Cardiac remodelling as a result of pre-term birth: implications for future cardiovascular disease.
OBJECTIVE
Pre-term birth affects 10-12% of live births and occurs when the myocardium is still developing; therefore, the final structure of the myocardium could be altered. We hypothesized that, in response to pre-term birth, structural remodelling occurs within the myocardium which enables the immature heart muscle to adapt to the haemodynamic transition at birth but results in persistent alterations in its structure. Our objective was to determine how pre-term birth alters the final structure of the myocardium.


RESULTS
Using sheep, pre-term birth was induced at 0.9 of term; hearts were examined at 9 weeks after term-equivalent age, when cardiomyocyte proliferation and maturation have ceased. In pre-term lambs, we found that cardiomyocytes of both ventricles and the interventricular septum were hypertrophied. Cardiomyocyte maturation in pre-term lambs was altered in that there was a greater proportion of mononucleated, polyploid (4n) cardiomyocytes in both ventricles compared with controls; importantly, induction of polyploidy is associated with irreversible stress-related changes in DNA. We also found a six- to seven-fold increase in collagen deposition, usually accompanied by lymphocytic infiltration.


CONCLUSIONS
We conclude that pre-term birth leads to remodelling of the myocardium that alters its final structure. This may programme for long-term cardiac vulnerability.
Bensley
Jonathan G
JG
Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia.
Stacy
Victoria K
VK
De Matteo
Robert
R
Harding
Richard
R
Black
M Jane
MJ
D000818:Animals; D002318:Cardiovascular Diseases / Q000196:embryology*; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D005260:Female; D006321:Heart / Q000196:embryology*; D007150:Immunohistochemistry; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology; D009929:Organ Size; D011003:Ploidies; D011247:Pregnancy; D047928:Premature Birth; D012756:Sheep; D020257:Ventricular Remodeling
D003094:Collagen