摘要:

Morphogenesis of the cardiovascular system is likely linked to its functional development. This report presents an approach to functional assessment of early cardiovascular development using parametric imaging based on videodensitometry. Trypan blue was injected into the sinus venosus of chick embryos at stage 20 (3.5 d of incubation). Images were recorded on videotape, digitized, and analyzed by a microcomputer. A sampling window was placed over the entire image, and a densogram (time-density curve) for each pixel in the window was obtained. Parameters extracted from the densogram and its derivative were plotted in form of:1) maximal image,2) peak derivative image, and3) time to peak derivative image. This approach revealed isochronal lines that divide the aortic arch and dorsal aorta into several segments. Regional flow velocity at these segments was estimated by dividing the distance between isochronal lines by the time interval. Flow velocity at the mid-systolic phase at the dorsal aorta and at the fourth aortic arch was 35.9 and 45.0 mm/s, respectively. Shear rate at the vessel wall was estimated to be 2.7 times larger at the fourth aortic arch than at the dorsal aorta. The extensive remodeling experienced by the aortic arch system compared with the dorsal aorta could be related to increased shear rate on the walls of the aortic arches.Abbreviations: DSA,digital subtraction angiography;Dmax, value of greatest dye density value along densogram;ΔDmax, value of greatest change in dye density;tΔDmax, time at which change in dye density is greatest

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

To determine the effects of inhaled NO (iNO) on pulmonary edema and lung inflammation in experimental hyaline membrane disease (HMD), we measured the effects of iNO on pulmonary hemodynamics, gas exchange, pulmonary edema, and lung myeloperoxidase (MPO) activity in extremely premature lambs (115 d of gestation, 0.78 term). In protocol 1, we measured the effects of iNO (20 ppm) on lung vascular endothelial permeability to125I-labeled albumin(indexed to blood volume using57Cr-tagged red blood cells) during 1 h(n= 10) and 3 h (n= 14) of conventional mechanical ventilation with Fio2= 1.00. In comparison with controls, iNO improved pulmonary hemodynamics and gas exchange, but did not alter lung weight-to-dry weight ratio or vascular permeability to albumin after 1 or 3 h of mechanical ventilation. To determine whether low dose iNO (5 ppm) would decrease lung neutrophil accumulation in severe HMD, we measured lung MPO activity after 4 h of mechanical ventilation with or without iNO (protocol 2). Low dose iNO improved gas exchange during 4 h of mechanical ventilation (Pao2at 4 h: 119 ± 35 mm Hg iNOversus41 ± 7 mm Hg control,p< 0.05), and reduced MPO activity by 79% (p< 0.05). We conclude that low dose iNO increases pulmonary blood flow, without worsening pulmonary edema, and decreases lung neutrophil accumulation in severe experimental HMD. We speculate that in addition to its hemodynamic effects, low dose iNO decreases early neutrophil recruitment and may attenuate lung injury in severe HMD.Abbreviations: HMD,hyaline membrane disease;PVR,pulmonary vascular resistance;QLPA, left pulmonary artery blood flow;PIP,peak inspiratory pressure;PEEP,positive end expiratory pressure;iNO,inhaled NO;MPO,myeloperoxidase;Fio2, fraction of inspired O2;Pao2, partial pressure of arterial O2;Paco2, partial pressure of arterial CO2;RBC,red blood cell;ANOVA,analysis of variance

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Proteoglycans are extracellular matrix components that appear to play important roles in lung development and in the response to injury. Decorin, a small extracellular matrix-associated proteoglycan, is known to be involved in collagen fibrillogenesis and is a likely participant in the pathogenesis of lung injury. We hypothesized that chronic exposure of the developing lung to hyperoxia would result in temporal and spatial changes in decorin expression. To determine the expression of decorin in normal and oxygen-injured lung, newborn rats were exposed to hyperoxia for 6 wk. Decorin mRNA abundance was determined using Northern hybridization analyses, and decorin expression was localized byin situhybridization and immunohistochemistry. Decorin mRNA expression in type II pneumocytes was studied using reverse transcription-polymerase chain reaction. Oxygen exposure is associated with a 77% reduction in decorin mRNA in whole lung and a decrease in decorin immunoreactivity in connective tissues surrounding large airways and blood vessels, but an increase in decorin mRNA and protein expression at the tips of alveolar septa. Studies using isolated cells indicate that macrophages and polymorphonuclear neutrophils contain decorin core protein but not decorin mRNA. Type II pneumocytes do not contain either decorin mRNA or core protein. These findings demonstrate that hyperoxic lung injury is associated with localized changes in decorin expression, changes that are not reflected in whole lung RNA studies. It is likely that regional changes in lung decorin expression are influenced by factors produced and acting locally, and that such changes may contribute to the morphologic alterations characteristic of oxygen-induced lung injury.Abbreviations: BAL,bronchoalveolar lavage;ECM,extracellular matrix;PMN,polymorphonuclear neutrophil;RT,reverse transcription;PCR,polymerase chain reaction;TGF-β,transforming growth factor-β;HEPES,N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

It was previously shown that tracheal obstruction accelerated fetal lung growth and eventually reversed the pulmonary hypoplasia in experimental diaphragmatic hernia. We have successfully developed a reversible tracheal obstruction technique in fetal sheep using balloon occlusion and showed that 3 wk of obstruction induced significant lung growth of the same magnitude as the tracheal ligation. The purpose of this study was to examine the effects of 1 and 3 wk of tracheal occlusion on the alveolar cell population with specific attention to the type II pneumocytes. We first showed that 1 wk of occlusion induced a significant increase in lung weight and in alveolar surface area. We then used the surfactant protein C (SP-C) mRNA as a specific marker of differentiated type II pneumocytes. Total RNA was isolated from fetal sheep lung with or without tracheal occlusion, and Northern blots were hybridized with a cDNA probe specific for the sheep SP-C. The results show a dramatic decrease in SP-C mRNA expression (8.8-fold,p< 0.01).In situhybridization showed a marked decrease in the density of cells expressing SP-C, as well as the amount of SP-C mRNA expressed by the cells. The effect was present as early as 1 wk of occlusion. The sparseness of type II pneumocytes was further confirmed by electron microscopy. We thus conclude that tracheal obstruction causes a profound decrease in the number of type II pneumocytes in the lungs. Given the crucial role of type II pneumocytes in surfactant production, we could speculate that, if tracheal occlusion is able to accelerate lung growth, the final product is probably surfactant-deficient.Abbreviations: SP-C,surfactant protein C;CDH,congenital diaphragmatic hernia;EM,electron microscopy

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

In immature cardiac myocytes, the sarcoplasmic reticulum is sparse. Thus, we hypothesized that sarcolemmal Ca2+influx through Na+-Ca2+exchange is the dominant mechanism for modulating intracellular Ca2+during contractions in fetal and neonatal hearts. We measured Na+-Ca2+exchange currents in neonatal and adult rabbit ventricular cells using a rapid solution switch into 0 mM external Na+. The current densities (mean ± SEM) were larger in 8 neonatal cells than in 10 adult cells (5.4 ± 1.38versus1.65 ± 0.25 pA/pF). Intracellular Ca2+transients after inhibiting the sarcoplasmic reticulum with ryanodine and thapsigargin were unchanged in 15 neonatal cells, but decreased in 15 adult cells to 78.9 ± 5.6% of baseline. When the Ca2+channels were also inhibited by adding nifedipine, Ca2+transients from Na+-Ca2+exchange were 30.0 ± 3.5% of baseline in neonatal cells compared with 13.4 ± 3.4% in adult cells. Simultaneous contractions were a larger percent of baseline in neonatal cells(85.7.6 ± 6.4%) than in adult cells (78.9 ± 5.6%) after inhibiting the sarcoplasmic reticulum, and were unmeasureable in many cells from both age groups after inhibiting the Ca2+channels as well. The ratio of Na+-Ca2+exchanger mRNA to sarcoplasmic reticulum Ca2+-ATPase mRNA levels decreased from 1.0 ± 0.13 to 0.4± 0.03 to 0.26 ± 0.02 in fetal, neonatal and adult ventricles, respectively. These measurements were consistent with a dominant role for the Na+-Ca2+exchanger in the immature heart.Abbreviations:INaCa, Na+-Ca2+exchange current;HEPES,N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid;MKRBB,modified Krebs-Ringer bicarbonate buffer

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Surfactant instillation may affect systemic and pulmonary hemodynamics. The aim of this study was to investigate whether this effect is specific to surfactant or if it can be triggered by instillation of the same volume of saline. Piglets 3-5-d-old were subjected to repeated lung lavage using 20 mL/kg 0.9% saline until the partial pressure of arterial O2was <10 kPa and partial pressure of arterial CO2was between 4.0 and 6.0 kPa with fraction of inspired oxygen (Fio2) 1.0 and peak inspiratory pressure 25 cm H2O. Porcine surfactant 200 mg/kg (80 mg/mL) or the same volume of 0.9% saline was instilled into the lungs through a feeding catheter entered through the endotracheal tube. Mean arterial blood pressure, pulmonary artery pressure, and cardiac output were measured continuously. There was a significant decrease in mean arterial blood pressure from 67 (±13) mm Hg to 52 (±18) mm Hg (p< 0.05) 210 s after instillation of surfactant. Systemic vascular resistance decreased from 0.42 (±0.18) to 0.34 (±0.18) mm Hg × mL-1× min × kg(p< 0.05) from 0 min to 180 s after instillation of surfactant. In the group receiving saline instillations there were no significant changes in mean arterial blood pressure or systemic vascular resistance. A transient but significant increase in mean pulmonary artery pressure was seen 120 s after instillation in both groups with a return to presurfactant level 240 s after instillation. Pulmonary vascular resistance increased transiently and significantly only in the group receiving surfactant. We conclude that porcine surfactant causes a decrease in systemic vascular resistance, resulting in a decrease in mean arterial blood pressure in newborn lung-lavaged piglets not seen after instillation of the same volume of saline.Abbreviations: CI,cardiac index;CO,cardiac output;CVP,central venous pressure;Fio2, fraction of inspired oxygen;FRC,functional residual capacity;I:E ratio,ratio between inspiration and expiration times;LAP,left atrial pressure;MABP,mean arterial blood pressure;Paco2, partial pressure of arterial CO2;Pao2, partial pressure of arterial O2;PAP,mean pulmonary artery pressure;PEEP,positive end expiratory pressure;PIP,peak inspiratory pressure;PVR,pulmonary vascular resistance;RDS,respiratory distress syndrome;SVR,systemic vascular resistance

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We studied the effects of exogenously administered adrenomedullin on fetal pulmonary arterial blood flow in near-term fetal sheep. The hemodynamic effects of a single injection of adrenomedullin into the left pulmonary artery were compared with those of acetylcholine; the effects of repeated injections of adrenomedullin were also studied. In seven unanesthetized fetal sheep, catheters were inserted into the left pulmonary artery to administer drugs, and into the main pulmonary and carotid arteries to measure pressures. An ultrasonic flow transducer was placed around the left pulmonary artery to measure flow continuously. A single 5-μg injection of adrenomedullin (1.90± 0.35 μg/kg of fetal weight) increased pulmonary arterial blood flow significantly, from 17 ± 10 to 120 ± 21 mL/min (p< 0.001). Two micrograms of acetylcholine (0.74 ± 0.14 μg/kg of fetal weight) also increased left pulmonary arterial blood flow, from 18± 16 to 113 ± 37 mL/min, but the effect of adrenomedullin on flow was more prolonged than was that of acetylcholine. Additionally, adrenomedullin and acetylcholine similarly decreased mean pulmonary arterial pressure by 11 and 16%, respectively, but adrenomedullin did not decrease mean carotid arterial pressure to the same degree as acetylcholine (2versus19%, respectively). Five sequentially repeated injections of adrenomedullin, once every 5 min, increased left pulmonary arterial blood flow significantly in a stepwise manner without significantly changing heart rate or mean pulmonary and carotid arterial pressures. We conclude that exogenously administered adrenomedullin is a pulmonary vasodilator in fetal sheep and has the ability to increase pulmonary blood flow significantly; there is less effect on the systemic circulation. This finding might be important in considering the therapeutic use of this peptide in the management of persistent pulmonary hypertension in the perinatal period.

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

It has previously been observed that the opioids methionine enkephalin and leucine enkephalin contribute to hypoxia-induced pial artery dilation in the piglet. It has also been demonstrated that vasopressin elicits pial artery dilation and contributes to hypoxia-induced pial dilation both directly and indirectly through the release of the above opioids. The present study was designed to investigate the role of cyclic nucleotides in this vasopressin-induced pial artery dilation and opioid release in newborn piglets equipped with a closed cranial window. Pial artery diameter and cortical periarachnoid cerebrospinal fluid (CSF) opioid and cyclic nucleotides were measured after topical application of vasopressin (40, 400, and 4000 pg/mL). Opioid levels and pial diameter were examined in the absence and presence of(Rp)-8-bromo-(Br)-cAMPs and (Rp)-8-Br-cGMPs, purported cAMP and cGMP antagonists, respectively. Periarachnoid cortical CSF cAMP concentration increased in response to topical vasopressin (1048 ± 22, 1199 ± 51, 1334 ± 61 and 1453 ± 59 fmol/mL for control, 40, 400, and 4000 pg/mL vasopressin, respectively,n= 9). Vasopressin elicited pial artery dilation, which was attenuated by(Rp)-8-Br-cAMPs (14 ± 1, 22 ± 1, and 29± 2versus8 ± 1, 12 ± 2, and 18 ± 2% dilation for 40, 400, 4000 pg/mL vasopressin, before and after(Rp)-8-Br-cAMPs, respectively,n= 7). Similarly, vasopressin-induced pial artery dilation was accompanied by elevated CSF cGMP and this dilation was attenuated in the presence of(RP)-8-Br-cGMPs (13 ± 1, 21 ± 1, and 29± 2versus5 ± 1, 9 ± 1, and 12 ± 1% dilation for 40, 400, and 4000 pg/mL vasopressin before and after(RP)-8-Br-cGMPs, respectively,n= 7). CSF opioid concentrations increased with topical vasopressin and these increases were attenuated by (RP)-8-Br-cAMPs. CSF methionine enkephalin concentrations were 1193 ± 60, 1530 ± 63, 1937 ± 89, and 2422 ± 104versus1032 ± 25, 1185 ± 261, 1337± 31, and 1519 ± 44 pg/mL for control, 40, 400, and 4000 pg/mL vasopressin before and after (RP)-8-Br-cAMPs. Similarly, vasopressin-induced CSF methionine enkephalin and leucine enkephalin release was attenuated in the presence of (RP)-8-Br-cGMPs. These data show that both cAMP and cGMP contribute to vasopressin-induced pial artery dilation and the release of the opioids methionine enkephalin and leucine enkephalin.Abbreviations: NO,nitric oxide;CSF,cerebral spinal fluid;Br,bromo;L-NNA,Nω-nitro-L-arginine;L-NMMA,Nω-monomethyl-L-arginine

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The purpose of this study was to determine whether mild hypothermia after a moderate hypoxic-ischemic insult reduces the extent of brain damage. Hypoxia was achieved in newborn piglets (n= 24; age, 14-72 h) by abrupt reduction of the inspired oxygen concentration (Fio2) to the maximum concentration (≅6%) giving low amplitude (<7.0 μV) EEG. Fio2was temporarily increased if heart rate, blood pressure, or end expiratory partial pressure of alveolar CO2(PAco2) were markedly reduced. This intermittently resulted in EEG amplitude greater than 7 μV, the EEG traces were therefore later examined to determine the duration of low amplitude EEG. After 45 min of hypoxia, the animals were randomized to normothermia (39 °C) or hypothermia (35 °C) for 3 h. Hypothermia was achieved by applying packs containing ice water. Neurologic assessments and EEG recordings were performed regularly until 3 d when the brains were perfusion fixed. Histologic damage in cortex/white matter, cerebellum, hippocampus, basal ganglia, and thalamus was graded by a pathologist blind to treatment allocation. We found that the severity of brain damage (by histopathologic and neurologic evaluation) was not significantly different when the piglets were normothermic after hypoxia compared with the group made hypothermic. Increased duration of low amplitude EEG and seizure activity were associated with increased damage. When controlling for duration of hypoxia and excluding seizures, piglets undergoing hypothermia had ≅50% less severe histopathologic damage in cortex/white matter, cerebellum, and hippocampus than those kept normothermic. Thalamus and basal ganglia had no or minor damage. It was concluded that there was no general beneficial effect of postinsult hypothermia. However, when controlling for the duration of the insult and occurrence of seizures, hypothermia reduced the severity of brain damage. This indicates a significant neuroprotective effect of 3 h of mild hypothermia on moderate, but not severe, hypoxic-ischemic insults.Abbreviations: Fio2, fraction of inspiratory oxygen;Paco2, partial pressure of alveolar CO2;Sao2, arterial oxygen saturation;MABP,mean arterial blood pressure;HR,heart rate

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The effect of allopurinol to inhibit purine metabolism via the xanthine oxidase pathway in neonates with severe, progressive hypoxemia during rescue and reperfusion with extracorporeal membrane oxygenation (ECMO) was examined. Twenty-five term infants meeting ECMO criteria were randomized in a double-blinded, placebo-controlled trial. Fourteen did not receive allopurinol, whereas 11 were treated with 10 mg/kg after meeting criteria and before cannulation, in addition to a 20-mg/kg priming dose to the ECMO circuit. Infant plasma samples before cannulation, and at 15, 30, 60, and 90 min, and 3, 6, 9, and 12 h on bypass were analyzed (HPLC) for allopurinol, oxypurinol, hypoxanthine, xanthine, and uric acid concentrations. Urine samples were similarly evaluated for purine excretion. Hypoxanthine concentrations in isolated blood-primed ECMO circuits were separately measured. Hypoxanthine, xanthine, and uric acid levels were similar in both groups before ECMO. Hypoxanthine was higher in allopurinol-treated infants during the time of bypass studied (p= 0.022). Xanthine was also elevated (p< 0.001), and uric acid was decreased (p= 0.005) in infants receiving allopurinol. Similarly, urinary elimination of xanthine increased (p< 0.001), and of uric acid decreased(p= 0.04) in treated infants. No allopurinol toxicity was observed. Hypoxanthine concentrations were significantly higher in isolated ECMO circuits and increased over time during bypass (p< 0.001). This study demonstrates that allopurinol given before cannulation for and during ECMO significantly inhibits purine degradation and uric acid production, and may reduce the production of oxygen free radicals during reoxygenation and reperfusion of hypoxic neonates recovered on bypass.Abbreviations: ECMO,extracorporeal membrane oxygenation;VA,venoarterial bypass;VV,veno-venous bypass;Fio2fractional concentration of inspired O2;Pao2partial pressure of arterial O2;Paco2partial pressure of arterial CO2

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID