title: Subchronic preexposure to carbon monoxide modifies heart response to a combined CO + isoproterenol challenge in rats.
abstract: The effect of repeated exposure to carbon monoxide (CO) on the response of middle-age rats to an acute CO exposure combined with a low dose of a sympathomimetic agent was studied. A group of 12 rats (male albino, Wistar, age 9 months) without ECG abnormalities was divided into two subgroups matched for weight, heart rate and ECG: one subgroup was exposed to 500 ppm CO for 6 h/d, 5 d/w, for 6 weeks (peak COHb 31.5%, SD 3.5); the other one (controls) was exposed to fresh air. Two or three days after the last exposure both groups underwent combined challenge with 0.025 mg/kg isoproterenol s.c. and 90 minute exposure to CO in a concentration increasing from 500 to 1500 ppm; ECG was recorded continuously. The hearts were examined morphometrically and histologically. The CO-preexposed subgroup had, as compared to controls: 1) significantly higher blood hemoglobin (by 25%), erythrocyte count (by 28%) and volume (by 6%), and hematocrit (by 33%); 2) the same peak COHb; 3) lower basic heart rate and an earlier decrease after isoproterenol, 4) significantly smaller increase in ECG abnormalities and arrhythmias after isoproterenol and during CO exposure; 5) nonsignificantly higher heart weight indexes; 6) a nonsignificantly lower score of histological abnormalities. The global score of ECG pathology during CO exposure (abnormal pattern or arrhythmia) correlated best (multiple corr. coef. >0.9) with end-exposure free (non CO bound) hemoglobin (negatively) and with mean heart rate during exposure (positively): the lower score in the preexposed subgroup was attributable primarily to the increased hemoglobin. Six-week intermittent CO exposure induced marked compensatory processes (hematological) but only a tendency to adaptational changes in the heart (by gross morphometry), and decreased the ECG response to CO+ isoproterenol challenge at the same COHb.
authors.affiliation: National Institute of Public Health, Prague, Czech Republic. ztravni@szu.cz
authors.forename: Z
authors.initials: Z
authors.lastname: Trávnícková
authors.forename: E
authors.initials: E
authors.lastname: Frantík
authors.forename: K
authors.initials: K
authors.lastname: Blazek
authors.forename: S
authors.initials: S
authors.lastname: Janousek
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D002248:Carbon Monoxide / Q000633:toxicity*; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects*; D004906:Erythrocyte Count / Q000187:drug effects; D004911:Erythrocyte Volume / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006454:Hemoglobins; D002248:Carbon Monoxide; D007545:Isoproterenol