Lung Development in the Fetal Guinea Pig: Surfactant, Morphology, and Premature Viability

Sosenko, Ilene R.S.; Frank, Lee

doi:10.1203/00006450-198705000-00001

Cited by 20 publications

(13 citation statements)

References 15 publications

(17 reference statements)

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“…However, the demonstrated decreased viability and significant physiologic immaturity of these preterm neonates suggest an earlier age equivalency. This is supported by previous studies in the guinea pig that have assessed lung development in the fetal guinea pig and suggest that pups born before 66 d GA show considerable lack of development, demonstrated by lung growth and development, and that guinea pig neonates born at <88% completed gestation cannot survive with non-invasive interventions (23). These findings are consistent with the significantly increased mortality of preterm guinea pig neonates observed in this study.…”

Section: Discussionsupporting

confidence: 82%

“…Previous studies have concluded that lung growth and development parallels the overall development of a species at birth (24). In a previous study of lung development, fetal guinea pigs at 61 d gestation had lung morphology indicative of the saccular stage of lung development, which is seen in the human neonate from approximately 24 wk of GA through to term (23). Viability and support levels in our neonatal guinea pigs suggest that they are more physiologically equivalent to a human infant born at approximately 29 wk completed gestation because approximately half of the infants born at this GA could be expected to survive with only our limited interventions.…”

Section: Discussionmentioning

confidence: 99%

“…As a percentage of completed gestation (87%), this is the equivalent of a human infant born in the late preterm period (approximately 34.5 wk GA). This time point was chosen because it is the earliest GA that guinea pig pups can be kept alive with non-invasive support (23). Guinea pigs have been shown to be markedly resistant to glucocorticoids such as betamethasone, with significantly decreased glucocorticoid receptor binding affinity (34).…”

Section: Cesarean Section Deliverymentioning

confidence: 99%

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The guinea pig as an animal model for studying perinatal changes in microvascular function

et al. 2011

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INTRODUCTION: Microvascular dysfunction, characterized by inappropriate vasodilatation and high blood flow in the peripheral microcirculation, is linked to physiologic instability and poor outcome in neonates. specifically, preterm neonates have significantly higher levels of baseline microvascular blood flow than term neonates at 24 h postnatal age. Because of similarities between human and guinea pig endocrine profiles and maturity at birth, we hypothesized that preterm guinea pig neonates would provide a suitable model for studying the mechanisms underlying transitional microvascular function. RESULTS: Guinea pigs that were delivered preterm showed immaturity and had markedly reduced viability. Baseline microvascular blood flow was significantly higher in preterm animals than in term animals. No effect of intrauterine growth restriction or birth weight on baseline microvascular blood flow was observed in either preterm or term animals. DISCUSSION: These results are consistent with recent clinical findings and support the use of the guinea pig as a suitable model for future studies of the mechanisms underlying perinatal microvascular behavior. METHODS: Guinea pigs were delivered either prematurely or at term. Laser Doppler flowmetry was used to study microvascular blood flow at 23 h postnatal age. In term infants, the circulation undergoes rapid and extensive changes in the initial hours of extrauterine life to allow the infant to effectively deal with extrauterine systemic vascular resistance and hence provide normal and adequate perfusion of tissues (1-3). The transitional circulation of preterm neonates (especially those born at ≤30 wk gestation) differs significantly from infants born at full term. In the preterm infant, several crucial physiologic responses to extrauterine life are commonly delayed, allowing for persistence of atrial and ductal shunting and inappropriate blood flow throughout the periphery during the perinatal period (4)(5)(6)(7)(8).Previous studies in preterm infants suggest that abnormal microvascular tone, characterized by inappropriate vasodilatation of the peripheral microvasculature, may contribute to the development of circulatory compromise (4,8). These studies found that the functional integrity of the microvasculature (including appropriate control of vasodilatation) in preterm neonates is significantly altered as compared with neonates born at later gestational ages (GAs). Very preterm neonates (born at 24-28 wk GA) are known to have significantly higher microvascular blood flow at 24 h postnatal age than preterm neonates born at 29-34 wk GA and neonates born at term. High baseline microvascular blood flow in premature infants is significantly correlated with clinical illness severity and poor outcome in the immediate postnatal period (4,9). Such dysfunction in the microvasculature is also a well-established observation associated with the onset of other causes of multisystem organ failure in neonates (10).In addition to disorders relating to short gestation, intrauterine growt...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Cesarean Section Deliverymentioning

confidence: 99%

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The guinea pig as an animal model for studying perinatal changes in microvascular function

et al. 2011

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“…P4 has been shown to play a role in lung development (Beyer et al 2003;Trotter et al 2006Trotter et al , 2009 as well as in neurological development (Wagner 2008;Yawno et al 2014). These two organs manifest prolonged development in humans (and in guinea pig; Sosenko and Frank 1987), as evidenced by a majority of the defects from preterm birth being of neurological and pulmonary nature. It is tempting to speculate that the evolution of a metabolically costly brain (Clancy et al 2007), in particular given its growth spurt immediately following birth, may require lungs with exceptional capacity and long development.…”

Section: What May Drive Different Levels Of Progesterone Across Species?mentioning

confidence: 99%

Genomics of Preterm Birth

Swaggart

Pavličev

Muglia

2015

Cold Spring Harbor Perspectives in Medicine

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The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms.

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“…During the next stage, the stage of alveolarization, the gasexchange surface increases dramatically due to the subdivision of the existing airspaces (sacculi) by the formation of new inter-airspace walls resulting in the appearance of the alveoli. Depending on species, alveolarization can be pre-or postnatal: in precocial animals like guinea pigs (36) and sheep (1), alveolar formation starts well before birth, and at term their lungs appear almost mature. In altricial species, alveolar formation is rather a postnatal event, like in rats (4,6), mice (2), and humans (46,47).…”

mentioning

confidence: 99%

Rat lungs show a biphasic formation of new alveoli during postnatal development

Tschanz

Salm

Roth‐Kleiner

et al. 2014

Journal of Applied Physiology

109

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Roughly 90% of the gas-exchange surface is formed by alveolarization of the lungs. To the best of our knowledge, the formation of new alveoli has been followed in rats only by means of morphological description or interpretation of semiquantitative data until now. Therefore, we estimated the number of alveoli in rat lungs between postnatal days 4 and 60 by unambiguously counting the alveolar openings. We observed a bulk formation of new alveoli between days 4 and 21 (17.4 times increase from 0.8 to 14.3 millions) and a second phase of continued alveolarization between days 21 and 60 (1.3 times increase to 19.3 million). The (number weighted) mean volume of the alveoli decreases during the phase of bulk alveolarization from ∼593,000 μm(3) at day 4 to ∼141,000 μm(3) at day 21, but increases again to ∼298,000 μm(3) at day 60. We conclude that the "bulk alveolarization" correlates with the mechanism of classical alveolarization (alveolarization before the microvascular maturation is completed) and that the "continued alveolarization" follows three proposed mechanisms of late alveolarization (alveolarization after microvascular maturation). The biphasic pattern is more evident for the increase in alveolar number than for the formation of new alveolar septa (estimated as the length of the free septal edge). Furthermore, a striking negative correlation between the estimated alveolar size and published data on retention of nanoparticles was detected.

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Lung Development in the Fetal Guinea Pig: Surfactant, Morphology, and Premature Viability

Cited by 20 publications

References 15 publications

The guinea pig as an animal model for studying perinatal changes in microvascular function

The guinea pig as an animal model for studying perinatal changes in microvascular function

Genomics of Preterm Birth

Rat lungs show a biphasic formation of new alveoli during postnatal development

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