Birth is Associated with Reduced Coronary Capacity in Sheep

Abstract

The transition from fetal to neonatal life is among the most universal and rapid changes in physiology encountered in mammalian life. In this study, we sought to directly characterize the effects of birth on the function and capacity of the coronary vasculature in a large animal model of cardiac development. We hypothesized that significant increases in coronary reserve and oxygen delivery would accompany the increased demands placed on the myocardium by the challenges of postnatal life, including dramatic increases in pulmonary blood flow, left ventricular preload, and cardiac output. Near term fetuses (N = 7), and term-born lambs (N = 5) of mixed western breed ewes were instrumented with catheters (aortic arch, right atrium, left atrium), inflatable occluders (inferior vena cava, postductal thoracic aorta), and a Transonic flow probe (left circumflex coronary artery). Studies (unanesthetized) were carried out at least 3 days later (135-136 days gestation (term = 147 days)) or 5-6 d postnatal. Pressure-flow relationships were determined at rest or at maximal adenosine-induced hyperemia. The mass of myocardium served by the artery from which flow was measured was determined by postmortem Evan's Blue perfusion; all reported flow values are normalized to this mass. Cardiac work is the double product of driving (aortic minus right atrial) pressure. We define coronary conductance as the slope of the pressure-flow relationships, and coronary flow reserve as the fold change in coronary flow between resting and hyperemic conductance. Differences between fetuses and neonates were assessed by the Mann-Whitney U-test and considered significant when p < 0.05. Basal cardiac work was significantly greater after birth, as heart rate and driving pressure were 1.3 and 1.6-fold greater in neonate than fetus (p = 0.009, p = 0.003, respectively). Resting coronary flow was 1.8-fold lower in the neonate than the fetus (p = 0.048). Despite a 1.6-fold increase in arterial blood oxygen content (p = 0.006), baseline oxygen delivery per work in the neonate was less than half that in the fetus (p = 0.005; Figure 1A). Pressure-flow relationships (Figure 1B) likewise showed a reduction in coronary conductance from fetus to neonate both at rest (2.3-fold, p = 0.073) and with adenosine hyperemia (2-fold, p = 0.048). Estimated hyperemic coronary flow at resting daily pressures were decreased by 1.6-fold in the neonate (p = 0.03). Coronary flow reserve was similar between fetuses and lambs (p = 1; Figure 1C). Despite the increased cardiac demands of postnatal life, these results suggest that there is not an increase in coronary reserve or capacity following birth. Rather, we find evidence of lower resting and maximal coronary flow in the postnatal period such that flow reserve is maintained. This evidence of an actively regulated decrease in coronary capacity shows the functional consequence of a known reduction in capillary to fiber ratio occurring in the myocardium between birth and maturity. Future studies of myocardial perfusion focusing on microvascular structure and function are therefore warranted.