Left and right ventricular myocardial morphometry in fetal, neonatal, and adult sheep

This study has examined left (LV) and right ventricular (RV) myocardial morphometry in perfusion-fixed hearts of late-gestation sheep fetuses, neonatal lambs, and adult sheep. During development, myocyte size, intercapillary distance, and myocyte myofibrillar and mitochondrial volume densities increased, whereas capillary density, the myocyte-to-capillary ratio, and the myocyte matrix volume density decreased. RV myocytes were larger than LV myocytes in cross section in fetuses and 4-day-old lambs. LV and RV myocytes were of similar size in 7-day-old lambs. LV and RV myocytes were of larger in older lambs and adult sheep. Differences between LV and RV myocyte volume densities of myofibrils, mitochondria, and matrix were also observed in fetuses and young lambs. As well, variation in capillary size and density was apparent between ventricles in the fetal and neonatal periods. We conclude that, in the sheep heart, 1) LV and RV morphometric differences exist during fetal and postnatal development, 2) fetal LV and RV myocardial morphometry is consistent with an RV dominance in utero, 3) rapid growth of LV and RV myocytes occurs in the perinatal period, and 4) the relative size of LV and RV myocytes does not reflect a postnatal LV dominance until between 1 and 4 wk after birth.

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Sympathectomy stimulates capillary but not precapillary growth in hypertrophic hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.5.h1515 ◽

1991 ◽

Vol 260 (5) ◽

pp. H1515-H1521

Author(s):

R. J. Torry ◽

P. M. Connell ◽

D. M. O'Brien ◽

W. M. Chilian ◽

R. J. Tomanek

Keyword(s):

Pressure Overload ◽

Sympathetic Nerves ◽

Capillary Density ◽

Volume Density ◽

Left Ventricular ◽

Coronary Vasodilation ◽

Cross Sectional ◽

Vascular Growth ◽

Capillary Growth ◽

Intercapillary Distance

Sympathetic nerves are known to influence vascular growth, but their role in coronary vascular adaptations to pressure-overload left ventricular (LV) hypertrophy is unknown. Accordingly, regional sympathectomy (SYMX) was produced by painting a ring of phenol on the posterior third of the LV in seven renal hypertensive (Page: 1 kidney, 1 wrap) and seven normotensive (sham: 1 kidney, no wrap) rabbits. Two months later, maximal myocardial blood flow (MBF) following dipyridamole-induced coronary vasodilation was determined with microspheres in the intact anterior and the sympathectomized posterior regions of conscious rabbits. Histomorphometric methods were then utilized to evaluate capillary density (CD), intercapillary distance (ICD), and volume density (VD) of subepicardial and endocardial samples of each region of perfused-fixed hearts. The Page procedure significantly increased systolic blood pressure (+29%) and LV wt/body wt (+20%) above sham rabbits. In both sham and Page groups, MBF was not significantly different between intact and sympathectomized regions within either group. SYMX did not significantly alter CD, ICD, or VD between regions in the sham animals. In contrast, SYMX significantly increased CD (+30%) and VD (+26%) and decreased ICD (-21%) in the subendocardial region of Page animals. Regional SYMX did not alter myocyte cross-sectional area in Page animals. We conclude that SYMX neither 1) significantly increases resistance vessel cross-sectional lumen area in either normal or hypertrophic hearts, nor 2) significantly influences capillary growth in normal hearts, but SYMX does 3) promote capillary growth in hearts undergoing hypertrophy in response to hypertension.

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Ultrastructure of Aerobic Muscle in Antarctic Fishes may Contribute to Maintenance Of Diffusive Fluxes

Journal of Experimental Biology ◽

10.1242/jeb.150.1.205 ◽

1990 ◽

Vol 150 (1) ◽

pp. 205-220 ◽

Cited By ~ 7

Author(s):

RICHARD L. LONDRAVILLE ◽

BRUCE D. SIDELL

Keyword(s):

Muscle Metabolism ◽

Antarctic Fish ◽

Oxygen Demand ◽

Capillary Density ◽

Volume Density ◽

Active Species ◽

Published Data ◽

Diffusion Distance ◽

Capillary Length ◽

Diffusive Fluxes

Quantitative ultrastructural analyses were performed on red (oxidative) and white (glycolytic) skeletal muscles from two species of antarctic fish to identify features of subcellular structure that may be related to muscle metabolism at cold body temperature. Trematomus newnesi (Boulenger) is an active pelagic species and Notothenia gibberifrons (Lönnberg) is a sluggish bottom-dweller. White fibres of both species are poorly vascularized [capillary density, NA(c,f), for T. newnesi 73.9±11.3mm−2; for N. gibberifrons is 76.0±14.1mm−2], and have low percentages of cell volume occupied by mitochondria [volume density, Vv(mit,f), for T. newnesi is 0.014±0.005; for N. gibberifrons is 0.006±0.003]. Ultrastructure of oxidative fibres in both species resembles that of cold-acclimated temperate-zone fishes. Mitochondrial volume densities of red fibres reflect differences in ecotype between species [Vv(mit,f) for T. newnesi is 0.348±0.012; for N. gibberifrons is 0.249±0.007]. The less clustered array of mitochondria in oxidative fibres of T. newnesi compared with N. gibberifrons may support an equivalent flux of aqueous metabolites between mitochondrial and cytoplasmic compartments, despite a greater mean intracellular diffusion distance (τh) between these compartments in T. newnesi than in N. gibberifrons (τh=1.05±0.07μm and 0.77±0.06μm, respectively). Although Vv(mit.)) is higher in red fibres of the active species, capillary supply is less extensive [capillary length density, Jv(c,f), for T. newnesi is 481.3±49.0mm mm−3; N. gibberifrons is 696.3±33.7mm mm−3] and the maximal diffusion-distance for oxygen is greater in T. newnesi than in N. gibberifrons (Krogh's radius, R=26.3±1.64μm and 21.5±0.51μm, respectively). A mismatch appears to exist between oxygen supply [Jv(c,f)] and oxygen demand [Vv(mit,f)] in T. newnesi red fibres in view of published data for other fishes. The twofold higher volume density of lipid [Vv(lip,f)] in T. newnesi compared with N. gibberifrons may resolve this paradox [Vv(lip,f) is 0.026±0.002 and 0.012±0.004, respectively]. Because oxygen is at least four times more soluble in lipid than in aqueous cytoplasm, lipid may enhance oxygen flux through oxidative muscle and play a role similar to myoglobin in these myoglobin-poor fishes.

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Myocyte/capillary mismatch in the heart of uremic patients.

Journal of the American Society of Nephrology ◽

10.1681/asn.v961018 ◽

1998 ◽

Vol 9 (6) ◽

pp. 1018-1022 ◽

Cited By ~ 3

Author(s):

K Amann ◽

M Breitbach ◽

E Ritz ◽

G Mall

Keyword(s):

Essential Hypertension ◽

Capillary Density ◽

Volume Density ◽

Left Ventricular ◽

Interstitial Tissue ◽

Pump Failure ◽

Capillary Supply ◽

Uremic Patients ◽

Sampling Procedures ◽

Normotensive Control

Experiments indicate that capillary density is reduced in the hypertrophied left ventricle of rats with subtotal nephrectomy compared to control rats with similar BP and left ventricular hypertrophy, suggesting that in uremia, hypertrophying cardiomyocytes outgrow their capillary supply. No information on myocardial capillary supply in humans is currently available. The hearts of nine dialyzed patients, nine patients with essential hypertension, and 10 normotensive control subjects at postmortem were obtained. Subjects with stenosing coronary lesions and left ventricular pump failure were excluded. Special sampling procedures were used to exclude stereologic artefacts. Capillaries were specifically stained with ulex lectin and analyzed by stereologic techniques. Length density of myocardial capillaries (Lv; mm/mm3) was significantly (P < 0.001) lower in dialyzed patients (1483 +/- 238) than in patients with essential hypertension (1872 +/- 243) or in normotensive control patients (2898 +/- 456). In parallel, myocyte diameter and volume density of myocardial interstitial tissue were significantly (P < 0.001) increased in uremic patients compared to patients with essential hypertension and control patients, respectively. Diminished left ventricular capillary supply in renal failure must increase critical oxygen diffusion distance in the myocardium, thus exposing cardiomyocytes to the risk of hypoxia. It is unknown whether such reduced ischemia tolerance can be reversed by increasing oxygen supply (e.g., by reversing anemia).

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Ovine bronchial-derived relaxing factor: changes with development and hyperoxic ventilation

Journal of Applied Physiology ◽

10.1152/japplphysiol.01382.2005 ◽

2006 ◽

Vol 101 (1) ◽

pp. 135-139 ◽

Cited By ~ 3

Author(s):

Satyan Lakshminrusimha ◽

Frederick C. Morin ◽

Robin H. Steinhorn ◽

Sylvia F. Gugino ◽

Rita M. Ryan ◽

...

Keyword(s):

Pulmonary Arteries ◽

Late Gestation ◽

Fetal Life ◽

Developmentally Regulated ◽

Relaxing Factor ◽

Fetal Rat ◽

The Difference ◽

Neonatal Lambs ◽

Synthase Inhibitor ◽

Hyperoxic Ventilation

Recent studies suggest that a bronchial-derived relaxing factor (BrDRF) decreases the contractility of newborn, but not fetal, rat pulmonary arteries (PAs) by a nitric oxide (NO)-mediated mechanism. We studied the effect of an adjacent bronchus on PA contractility to norepinephrine (NE) in late-gestation fetal ( n = 7), neonatal (1 day old, n = 9), ventilated neonatal (24-h ventilation from birth with 100% oxygen, n = 9), and adult sheep ( n = 6) in the presence and absence of the NO synthase inhibitor Nω-nitro-l-arginine (l-NNA). The sheep were anesthetized and killed, and fifth-generation PA rings with and without an attached adjacent bronchus (PA+Br) were contracted in standard tissue baths with NE (10−8–10−6 M). NE contractions were expressed as fraction of KCl (118 mM) contraction and as grams of contraction force. NE contractions were significantly diminished by the presence of an attached bronchus in the neonatal and ventilated neonatal and adult, but not fetal, lambs. Hyperoxic ventilation markedly increased NE contractions in PA and PA+Br. l-NNA significantly enhanced NE contractions in PA+Br in postnatal but not in fetal lambs. Pretreatment with l-NNA abolished the difference between NE contractions in PA and PA+Br in neonatal but not in hyperoxic ventilated neonatal lambs. We conclude that there is a BrDRF that is developmentally regulated and has vascular activity postnatally but not during fetal life. The effect of BrDRF is predominantly mediated by NO in air-breathing neonatal lambs but may involve a second non-NO mediator following hyperoxic ventilation. We speculate that BrDRF may have an important role in postnatal changes in pulmonary arterial reactivity.

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Ontogeny of fetal hepatic and placental growth and metabolism in sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.263.3.r619 ◽

1992 ◽

Vol 263 (3) ◽

pp. R619-R623

Author(s):

I. Vatnick ◽

A. W. Bell

Keyword(s):

Oxygen Consumption ◽

Fetal Liver ◽

Relative Size ◽

Relative Weight ◽

Dry Weight ◽

Maximum Growth ◽

Late Gestation ◽

Progressive Decline ◽

Highly Correlated

Ontogeny of fetal hepatic and placental growth and in vitro oxygen consumption (VO2) was investigated in fetal lambs at 75, 100, and 136 days postconception. Fetal hepatic relative weight and placental absolute and relative weights declined during this period. Oxygen consumption per gram dry weight of fetal liver and maternal placenta declined between mid and late gestation while fetal placental VO2 was unchanged. Estimated VO2 of the whole placenta did not change while the estimated total hepatic VO2 increased more than threefold between 75 and 136 days. Total hepatic VO2 was highly correlated with total placental VO2 at 136 days (r = 0.84). The results suggest that the placenta reaches its maximum growth and metabolic capacity before 100 days and possibly at or before midgestation. Changes in hepatic weight-specific total VO2, in addition to the declining relative size of the fetal liver, must contribute to the progressive decline in metabolic rate of the whole fetus during the second half of pregnancy. Correlations between placental and fetal liver weights and metabolic rates suggest the possibility of placental regulation of fetal hepatic growth and metabolism.

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Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00342.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. R575-R579 ◽

Cited By ~ 70

Author(s):

Marina Korotkova ◽

Britt G. Gabrielsson ◽

Agneta Holmäng ◽

Britt-Marie Larsson ◽

Lars Å. Hanson ◽

...

Keyword(s):

Fatty Acids ◽

Linseed Oil ◽

Maternal Diet ◽

Perinatal Period ◽

Late Gestation ◽

Male Rats ◽

Long Term Effects ◽

Adult Rats ◽

Serum Leptin

Epidemiological studies in humans have shown that perinatal nutrition affects health later in life. We have previously shown that the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) in the maternal diet affects serum leptin levels and growth of the suckling pups. The aim of the present study was to investigate the long-term effects of various ratios of the dietary n-6 and n-3 PUFA during the perinatal period on serum leptin, insulin, and triacylglycerol, as well as body growth in the adult offspring. During late gestation and throughout lactation, rats were fed an isocaloric diet containing 7 wt% fat, either as linseed oil (n-3 diet), soybean oil (n-6/n-3 diet), or sunflower oil (n-6 diet). At 3 wk of age, the n-6/n-3 PUFA ratios in the serum phospholipids of the offspring were 2.5, 8.3, and 17.5, respectively. After weaning, all pups were given a standard chow. At the 28th postnatal wk, mean body weight and fasting insulin levels were significantly increased in the rats fed the n-6/n-3 diet perinatally compared with the other groups. The systolic blood pressure and serum triacylglycerol levels were only increased in adult male rats of the same group. These data suggest that the balance between n-6 and n-3 PUFA during perinatal development affects several metabolic parameters in adulthood, especially in the male animals.

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Shifts in ovine cardiopulmonary microRNA expression in late gestation and the perinatal period

PLoS ONE ◽

10.1371/journal.pone.0204038 ◽

2018 ◽

Vol 13 (9) ◽

pp. e0204038 ◽

Cited By ~ 1

Author(s):

Ramona H. Krauss ◽

Belinda Phipson ◽

Alicia Oshlack ◽

Nikita Prasad-Gupta ◽

Michael M. Cheung ◽

...

Keyword(s):

Perinatal Period ◽

Microrna Expression ◽

Late Gestation

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Contractile and Ca2+-handling properties of the right ventricular papillary muscle in the late-gestation sheep fetus

Journal of Applied Physiology ◽

10.1152/japplphysiol.00214.2006 ◽

2006 ◽

Vol 101 (3) ◽

pp. 728-733 ◽

Cited By ~ 7

Author(s):

T. N. Spencer ◽

K. J. Botting ◽

J. L. Morrison ◽

G. S. Posterino

Keyword(s):

Right Ventricular ◽

Papillary Muscle ◽

Late Gestation ◽

Postnatal Life ◽

Excitation Contraction Coupling ◽

Contraction Coupling ◽

Force Development ◽

Uptake Rates ◽

Significant Difference ◽

The Right

The force-generating capacity of cardiomyocytes rapidly changes during gestation and early postnatal life coinciding with a transition in cardiomyocyte nucleation in both mice and rats. Changes in nucleation, in turn, appear to coincide with important changes in the excitation-contraction coupling architecture. However, it is not clear whether similar changes are observed in other mammals in which this transition occurs prenatally, such as sheep. Using small (70–300 μM diameter) chemically skinned cardiomyocyte bundles from the right ventricular papillary muscle of sheep fetuses at 126–132 and 137–140 days (d) gestational age (GA), we aimed to examine whether changes in cardiomyocyte nucleation during late gestation coincided with developmental changes in excitation-contraction coupling parameters (e.g., Ca2+ uptake, Ca2+ release, and force development). All experiments were conducted at room temperature (23 ± 1°C). We found that the proportion of mononucleate cardiomyocytes decreased significantly with GA (126–132d, 45.7 ± 4.7%, n = 7; 137–140d, 32.8 ± 1.6%, n = 6; P < 0.05). When we then examined force development between the two groups, there was no significant difference in either the maximal Ca2+-activated force (6.73 ± 1.54 mN/mm2, n = 14 vs. 6.55 ± 1.25 mN/mm2, n = 7, respectively) or the Ca2+ sensitivity of the contractile apparatus (pCa at 50% maximum Ca2+-activated force: 126–132d, 6.17 ± 0.06, n = 14; 137–140d, 6.24 ± 0.08, n = 7). However, sarcoplasmic reticulum (SR) Ca2+ uptake rates (but not Ca2+ release) increased with GA ( P < 0.05). These data reveal that during late gestation in sheep when there is a major transition in cardiomyocyte nucleation, SR Ca2+ uptake rates increase, which would influence total SR Ca2+ content and force production.

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Stimulation of gastric proteases in the neonatal pig by a rise in adrenocortical secretion at parturition

Reproduction Fertility and Development ◽

10.1071/rd9951293 ◽

1995 ◽

Vol 7 (5) ◽

pp. 1293 ◽

Cited By ~ 11

Author(s):

PT Sangild

Keyword(s):

Adrenocorticotropic Hormone ◽

Perinatal Period ◽

Postnatal Period ◽

Late Gestation ◽

Cortisol Secretion ◽

Adrenocortical Activity ◽

Pepsinogen A ◽

Newborn Pigs ◽

Neonatal Pig ◽

Stimulation Of

In many species adrenocortical activity and glucocorticoid secretion increase in late gestation and reach a peak at birth. In this study, we investigated the hypothesis that glucocorticoids stimulate the synthesis of gastric protease zymogens in the perinatal period of pigs. Pigs were delivered by Caesarean section 3-4 days prior to term (to circumvent the natural cortisol surge) and treated daily with either saline (n = 11), metyrapone (an inhibitor of cortisol synthesis, n = 12), adrenocorticotropic hormone (ACTH, n = 14) or cortisol-acetate (n = 6). The pigs were killed at 3 or 6-7 days of age and concentrations of protease zymogens in gastric mucosal extracts determined by electroimmunoassay. Zymogen contents were also determined in control (untreated) pigs from one week before birth to four weeks after birth. In control pigs, concentration of prochymosin increased rapidly before term, peaked at birth, and decreased in the postnatal period; concentrations of pepsinogen A, pepsinogen B and progastricsin were low in newborn pigs and increased in the weeks after birth. Caesarean-delivered pigs injected with saline had lower concentrations of prochymosin and pepsinogen A at 6-7 days than vaginally delivered pigs of the same postnatal age. The concentrations of these zymogens were further reduced after metyrapone treatment (depressed cortisol secretion) but were increased after treatment with ACTH (stimulated cortisol secretion) or cortisol-acetate (exogenous glucocorticoid). No consistent effects were observed for the two minor gastric protease zymogens in the pig, pepsinogen B and progastricsin. The results suggest that the normal pre-partum surge in circulating cortisol stimulates the development of the major gastric protease zymogens in the pig, prochymosin and pepsinogen A.

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