The effects of anaemia as a programming agent in the fetal heart

Abstract

The intrauterine environment plays a powerful role in determining the life-long risk of cardiovascular disease. A number of stressors are well known to affect the development of the cardiovascular system in utero including over/under maternal nutrition, excess glucocorticoid and chronic hypoxia. Chronic fetal anaemia in sheep is a complex stressor that alters cardiac loading conditions, causes hypoxic stress and stimulates large changes in flow to specific tissues, including large increases in resting coronary blood flow and conductance. Decreased viscosity can account for approximately half of the increased flow. It appears that immature hearts are 'plastic' in that increases in coronary conductance with fetal anaemia persist into adulthood even if the anaemia is corrected before birth. These large changes in conductance are possible only through extensive remodelling of the coronary tree. Adult hearts that were once anaemic in utero are more resistant to hypoxic stress as adults but it is not known whether such an adaptation would be deleterious in later life. These studies indicate the need for investigation into the basic mechanisms of coronary tree remodelling in the immature myocardium. New information on these mechanisms is likely to lead to better prevention of and therapies for adult-onset coronary disease.

Figure 1. Regional blood flow after 7 days of anaemia

Regional blood flow in chronically anaemic and control fetal sheep at near term as determined by microspheres. Data taken from Davis & Hohimer (1991).

Figure 2. Coronary pressure–flow relationships

Coronary pressure–flow relationships in a singleton fetus before and after anaemia induced over 1 week. Resting coronary blood flow shows normal autoregulation. Resting flow when anaemic is at the maximal flow in response to adenosine 1 week earlier. Reproduced with permission from Davis et al. (1999).

Figure 3. Maximal coronary conductance in response to adenosine

Maximal left ventricular coronary conductance measured in ovine fetuses that were anaemic as compared to controls, in ovine fetuses infused with adenosine into the coronary circulation to increase flow without altering oxygen content as compared to controls, and in adult sheep that were anaemic in utero only as compared to control twin siblings. Data from Davis et al. (1999) and Wothe et al. (2002); reproduced from Davis et al. (2003).

Figure 4. Coronary reserve

Coronary reserve ovine fetuses that were anaemic as compared to controls, in ovine fetuses infused with adenosine into the coronary circulation to increase flow without altering oxygen content as compared to controls, and in adult sheep that were anaemic in utero only as compared to control twin siblings. Data from Davis et al. (1999) and Wothe et al. (2002); reproduced from Davis et al. (2003).