Exposure of neonatal rats to carbon monoxide alters cardiac adaptation to aortic constriction

Abstract

We tested the hypothesis that a 32-day exposure of newborn rats to 500 ppm carbon monoxide (CO) would alter the adaptive response of the heart to aortic constriction in adulthood. At 110 days of age aortic constriction or sham operations were performed, and hearts were studied 28 days later. Aortic constriction increased left ventricular (LV) mass by 40% over the control value of 611 +/- 27 mg; this adaptive response was not altered by CO exposure. Aortic constriction and CO exposure increased right ventricular (RV) mass by 10 and 11%, respectively, over the control value of 185 +/- 10 mg. The effects of both experimental procedures on RV mass were additive (23%). Peak LV pressure development (dP/dtmax) in vitro increased 29% after aortic constriction in the nonexposed rats. CO exposure blunted the increase in peak LV systolic pressure due to aortic constriction. Maximum positive and negative dP/dtmax decreased by 19% after aortic constriction and were unaffected by CO exposure. The percentage of alpha-myosin heavy chain (MHC) in the ventricles was 94 +/- 2% in the control group and was decreased to 81 +/- 3% by aortic constriction. In contrast, the percentage of alpha-MHC was 87 +/- 2% for CO-exposed rats and was not significantly altered after aortic constriction. In vitro coronary flow was increased 18% in hearts of adult rats exposed to CO as neonates. Exposure of neonatal rats to CO induced chronic adaptations in the myocardium, some of which became evident in adulthood only when hearts were challenged by aortic constriction.