A CRITICAL EARLY POSTNATAL-PERIOD FOR THE STRESS-INDUCED ALTERATION OF HEART DEVELOPMENT - PERSISTENT CARDIOMEGALY AND ALTERED DNA CONTENT

Neonatal carbon monoxide exposure produces persistent heart changes; however, the importance of the duration of exposure and the immediacy of the exposure following birth are unclear. Newborn rats inhaled 500 ppm CO continuously for 0-10 days ("10 days"), 0-20 days ("20 days"), 0-32 days ("32 days"), and 16-32 days ("16-32 days") after birth; a fifth group was not exposed to CO ("AIR"). Maximal initial RV cardiomegaly was present in the 10-day group and continued nearly at that level in the 20- and 32-day groups. Although significant persistent RV cardiomegaly was present in the 10-day group as 154-160 day-old adults, persistent RV cardiomegaly was maximal in the 20- and 32-day groups. While moderate initial RV cardiomegaly developed in the 16-32-day group, no significant persistent RV cardiomegaly resulted. The differences in heart mass were not due to changes in the ratio of wet weight: dry weight. The initial RV cardiomegaly which was present in the 10- and 20-day groups occurred in the absence of elevated hematocrit, although hematocrit had increased by 32 days of age in both the 32- and 16-32-day groups. DNA content was elevated in all four CO-exposed groups immediately post-CO exposure relative to the same age AIR groups, particularly in the RV (30-51%). In adulthood, ventricular DNA content was significantly elevated only in the rats exposed to CO from birth (RV, 12-30%), not in those in which CO exposure began 16 days postbirth (9%). There were no significant differences in DNA concentration between the five groups for given heart regions. The results extend previous studies which demonstrate the persistent alteration of heart development, by showing that the window of opportunity for this process extends from birth until only approximately 2-weeks of age. This finding is consistent with other studies showing cessation of myocyte mitosis at this time.