstand subsequent I/R injury merits further investigation.
- © 2011 by American Heart Association, Inc.