Right ventricular remodeling in response to volume overload in fetal sheep

Tara Karamlou, George Giraud, Donogh McKeogh, Sonnet Jonker, Irving Shen, Ross M. Ungerleider, Kent Thornburg

Research output: Contribution to journalArticle

Abstract

The fetal myocardium is known to be sensitive to hemodynamic load, responding to systolic overload with cellular hypertrophy, proliferation, and accelerated maturation. However, the fetal cardiac growth response to primary volume overload is unknown. We hypothesized that increased venous return would stimulate fetal cardiomyocyte proliferation and terminal differentiation, particularly in the right ventricle (RV). Vascular catheters and pulmonary artery flow probes were implanted in 16 late-gestation fetal sheep: a right carotid artery-jugular vein (AV) fistula was surgically created in nine fetuses, and sham operations were performed on seven fetuses. Instrumented fetuses were studied for 1 wk before hearts were dissected for component analysis or cardiomyocyte dispersion for cellular measurements. Within 1 day of AV fistula creation, RV output was 20% higher in experimental than sham fetuses ( P < 0.0001). Circulating atrial natriuretic peptide levels were elevated fivefold in fetuses with an AV fistula ( P < 0.002). On the terminal day, RV-to-body weight ratios were 35% higher in the AV fistula group ( P < 0.05). Both left ventricular and RV cardiomyocytes grew longer in fetuses with an AV fistula ( P < 0.02). Cell cycle activity was depressed by >50% [significant in left ventricle ( P < 0.02), but not RV ( P < 0.054)]. Rates of terminal differentiation were unchanged. Based on these studies, we speculate that atrial natriuretic peptide suppressed fetal cardiomyocyte cell cycle activity. Unlike systolic overload, fetal diastolic load appears to drive myocyte enlargement, but not cardiomyocyte proliferation or maturation. These changes could predispose to RV dysfunction later in life. NEW & NOTEWORTHY Adaptation of the fetal heart to changes in cardiac load allows the fetus to maintain adequate blood flow to its systemic and placental circulations, which is necessary for the well-being of the fetus. Addition of arterial-venous fistula flow to existing venous return increased right ventricular stroke volume and output. The fetal heart compensated by cardiomyocyte elongation without accelerated cellular maturation, while cardiomyocyte proliferation decreased. Even transient volume overload in utero alters myocardial structure and cardiomyocyte endowment.

Original languageEnglish (US)
Pages (from-to)H985-H991
JournalAmerican journal of physiology. Heart and circulatory physiology
Volume316
Issue number5
DOIs
StatePublished - May 1 2019

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Ventricular Remodeling
Cardiac Myocytes
Sheep
Fetus
Heart Ventricles
Fistula
Fetal Heart
Jugular Veins
Placental Circulation
Vascular Access Devices
Atrial Natriuretic Factor
Financial Management
Fetal Development
Carotid Arteries
Stroke Volume
Muscle Cells
Hypertrophy
Pulmonary Artery
Myocardium
Cell Cycle

Keywords

  • atrial natriuretic peptide
  • cardiomyocyte
  • fetus
  • right ventricle
  • volume overload

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Right ventricular remodeling in response to volume overload in fetal sheep. / Karamlou, Tara; Giraud, George; McKeogh, Donogh; Jonker, Sonnet; Shen, Irving; Ungerleider, Ross M.; Thornburg, Kent.

In: American journal of physiology. Heart and circulatory physiology, Vol. 316, No. 5, 01.05.2019, p. H985-H991.

Research output: Contribution to journalArticle

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