When does the Human Heart Transition from Hyperplastic Myocyte Growth to Myocyte Hypertrophy? : Cardiology Discovery

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When does the Human Heart Transition from Hyperplastic Myocyte Growth to Myocyte Hypertrophy?

Gerdes, A Martin

Editor(s): Xu, Tianyu; Fu., Xiaoxia

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Cardiology Discovery 1(3):p 202-203, September 2021. | DOI: 10.1097/CD9.0000000000000028
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At some point after birth, myocyte hyperplasia ceases, and myocyte hypertrophy accounts for the remaining growth of myocytes composing the heart from that point forward. Heart weight increases in proportion to myocyte volume after this transition. In rat heart, this transition occurs abruptly at postnatal day 4.[1] The transition point in humans is unknown and has proven very difficult to identify from a technical standpoint. For instance, even if autopsied hearts were optimally preserved, which is unlikely, it is difficult to definitively distinguish between mitosis in myocytes and non-myocytes in many cases. Additionally, karyokinesis (binucleation/multinucleation) continues as myocytes hypertrophy after cessation of cytokinesis. So, mitosis is not a definitive marker of myocyte proliferation. Identifying the transition point in humans is of scientific interest and potentially helpful in timing surgical procedures necessary to correct congenital heart defects. For instance, timing surgery before the transition may beneficially affect cardiac myocytes in adulthood. With conditions such as hypoplastic left heart syndrome, optimal surgical timing could make a difference in outcomes if surgery could be completed during the myocyte hyperplastic period before the heart has lost the ability to make new myocytes. Theoretically, these hearts may then have a normal complement of left ventricular myocytes upon reaching adulthood.

It recently dawned on me that the human transition point can be calculated using available published information from my laboratory. After demonstrating a precise method to determine cardiac myocyte volume by Coulter Channelyzer analysis of isolated myocytes,[2] we found that mean myocyte volume in adult mammalian hearts is essentially the same.[3] Similar mean myocyte volume was found in adult hearts from humans, rats, guinea pigs, hamsters, cats, dogs, mice, and sheep.[3] Species differences in heart mass are primarily due to differences in myocyte number rather than size. The average myocyte volume in adult mammalian hearts is about 36,000 μm3, with values from males being slightly larger and females slightly smaller due to the effect of body mass differences.[4] Mammalian hearts have approximately 25 million myocytes per gram of ventricular myocardium.[4] During the phase of hyperplastic growth, myocyte volume is ∼1400 μm3. Consequently, myocyte size increases ∼26-fold during postnatal growth and maturation, with a proportional increase in heart mass.[1] The mean heart weight in humans is ∼300 g, and 1/26 of that amount is ∼12 g. Consequently, the transition from myocyte hyperplasia in humans should occur at a heart weight of ∼12 g. This appears to be at about the time of birth.[5] Unfortunately, this suggests that late-term intervention may be necessary for timing during the myocyte hyperplastic phase. Nonetheless, this calculation should provide a reasonable estimation of the transition point in humans.

Over the past few decades, considerable effort has been directed toward stimulating myocyte hyperplasia as a possible means for cardiac repair in adults with heart disease. This has proven to be a very difficult and complicated undertaking with many potential problems. For instance, can this be done without increasing the incidence of cardiac cancers? What's interesting to me is that a given mammalian heart somehow knows how many cell cycles must be undertaken to end up with the correct number of myocytes for a given-sized mammal. A human heart undergoes many more myocyte proliferation cycles than a rat heart to end up with about 7.5 billion myocytes versus 1 million for a rat. How do the myocytes know this, and can we overcome this replication barrier?



Conflicts of interest


Editor note: A Martin Gerdes is an Editorial Board Member of Cardiology Discovery. The article was subject to the journal's standard procedures, with peer review handled independently by this editor and his research groups.


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[2]. Gerdes AM, Moore JA, Hines JM, et al. Regional differences in myocyte size in normal rat heart. Anat Rec 1986;215(4):420–426. doi: 10.1002/ar.1092150414.
[3]. Gerdes AM. Cardiac myocyte remodeling in hypertrophy and progression to failure. J Card Fail 2002;8(6 Suppl):S264–268. doi: 10.1054/jcaf.2002.129280.
[4]. Bai SL, Campbell SE, Moore JA, et al. Influence of age, growth, and sex on cardiac myocyte size and number in rats. Anat Rec 1990;226(2):207–212. doi: 10.1002/ar.1092260210.
[5]. Rasten-Almqvist P, Eksborg S, Rajs J. Heart weight in infants – a comparison between sudden infant death syndrome and other causes of death. Acta Paediatr 2000;89(9):1062–1067. doi: 10.1080/713794581.
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