| An adverse environmental experience of the growing fetus may lead to permanent changes in the structure and function of organs that may predispose the individual to chronic diseases in later life, however nothing is known about the occurrence and the mechanisms of heart failure. A rat model was employed in which pregnant dams were fed diets containing either 180 (normal) or 90 g (low) caesin/kg diet for 2 wks before mating and throughout pregnancy. The ejection fraction (EF) of the pups exposed to the low protein (LP) diet was severely depressed in the first 2 weeks of life, with the peak trough at 7 days, followed by a recovery and normalization of the EF of the offspring up to 40 weeks of age. The left ventricular (LV) internal diameters were increased between 24 hrs and 12 weeks of age in the LP exposed group. Although, between 3 days and 2 weeks of age the LV wall of the hearts of the LP group were thinner, a progressive increase in the LV wall thickness was seen. It is believed that loss of cardiac contractile performance may be due to the reduction in the development of functional myocytes or due to apoptosis in low protein exposed group. Depressed expression of myocyte enhancer factors (MEF2)-C and -D in early life and increased expression in later life in LP exposed group, showed that these changes could be related to early impaired cardiac development and function and later compensatory recovery. Early increases in the atrial natriuretic factor and phospholipase C isozymes mRNA levels occurred in the LP group. At 40 weeks of age although the EF was normal, a 2-fold elevation in the LV end diastolic pressure, a reduced mean arterial pressure and cardiac output as well as decreased maximum rate of pressure development (+dP/d tmax and maximum rate of pressure decay (-dP/d tmax) were observed. The results of this study show that exposure of the developing fetus to maternal low protein induces cardiac dysfunction in offspring in later life. |
