Biomedical subjects

Henry L Galan

Publications and source records attributed to Henry L Galan.

11 recordsLinked to original sources

PubMed2006

Differential expression of placental and vascular endothelial nitric oxide synthase in an ovine model of fetal growth restriction.

OBJECTIVE: The objective of the study was to evaluate endothelial nitric oxide synthase concentration in the placenta, uterine, and umbilical vessels near term in an ovine model of intrauterine growth restriction induced by hyperthermia beginning in early gestation. STUDY DESIGN: Four pregnant ewes were exposed to hyperthermia conditions for 80 days beginning at 35 days gestation to induce intrauterine growth restriction. Four ewes were kept in ambient conditions as controls. Umbilical artery Doppler systolic to diastolic ratios were calculated. At 128 days gestation, fetal catheters were placed for aortic blood pressure measurements and blood gas determination. At 132 days gestation, fetal mean systemic blood pressure and gases were determined. Sheep placentomes, umbilical artery and vein, and uterine artery were assessed for endothelial nitric oxide synthase concentration and immunolocalization. RESULTS: Compared with control pregnancies, the intrauterine growth restriction pregnancies showed: (1) reduced fetal and placental weights (P < or = .01); (2) elevated systemic blood pressure (41 +/- 1.53 mm Hg versus 44.3 +/- 1.71 mm Hg; P < or = .05) and systolic to diastolic ratios (3.0 +/- 0.34 versus 3.8 +/- 0.18; P < or = .01); (3) reduced fetal O2 saturation (52.2 +/- 7.03% versus 33.05 +/- 10.98%; P < or = .008); and (4) decreased endothelial nitric oxide synthase protein concentration in the umbilical artery (2.7-fold; P < or = .01) and a trend for a decrease in the uterine artery (1.4-fold; P < or = .1). CONCLUSION: We conclude that placental endothelial nitric oxide synthase protein concentration is increased near term in our ovine model of intrauterine growth restriction, and that this increase may be secondary to hypoxia.

Animals↗

PubMed2006

Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction.

Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction (IUGR) were the focus of our study. Our objective was to test the hypothesis that the fetal ovine myocardium adapts during an IUGR gestation by increasing glucose transporter protein expression, plasma membrane-bound glucose transporter protein concentrations, and insulin signal transduction protein concentrations. Growth measurements and whole heart tissue were obtained at 55 days gestational age (dGA), 90 dGA, and 135 dGA (term = 145 dGA) in fetuses from control (C) and hyperthermic (HT) pregnant sheep. Additionally, in 135 dGA animals, arterial blood was obtained and Doppler ultrasound was used to determine umbilical artery systolic (S) and diastolic (D) flow velocity waveform profiles to calculate pulsatility (S - D/mean) and resistance (S - D/S) indices. Myocardial Glut-1, Glut-4, insulin signal transduction proteins involved in Glut-4 translocation, and glycogen content were measured. Compared to age-matched controls, HT 90-dGA fetal body weights and HT 135-dGA fetal weights and gross heart weights were lower. Heart weights as a percent of body weights were similar between C and HT sheep at 135 dGA. HT 135-dGA animals had (i) lower fetal arterial plasma glucose and insulin concentrations, (ii) lower arterial blood oxygen content and higher plasma lactate concentrations, (iii) higher myocardial Glut-4 plasma membrane (PM) protein and insulin receptor beta protein (IRbeta ) concentrations, (iv) higher myocardial glycogen content, and (v) higher umbilical artery Doppler pulsatility and resistance indices. The HT ovine fetal myocardium adapts to reduced circulating glucose and insulin concentrations by increasing plasma membrane Glut-4 and IRbeta protein concentrations. The increased myocardial Glut-4 PM and IRbeta protein concentrations likely contribute to or increase the intracellular delivery of glucose and, together with the increased lactate concentrations, enhance glycogen synthesis, which allows for maintained myocardial growth commensurate with fetal body growth.

Animals↗

PubMed2005

Fetal hypertension and abnormal Doppler velocimetry in an ovine model of intrauterine growth restriction.

OBJECTIVE: Our objective was to test the hypothesis that systemic blood pressure (BP) is increased above normal in intrauterine growth restricted (IUGR) fetal lambs with elevated umbilical artery (UmA) Doppler indices. STUDY DESIGN: Five pregnant ewes were exposed to hyperthermic conditions for 80 days beginning at 40 days' gestation (dGA) to induce IUGR. They were then placed in ambient conditions with 6 additional ewes that served as controls. Doppler indices were calculated from UmA Doppler flow velocity waveforms. At 128 dGA, fetal catheters were placed for measurement of umbilical blood flow (UBF) by an ethyl alcohol steady-state diffusion technique and for aortic BP measurements. At 132 dGA, fetal mean systemic BP and blood flow were determined. At necropsy the placental and fetal weights were recorded. UBF was normalized for fetal weight. Linear regression, F tests and t tests were performed as appropriate. P < .05 was considered significant. RESULTS: Compared with control pregnancies, the IUGR pregnancies showed: (1) reduced fetal and placental weights, (2) elevated systemic BP, (3) reduced UBF, (4) elevated UmA and aortic Doppler velocimetry indices, (5) increased resistance per 100 g placenta, and (6) decreased UmA oxygenation and increased lactic academia. The UmA Doppler index of resistance (systolic/diastolic ratio) correlated strongly with calculated resistance (R2 = 0.7). Doppler indices also correlated with systemic BP (R2 = 0.5). CONCLUSION: Ovine IUGR fetuses with high UmA Doppler indices have elevated systemic BPs. UmA Doppler indices of resistance correlate well with (1) fetal systemic BPs and (2) resistance as calculated by pressure/flow. This whole animal study shows that IUGR fetuses are hypertensive and that increased UmA Doppler resistance indices are consistent with a fetal-placental hypertensive state.

Animals↗

PubMed2004

Differences in fat and lean mass proportions in normal and growth-restricted fetuses.

OBJECTIVE: The purpose of this study was to assess fetal subcutaneous fat and lean mass areas as predictors of fetal growth restriction. STUDY DESIGN: Seventeen severe fetal growth-restricted (abdominal circumference, < 2 SD) fetuses and 20 control fetuses underwent ultrasound measurements of subcutaneous fat, lean mass, and standard biometry. Thigh subcutaneous fat and lean mass were measured on enlarged ultrasound axial images (subcutaneous fat area = total cross sectional area - lean mass area [bone + muscle areas]). Subcutaneous fat and lean mass areas were expressed as a percentage of the total cross-sectional area and were normalized to femur length and head circumference. Measurements were modeled as a function of fetal growth-restriction status and week of gestation with multiple linear regression. RESULTS: Fetal growth-restriction fetuses showed reductions in fat and lean mass (in standard biometry) and showed a disproportionate reduction in fat mass compared with lean mass. These were all associated significantly with fetal growth restriction. CONCLUSION: Fetal growth-restricted fetuses have reduced subcutaneous fat and lean mass compared with control fetuses; a further reduction occurs in subcutaneous fat concentration compared with the reduction in lean mass when fat is normalized for body size, with either head circumference or femur length. Fat-to-bone proportions may be useful in distinguishing the small for gestational age fetus who is truly fetal growth restriction from the constitutionally small fetus.

Biometry↗

PubMed2004

Defining fetal station.

OBJECTIVE: This study was undertaken to determine the definitions and beliefs regarding fetal station among pregnancy caregivers. STUDY DESIGN: Residents, nurses, and faculty at 5 teaching centers in Denver, Colo, were given surveys to determine what definitions were being used for fetal station and the perceived importance of these definitions. RESULTS: There were 243 responses from the 453 surveys. We found 4 definitions were in use: level of the presenting part in relationship to ischial spines in (1) centimeters or (2) thirds, and level of the biparietal diameter in relationship to the ischial spines in (3) centimeters or (4) thirds. Few caregivers were aware that other caregivers were using different definitions of fetal station. CONCLUSION: This lack of standardization may lead to errors in the care of laboring patients.

Colorado↗

PubMed2004

Cardiac disease in pregnancy.

This article reviews the complications, management and prognosis of cardiac disease in pregnancy.

Antibiotic Prophylaxis↗

PubMed2004

Suggestions for practice to accompany neonatal encephalopathy and cerebral palsy.

Based largely on the data in the 2003 The American College of Obstetricians and Gynecologists/American Academy of Pediatrics publication, Neonatal Encephalopathy and Cerebral Palsy, we offer 12 suggestions for practice. Familiarity with the publication and implementation of these suggested practices-by all personnel in an obstetric-neonatal unit-are important risk management techniques.

Brain Diseases↗

PubMed2003

The relationship between transplacental O2 diffusion and placental expression of PlGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction.

Placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) are involved in placental angiogenesis through interactions with the VEGFR-1 and VEGFR-2 receptors. The placenta of pregnancies whose outcome is fetal growth restriction (FGR) are characterized by abnormal angiogenic development, classically associated with hypoxia. The present study evaluated the near-term expression of this growth factor family in an ovine model of placental insufficiency-FGR, in relationship to uteroplacental oxygenation. Compared to controls, FGR pregnancies demonstrated a 37% increase in uterine blood flow (FGR vs. control, 610.86+/-48.48 vs. 443.17+/-37.39 ml min(-1) (kg fetus)(-1); P<0.04), which was associated with an increased maternal uterine venous PO2 (58.13+/-1.00 vs. 52.89+/-1.26 mmHg; P<0.02), increased umbilical artery systolic/diastolic ratio (3.90+/-0.33 vs. 2.12+/-0.26, P<0.05), and fetal hypoxia (arterial PO2; 12.79+/-0.97 vs. 18.65+/-1.6 mmHg, P<0.005). Maternal caruncle PlGF mRNA was increased in FGR (P<0.02), while fetal cotyledon VEGF mRNA was reduced (P<0.02). VEGFR-1 mRNA was also reduced in FGR fetal cotyledon (P<0.001) but was not altered in caruncle tissue. Immunoblot analysis of PlGF and VEGF demonstrated single bands at 19,000 and 18,600 Mr, respectively. Caruncle PlGF concentration was increased (P<0.04), while cotyledon VEGF was decreased (P<0.05) in FGR placentae. The data establish that uterine blood flow is not reduced in relationship to metabolic demands in this FGR model and that the transplacental PO2 gradient is increased, maintaining umbilical oxygen uptake per unit of tissue. Furthermore, these data suggest that an increased transplacental gradient of oxygen generates changes in angiogenic growth factors, which may underline the pathophysiology of the post-placental hypoxic FGR.

Acid-Base Equilibrium↗

PubMed2003

The role of fetal breathing motions compared with gasping motions in pulmonary airway uptake of intra-amniotic iron dextran.

OBJECTIVE: We hypothesized that normal fetal breathing, not acute asphyxial gasping, results in the movement of iron dextran from the amniotic cavity into the fetal lungs. In addition, the amount of iron dextran moving into the fetal lungs is cumulative with time. STUDY DESIGN: Twelve pregnant New Zealand White rabbits at 25 days of gestation were sedated and underwent ultrasound-guided injections of iron dextran into the amniotic cavities of the rabbit fetuses in both horns of each pregnant doe. Oxygen saturation was maintained at >90% in the pregnant does. The 12 does were then equally assigned to four groups on the basis of the duration of fetal exposure to the dextran (0, 8, 16, and 24 hours). At the end of each time point, one half of the fetuses received an intracardiac injection of potassium chloride to induce gasping just before necropsy. Gasping was confirmed by ultrasound scanning. At necropsy, the fetal lungs were evaluated grossly and underwent histomorphometry for iron distribution and quantification in the fetal airways. RESULTS: In the animals that received iron dextran, there was no significant difference in iron accumulation at any time point between those animals that did and did not receive potassium chloride, which suggests that acute gasping does not increase the accumulation of amniotic fluid substances in the lungs. The amount of iron in the fetal airways increased significantly with progressive length of exposure. CONCLUSION: We conclude that normal fetal breathing, not acute asphyxial gasping, resulted in the movement of intra-amniotic iron dextran into the fetal lungs and that the amount of substances that move into the fetal lungs accumulated with time.

Amniotic Fluid↗

PubMed2002

Intrauterine growth restriction (IUGR): biometric and Doppler assessment.

Intrauterine growth restriction (IUGR) is a common complication in pregnancy and influences morbidity and mortality at all stages of life. Historically, the management of IUGR has been dependent on antenatal biophysical testing and umbilical artery Doppler studies. With recent Doppler studies of the fetal central circulation, including intracardiac flows and the ductus venosus, better timing of delivery to minimize morbidity may be possible. This review will provide the reader with tools to diagnose IUGR, more accurately date the IUGR pregnancy with poor dating criteria, and better assess the condition of the IUGR fetus. A brief review of animal models of IUGR is presented to demonstrate research directions for answering human clinical questions and potentially carrying therapeutic intervention from the bench to the bedside.

Animals↗

PubMed2002

Inefficient transduction of sheep in utero after intra-amniotic injection of retroviral producer cells.

OBJECTIVE: Our purpose was to test the hypothesis that the intra-amniotic injection of a retroviral vector producer cell line into pregnant sheep will result in retrovirus-mediated transduction and stable gene transfer to the ovine fetus. STUDY DESIGN: Thirteen pregnant ewes at various gestational ages underwent amniocentesis and injection of cells producing the retrovirus vector LIRESgeo, which is derived from Maloney murine leukemia virus and encodes Escherichia coli LacZ (beta-galactosidase) as a marker gene. Pregnant ewes and fetuses were killed, and amniotic fluid, placenta, and fetal tissues were collected and assayed for transgene expression 7 to 77 days after intraamniotic injection. In addition, serum was collected and analyzed for evidence of specific immune responses against the producer cells, and amniotic fluid was collected and analyzed for deleterious effects on producer cell viability, vector production, and vector transduction. RESULTS: Only 1 of 10 fetuses exposed to the retroviral producer cells demonstrated beta-galactosidase activity that correlated with positive immunohistochemistry for LacZ in lung, trachea, pancreas, and small intestine. However, the presence of the LacZ gene could not be confirmed by polymerase chain reaction. Thus, we could not confirm transduction after any of the injections. The retroviral producer cells survived well in amniotic fluid and continued to produce high levels of retroviral vector after intra-amniotic injection, although amniotic fluid inhibited the transducing activity of the vector in a manner dependent on gestational age. CONCLUSIONS: Intra-amniotic retroviral gene transfer with the use of these amphotropic producer cells does not result in reproducible gene transfer in the ovine fetus although amniotic fluid sustains producer cell viability and vector production. Possible reasons for the inefficient transduction are discussed.

Amniocentesis↗