Coronary Vascular Growth Matches IGF-1-stimulated Cardiac Growth in Fetal Sheep

As loss of contractile function in heart disease could often be mitigated by increased cardiomyocyte number, expansion of cardiomyocyte endowment paired with increased vascular supply is a desirable therapeutic goal. Insulin-like growth factor 1 (IGF-1) administration increases fetal cardiomyocyte proliferation and heart mass, but how fetal IGF-1 treatment affects coronary growth and function is unknown. Near-term fetal sheep underwent surgical instrumentation and were studied from 127 to 134 d gestation (term = 147 d), receiving either IGF-1 LR3 or vehicle. Coronary growth and function were interrogated using pressure-flow relationships, an episode of acute hypoxia with progressive blockade of adenosine receptors and nitric oxide synthase, and by modeling the determinants of coronary flow. The main findings were that coronary conductance was preserved on a per-gram basis following IGF-1 treatment, adenosine and nitric oxide contributed to hypoxia-mediated coronary vasodilation similarly in IGF-1-treated and Control fetuses, and the relationships between coronary flow and blood oxygen contents were similar between groups. We conclude that IGF-1-stimulated fetal myocardial growth is accompanied by appropriate expansion and function of the coronary vasculature. These findings support IGF-1 as a potential strategy to increase cardiac myocyte and coronary vascular endowment at birth.