Published: Coronary vascular growth matches IGF-1-stimulated cardiac growth in fetal sheep

Our new paper about coronary growth and function in the fetal heart!

What is it about?

The coronary arteries are what supplies oxygen to the working muscle of the heart. We can increase the amount of heart muscle in the fetal sheep by giving it IGF-1. In this study, we asked how the coronary arteries change when we grow the fetal heart with IGF-1. We found that the coronaries grew proportionally to muscle growth, and continued to function normally.

We also looked at what "normal function" means in the fetal coronaries. We found that two signaling molecules were largely responsible for the increased in coronary blood flow when the fetus is challenged by low oxygen: adenosine and nitric oxide.

Why is it important?

Fetal coronary physiology hasn't been explored much experimentally because it's very technically challenging work. A lot of work has been done looking at regulation of cardiomyocytes growth and maturation, but it is important to have coronary flow matched to the heart muscle, otherwise it won't get enough oxygen.

Now we know that if we use IGF-1 to grow bigger hearts in fetuses, their coronaries will grow to support the new muscle. And we know that adenosine and nitric oxide are important for getting oxygen to the fetal heart when it is challenged by low oxygen levels.

Perspective

Given the role that coronary arteries play in adult disease, and the role of development in determining adult disease, it's critically important to address these questions.

It wouldn't be a good research study if it didn't raise more questions to answer, and one question that we're now pondering is what's going on in the hypoxic fetal myocardium when oxygen delivery per work decreases steeply without a reduction in cardiac work.

Read the paper at The FASEB Journal or find it on Pubmed.

Figure 2 from the publication
Figure 2 from the publication. Coronary pressure‐flow relationship example. A pressure‐flow relationship example from an IGF‐1‐treated fetal sheep. At day 0 (127 d gestational age [GA]) and at day 7 (134 dGA, term = 147 dGA) after chronic IGF‐1 treatment, autonomic responses were blocked and vascular occluders were used to transiently increase or decrease coronary driving pressure. Then, a maximally vasodilating dose of adenosine was administered to the coronary circulation, and the pressure manipulations were repeated. The slope of each relationship is the coronary conductance, and the difference between the slopes at a given pressure, on a given day, is the coronary reserve.