Preterm infants can be inadvertently exposed to high tidal volumes (V(T)) in the delivery room, causing lung inflammation and injury, but little is known about their effects on the brain. The aim of ...this study was to compare an initial 15 min of high V(T) resuscitation strategy to a less injurious resuscitation strategy on cerebral haemodynamics, inflammation and injury.
Preterm lambs at 126 d gestation were surgically instrumented prior to receiving resuscitation with either: 1) High V(T) targeting 10-12 mL/kg for the first 15 min (n = 6) or 2) a protective resuscitation strategy (Prot V(T)), consisting of prophylactic surfactant, a 20 s sustained inflation and a lower initial V(T) (7 mL/kg; n = 6). Both groups were subsequently ventilated with a V(T) 7 mL/kg. Blood gases, arterial pressures and carotid blood flows were recorded. Cerebral blood volume and oxygenation were assessed using near infrared spectroscopy. The brain was collected for biochemical and histologic assessment of inflammation, injury, vascular extravasation, hemorrhage and oxidative injury. Unventilated controls (UVC; n = 6) were used for comparison.
High V(T) lambs had worse oxygenation and required greater ventilatory support than Prot V(T) lambs. High V(T) resulted in cerebral haemodynamic instability during the initial 15 min, adverse cerebral tissue oxygenation index and cerebral vasoparalysis. While both resuscitation strategies increased lung and brain inflammation and oxidative stress, High V(T) resuscitation significantly amplified the effect (p = 0.014 and p<0.001). Vascular extravasation was evident in the brains of 60% of High V(T) lambs, but not in UVC or Prot V(T) lambs.
High V(T) resulted in greater cerebral haemodynamic instability, increased brain inflammation, oxidative stress and vascular extravasation than a Prot V(T) strategy. The initiation of resuscitation targeting Prot V(T) may reduce the severity of brain injury in preterm neonates.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Key points
Fetal growth restriction induces a haemodynamic response that aims to maintain blood flow to vital organs such as the brain, in the face of chronic hypoxaemia
Maternal sildenafil treatment ...impairs the hypoxaemia‐driven haemodynamic response and potentially compromises fetal development.
Inadequate substrate delivery to a fetus results in hypoxaemia and fetal growth restriction (FGR). In response, fetal cardiovascular adaptations redirect cardiac output to essential organs to maintain oxygen delivery and sustain development. However, FGR infants remain at risk for cardiovascular and neurological sequelae. Sildenafil citrate (SC) has been examined as a clinical therapy for FGR, but also crosses the placenta and may exert direct effects on the fetus. We investigated the effects of maternal SC administration on maternal and fetal cardiovascular physiology in growth‐restricted fetal sheep. Fetal sheep (0.7 gestation) underwent sterile surgery to induce growth restriction by single umbilical artery ligation (SUAL) or sham surgery (control, AG). Fetal catheters and flow probes were implanted to measure carotid and femoral arterial blood flows. Ewes containing SUAL fetuses were randomized to receive either maternal administration of saline or SC (36 mg i.v. per day) beginning 4 days after surgery, and continuing for 20 days. Physiological recordings were obtained throughout the study. Antenatal SC treatment reduced body weight by 32% and oxygenation by 18% in SUAL compared to AG. SC did not alter maternal or fetal heart rate or blood pressure. Femoral blood flow and peripheral oxygen delivery were increased by 49% and 30% respectively in SUALSC compared to SUAL, indicating impaired cardiovascular adaptation to chronic hypoxaemia. Antenatal SC directly impairs the fetal haemodynamic response to chronic hypoxaemia. Consideration of the consequences upon the fetus should be paramount when administering interventions to the mother during pregnancy.
Key points
Fetal growth restriction induces a haemodynamic response that aims to maintain blood flow to vital organs such as the brain, in the face of chronic hypoxaemia
Maternal sildenafil treatment impairs the hypoxaemia‐driven haemodynamic response and potentially compromises fetal development.
Key points
Approximately 5–10% pregnancies are affected by fetal growth restriction.
Preterm infants affected by fetal growth restriction have a higher incidence of bronchopulmonary dysplasia.
The ...present study is the first to measure pulmonary artery thickness and stiffness.
The findings show that impaired vasculogenesis may be a contributory factor in the higher incidence of bronchopulmonary dysplasia in preterm growth restricted infants.
The study addresses the mechanistic link between fetal programming and vascular architecture and mechanics.
Bronchopulmonary dysplasia is the most common respiratory sequelae of prematurity and histopathologically features fewer, dysmorphic pulmonary arteries. The present study aimed to characterize pulmonary artery mechanics and cardiac function in preterm infants with fetal growth restriction (FGR) compared to those appropriate for gestational age (AGA) in the early neonatal period. This prospective study reviewed 40 preterm infants between 28 to 32 weeks gestational age (GA). Twenty infants had a birthweight <10th centile and were compared with 20 preterm AGA infants. A single high resolution echocardiogram was performed to measure right pulmonary arterial and right ventricular (RV) indices. The GA and birthweight of FGR and AGA infants were 29.8 ± 1.3 vs. 30 ± 0.9 weeks (P = 0.78) and 923.4 g ± 168 vs. 1403 g ± 237 (P < 0.001), respectively. Assessments were made at 10.5 ± 1.3 days after birth. The FGR infants had significantly thicker right pulmonary artery inferior wall (843.5 ± 68 vs. 761 ± 40 μm, P < 0.001) with reduced pulsatility (51.6 ± 7.6 μm vs. 59.7 ± 7.5 μm, P = 0.001). The RV contractility fractional area change (28.7 ± 3.8% vs 32.5 ± 3.1%, P = 0.001), tricuspid annular peak systolic excursion (TAPSE) (5.2 ± 0.3% vs. 5.9 ± 0.7%, P = 0.0002) and myocardial performance index (0.35 ± 0.03 vs. 0.28 ± 0.02, P < 0.001) was significantly impaired in FGR infants. Significant correlation between RV longitudinal contractility (TAPSE) and time to peak velocity/RV ejection time (measure of RV afterload) was noted (r2 = 0.5, P < 0.001). Altered pulmonary vascular mechanics and cardiac performance reflect maladaptive changes in response to utero‐placental insufficiency. Whether managing pulmonary vascular disease will alter clinical outcomes remains to be studied prospectively.
Key points
Approximately 5–10% pregnancies are affected by fetal growth restriction.
Preterm infants affected by fetal growth restriction have a higher incidence of bronchopulmonary dysplasia.
The present study is the first to measure pulmonary artery thickness and stiffness.
The findings show that impaired vasculogenesis may be a contributory factor in the higher incidence of bronchopulmonary dysplasia in preterm growth restricted infants.
The study addresses the mechanistic link between fetal programming and vascular architecture and mechanics.
Contaminated Rivers Miller, Jerry R; Orbock Miller, Suzanne M
2007, 2007-07-15
eBook
This book provides an introductory understanding of fluvial geomorphic principles. It examines how these principles can be integrated with geochemical data to cost-effectively characterize, assess ...and remediate contaminated rivers.
Cerebral palsy (CP) is a permanent motor disorder that results from brain injury and neuroinflammation during the perinatal period. Mesenchymal stromal cells (MSCs) have been explored as a therapy in ...multiple adult neuroinflammatory conditions. Our study examined the therapeutic benefits of intranasal delivery of human umbilical cord tissue (UC) derived-MSCs in a rat model of neonatal hypoxic-ischemic (HI) brain injury. To do this, HI was performed on postnatal day 10 Sprague-Dawley rat pups via permanent ligation of the left carotid artery, followed by a hypoxic challenge of 8% oxygen for 90 min. A total of 200,000 UC-MSCs (10 million/kg) were administered intranasally 24 h post-HI. Motor control was assessed after seven days, followed by post-mortem. Analysis included brain immunohistochemistry, gene analysis and serum cytokine measurement. Neonatal HI resulted in brain injury with significant loss of neurons, particularly in the hippocampus. Intranasal administration of UC-MSCs significantly reduced the loss of brain tissue and increased the number of hippocampal neurons. HI significantly upregulated brain inflammation and expression of pro-inflammatory cytokines, while intranasal UC-MSCs significantly reduced markers of neuroinflammation. This study demonstrated that a clinically relevant dose (10 million/kg) of UC-MSCs was neuroprotective following HI by restoring neuronal cell numbers and reducing brain inflammation. Therefore, intranasal delivery of UC-MSCs may be an effective therapy for neonatal brain injury.
It is well understood that hypoxic-ischemic (HI) brain injury during the highly vulnerable perinatal period can lead to cerebral palsy, the most prevalent cause of chronic disability in children. ...Recently, human clinical trials have reported safety and some efficacy following treatment of cerebral palsy using umbilical cord blood (UCB) cells. UCB is made up of many different cell types, including endothelial progenitor cells (EPCs), T regulatory cells (Tregs), and monocyte-derived suppressor cells (MDSCs). How each cell type contributes individually towards reducing neuroinflammation and/or repairing brain injury is not known. In this study, we examined whether human (h) UCB, or specific UCB cell types, could reduce peripheral and cerebral inflammation, and promote brain repair, when given early after perinatal HI brain injury.
HI brain injury was induced in postnatal day (PND) 7 rat pups and cells were administered intraperitoneally on PND 8. Behavioral testing was performed 7 days post injury, and then, brains and spleens were collected for analysis.
We found in vitro that all UCB cell types, except for EPCs, were immunomodulatory. Perinatal HI brain injury induced significant infiltration of CD4+ T cells into the injured cerebral hemisphere, and this was significantly reduced by all hUCB cell types tested. Compared to HI, UCB, Tregs, and EPCs were able to reduce motor deficits, reduce CD4+ T cell infiltration into the brain, and reduce microglial activation. In addition to the beneficial effects of UCB, EPCs also significantly reduced cortical cell death, returned CD4+ T cell infiltration to sham levels, and reduced the peripheral Th1-mediated pro-inflammatory shift.
This study highlights that cells found in UCB is able to mediate neuroinflammation and is an effective neuroprotective therapy. Our study also shows that particular cells found in UCB, namely EPCs, may have an added advantage over using UCB alone. This work has the potential to progress towards tailored UCB therapies for the treatment of perinatal brain injury.
To assess cardiac morphology and function in preterm infants with fetal growth restriction (FGR) compared with an appropriate for gestational age cohort, and to ascertain clinical correlation with ...neonatal sequelae.
With informed consent, 20 infants born between 28 and 32 weeks of gestational age and birthweight (BW) <10th percentile were compared using conventional and tissue Doppler echocardiography with 20 preterm appropriate for gestational age infants. Total duration of respiratory support was recorded.
The gestational age and BW of the infants with FGR and appropriate for gestational age infants were 29.8 ± 1.3 weeks vs 30 ± 0.9 weeks (P = .78) and 923.4 ± 168 g vs 1403 ± 237 g (P < .001), respectively. Preterm infants with FGR had significantly greater interventricular septal hypertrophy, greater free wall thickening, and lower sphericity indices (1.53 ± 0.15 vs 1.88 ± 0.2; P < .001), signifying globular and hypertrophied hearts. The transmitral E/A ratio and isovolumic relaxation time, markers of diastolic function, were significantly increased in the FGR cohort (0.84 ± 0.05 vs 0.78 ± 0.03 P < .001 and 61.4 ± 4.1 ms vs 53.2 ± 3.2 ms P < .001, respectively). Ejection fraction, as measured by the rate corrected mean velocity of circumferential fiber shortening was reduced (1.93 ± 0.4 circ/second vs 2.77 ± 0.5 circ/second; P < .001) in the FGR cohort. On follow-up, the total duration of respiratory support was significantly longer in the FGR cohort, and correlated with tissue Doppler E/E' (r = 0.65; P = .001), mean velocity of circumferential fiber shortening (r = -0.64; P = .001) and mitral annular peak systolic excursion (r = -0.57; P = .008).
Preterm infants with FGR have altered cardiac function evident within days after birth, which is associated with respiratory sequelae.
Purpose
Lymphedema affects 20–30 % of women following breast cancer treatment. However, even when women are informed, they do not necessarily adhere to recommended lymphedema self-management ...regimens. Utilizing the Cognitive-Social Health Information Processing framework, we assessed the cognitive and emotional factors influencing adherence to lymphedema risk management.
Methods
Women with breast cancer who had undergone breast and lymph node surgery were recruited through the Fox Chase Cancer Center breast clinic. Participants (
N
= 103) completed measures of lymphedema-related perceived risk, beliefs and expectancies, distress, self-regulatory ability to manage distress, knowledge, and adherence to risk management behaviors. They then received the American Cancer Society publication “Lymphedema: What Every Woman with Breast Cancer Should Know.” Cognitive and affective variables were reassessed at 6 and 12 months post-baseline.
Results
Maximum likelihood multilevel model analyses indicated that overall adherence increased over time, with significant differences between baseline and 6- and 12-month assessments. Adherence to wearing gloves was significantly lower than that for all other behaviors except electric razor use. Distress significantly decreased, and knowledge significantly increased, over time. Greater knowledge, higher self-efficacy to enact behaviors, lower distress, and higher self-regulatory ability to manage distress were associated with increased adherence.
Conclusions
Women who understand lymphedema risk management and feel confident in managing this risk are more likely to adhere to recommended strategies. These factors should be rigorously assessed as part of routine care to ensure that women have the self-efficacy to seek treatment and the self-regulatory skills to manage distress, which may undermine attempts to seek medical assistance.
Fetal growth restriction (FGR) is a common complication of pregnancy, resulting in a fetus that fails to reach its genetically determined growth potential. Whilst the fetal cardiovascular response to ...acute hypoxia is well established, the fetal defence to chronic hypoxia is not well understood due to experiment constraints. Growth restriction results primarily from reduced oxygen and nutrient supply to the developing fetus, resulting in chronic hypoxia. The fetus adapts to chronic hypoxia by redistributing cardiac output via brain sparing in an attempt to preserve function in the developing brain. This review highlights the impact of brain sparing on the developing fetal cardiovascular and cerebrovascular systems, as well as emerging long-term effects in offspring that were growth restricted at birth. Here, we explore the pathogenesis associated with brain sparing within the cerebrovascular system. An increased understanding of the mechanistic pathways will be critical to preventing neuropathological outcomes, including motor dysfunction such as cerebral palsy, or behaviour dysfunctions including autism and attention-deficit/hyperactivity disorder (ADHD).
Melatonin (MLT) is an endogenous hormone that controls circadian cycle. MLT has additional important properties that make it appealing as a neuroprotective agent-it is a potent anti-oxidant, with ...anti-apoptotic and anti-inflammatory properties. MLT is safe for administration during pregnancy or to the newborn after birth, and can reduce white matter brain injury under conditions of chronic fetal hypoxia. Accordingly, in the current study, we examined whether an intermediate dose of MLT could restore white matter brain development when administered
an acute hypoxic ischemic (HI) insult in preterm fetal sheep. Fifteen fetal sheep at 95-98 days gestation were instrumented with femoral artery and vein catheters, and a silastic cuff placed around the umbilical cord. At 102 days gestation, the cuff was inflated, causing complete umbilical cord occlusion for 25 min in 10 fetuses, to induce acute severe HI. Five HI fetuses received intravenous MLT for 24 h beginning at 2 h after HI. The remaining five fetuses were administered saline alone. Ten days after HI, the fetal brain was collected from each animal and white and gray matter neuropathology assessed. HI caused a significant increase in apoptotic cell death (TUNEL+), activated microglia (Iba-1+), and oxidative stress (8-OHdG+) within the subventricular and subcortical white matter. HI reduced the total number of oligodendrocytes and CNPase+ myelin density. MLT administration following HI decreased apoptosis, inflammation and oxidative stress within the white matter. MLT had intermediate benefits for the developing white matter: it increased oligodendrocyte cell number within the periventricular white matter only, and improved CNPase+ myelin density within the subcortical but not the striatal white matter. MLT administration following HI was also associated with improved neuronal survival within the cortex. Neuropathology in preterm infants is complex and mediated by multiple mechanisms, including inflammation, oxidative stress and apoptotic pathways. Treatment with MLT presents a safe approach to neuroprotective therapy in preterm infants but appears to have brain region-specific benefits within the white matter.
PDF
