Cardiomegaly due to myocyte hyperplasia in perinatal rats exposed to 200 ppm carbon monoxide

Exposure to carbon monoxide (CO) during the fetal and neonatal period was used to evaluate cardiac ventricular regional weight and myocyte growth response to an increased hemodynamic load. Date-mated Sprague-Dawley rats inhaled 200 ppm CO from day 7 of pregnancy until parturition; another group of pregnant rats inhaled room air. At birth, pups from these two groups were subdivided into four groups: (1) control group (AIR/AIR), that was maintained in room air in utero and post-partum; (2) AIR/CO group, which received CO only after birth; (3) CO/CO group, which received CO exposure in utero and post-partum; and (4) CO/AIR group, which received CO exposure in utero but was maintained in room air post-partum. Rats were removed from litters at selected intervals from birth to 28 days of age and used to determine regional ventricular weights and ventricular dry weights, and to obtain isolated myocyte preparations for measurement of cell size characteristics and allow calculation of cell numbers. Compared with AIR raised control animals, right ventricular weight was increased in animals exposed to CO during the fetal period. Post-natal CO exposure caused an increase in left ventricular weight. Heart weight to body weight ratio of animals exposed to CO post-natally only (AIR/CO) gradually increased to reach that of the CO/CO group by 12 days of age, while animals exposed to AIR post-natally following fetal CO exposure gradually decreased their heart weight to body weight ratio toward that of the control animals by 28 days of age. Binucleated cells first appeared at 4 days of age in all groups. Myocyte volume was similar in both groups at birth and increased from six through 28 days of age. Left ventricle plus septum and right ventricle cell volumes of the CO/CO group were smaller than the controls at 28 days of age in spite of heavier wet and dry weights in the CO-exposed rats. At birth, the CO-exposed animals had more myocytes in the RV compared to AIR-exposed controls. Carbon monoxide exposure after birth resulted in left ventricular myocyte hyperplasia. The results of this study indicate that increased hemodynamic load due to CO exposure during the fetal period results in cardiomegaly because of increased myocyte hyperplasia. This cellular response is sustained through the early neonatal period in animals exposed to CO both in utero and post-partum.