Right ventricular systolic pressure load alters myocyte maturation in fetal sheep

Abstract

The effects of right ventricular (RV) systolic pressure (RVSP) load on fetal myocyte size and maturation were studied. Pulmonary artery (PA) pressure was increased by PA occlusion from mean 47.4 +/- 5.0 (+/-SD) to 71 +/- 13.6 mmHg (P < 0.0001) in eight RVSP-loaded near-term fetal sheep for 10 days. The maximal pressure generated by the RV with acute PA occlusion increased after RVSP load: 78 +/- 7 to 101 +/- 15 mmHg (P < 0.005). RVSP-load hearts were heavier (44.7 +/- 8.4 g) than five nonloaded hearts (31.8 +/- 0.2 g; P < 0.03); heart-to-body weight ratio (10.9 +/- 1.1 and 6.5 +/- 0.9 g/kg, respectively; P < 0.0001). RVSP-RV myocytes were longer (101.3 +/- 10.2 microm) than nonloaded RV myocytes (88.2 +/- 8.1 microm; P < 0. 02) and were more often binucleated (82 +/- 13%) than nonloaded myocytes (63 +/- 7%; P < 0.02). RVSP-loaded myocytes had less myofibrillar volume than did nonloaded hearts (44.1 +/- 4.4% and 56. 1 +/- 2.6%; P < 0.002). We conclude that RV systolic load 1) leads to RV myocyte enlargement, 2) has minor effects on left ventricular myocyte size, and 3) stimulates maturation (increased RV myocyte binucleation). Myocyte volume data suggest that RV systolic loading stimulates both hyperplastic and hypertrophic growth.

Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro

“…It is clear that the last third of ovine gestation is a critical window for the developing myocardium because during that period the heart must gain the complement of cardiomyocytes that will carry it through the stress-laden birth transition. During this period, both mono-and bi-nucleated myocyte populations are sensitive to nutritional, hormonal, and hemodynamic modifications (Barbera et al 2000, Sundgren et al 2003a, Giraud et al 2006.…”

“…In humans and large mammals, the heart grows entirely by cardiomyocyte proliferation during the first half of gestation (Smolich et al 1989, Austin et al 1995, Mayhew et al 1997. Thereafter, cardiomyocytes undergo terminal differentiation and binucleation at an increasing rate (Barbera et al 2000, Burrell et al 2003, so that some 80% of cardiomyocytes are binucleated at the time of birth. Evidence suggests that binucleated cardiomyocytes cannot divide (Clubb & Bishop 1984), these cells contribute to increased heart weight only by cellular hypertrophy (increased cell size), but not by hyperplasia.…”

Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts

“…Concomitant with the development of cardiac hypertrophy in the adult are qualitative and quantitative changes in gene expression, including upregulation of the so-called fetal cardiac genes, including ␤-myosin heavy chain, ␣-actin, and atrial natriuretic factor, and a reversion to fetal metabolic pathways for energy production (1,32,33,43). In the fetal heart, however, the molecular triggers for increasing ventricular mass in response to increased load are poorly understood and may be quite different from those in the adult, particularly given the ability of the fetal heart to increase mass by both hypertrophy and hyperplasia (2,25,29).In response to increased ventricular load and wall stress, coronary vasodilation occurs to meet the increased metabolic needs of the myocardium. Despite maintaining a greater resting myocardial blood flow than the adult, the late-gestation fetus is able to increase myocardial flow during increases in ventricular pressure, suggesting myocardial blood flow is closely linked to metabolic needs even early in development (8,29).…”

The effect of feto-maternal size and childhood growth on left ventricular mass and arterial stiffness in Afro-Caribbean children

“…2,[39][40][41][42][43] Intrauterine undernutrition may cause hypercortisolaemia, which can cause accelerated cardiac ontogeny, tipping the balance to cardiac fibrosis, and in turn giving rise to cardiac dysfunction. 39 In addition, early pressure loading of cardiac myocytes may lead to fewer but larger myocytes.…”

“…39 In addition, early pressure loading of cardiac myocytes may lead to fewer but larger myocytes. 40 Large artery elasticity is dependent on elastin, which is laid down in utero and during infancy. Intrauterine undernutrition causes shunting of blood flow from the trunk to the brain, and reduces elastin deposition in the large arteries of the trunk and legs, making these vessels less compliant and facilitating the development of hypertension in adult life.…”