Electrocardiographic changes induced by diesel exhaust particles (DEP) in guinea pigs

We have previously reported that diesel exhaust particles (DEP) caused a ne gative inotropic effect that was followed by cardiac arrest in the isolated atrial preparation of guinea pigs. The purpose of this study was to examin e the systemic effects of DEP on electrocardiographic (ECG) changes using g uinea-pigs. We found that intravenously administered dimethyl sulfoxide (DM SO) extract of DEP solution induced arrythmias and deaths via complete atri oventricular (AV) block in guinea pigs. The LD of DEP solution was 132.0 +/ - 7.2 mg/kg. The coefficient of variance (CV) of LD measured by the modifie d Hatcher-Magnus method was relatively small (5.5%). Fractions of DEP extra cted by hexane, ethanol or methanol, 4-hydroxyphthalic acid 2-methyl ester, a compound isolated from methanol extract of DEP did not induce significan t ECG changes in guinea pigs. As compared with fresh DEP solution, the DMSO /DEP solution used in the present study induced similar cardiac toxicity af ter being stored in a freezer at 4 degrees C for 3 days. These results sugg est that stable and water-soluble fractions of DEP may be responsible for c ardiotoxicity.