Search PubMed⌕ Search

Biomedical subjects

Richard Harding

Publications and source records attributed to Richard Harding.

At least 19 recordsLinked to original sources
PubMed2007

Vulnerability of dopaminergic amacrine cells and optic nerve myelination to prenatal endotoxin exposure.

PURPOSE: Intrauterine infection has been linked to preterm delivery and neurologic injury. The purpose of this study was to investigate the effects of fetal inflammation induced by exposure to endotoxin on the structure and neurochemistry of the retina and optic nerve. METHODS: The bacterial endotoxin, lipopolysaccharide (LPS), was administered to fetal sheep at approximately 0.65 of the approximately 147-day gestation period via repeated bolus doses (1 microg/kg per day) over 5 days, with fetal retinas and optic nerves assessed 10 days after the first LPS exposure. RESULTS: In the retina, the total number of tyrosine hydroxylase immunoreactive (TH-IR), dopaminergic amacrine cells was reduced (P < 0.05) in LPS-exposed compared with control fetuses. There was no difference in the number of ChAT-, substance P-, or NADPH-d-positive amacrine cells. The total number of myelinated axons in the optic nerve was not different (P > 0.05) between groups; however, the myelin sheath was thinner (P < 0.05) in LPS-exposed fetuses. CONCLUSIONS: Prenatal exposure to repeated doses of endotoxin results in alterations to the retina and optic nerve with specific effects on dopaminergic neurons and myelination, respectively. These findings could have implications for visual function.

Amacrine Cells↗
PubMed2006

Intrauterine growth restriction delays cardiomyocyte maturation and alters coronary artery function in the fetal sheep.

There is now extensive evidence suggesting that intrauterine perturbations are linked with an increased risk of developing cardiovascular disease. Human epidemiological studies, supported by animal models, have demonstrated an association between low birth weight, a marker of intrauterine growth restriction (IUGR), and adult cardiovascular disease. However, little is known of the early influence of IUGR on the fetal heart and vessels. The aim of this study was to determine the effects of late gestational IUGR on coronary artery function and cardiomyocyte maturation in the fetus. IUGR was induced by placental embolization in fetal sheep from 110 to 130 days of pregnancy (D110-130); term approximately D147; control fetuses received saline. At necropsy (D130), wire and pressure myography was used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in small branches of left descending coronary arteries. Myocardium was dissociated for histological analysis of cardiomyocytes. At D130, IUGR fetuses (2.7 +/- 0.1 kg) were 28% lighter than controls (3.7 +/- 0.3 kg; P = 0.02). Coronary arteries from IUGR fetuses had enhanced responsiveness to the vasoconstrictors, angiotensin II and the thromboxane analogue U46619, than controls (P < 0.01). Endothelium-dependent and -independent relaxations were not different between groups. Coronary arteries of IUGR fetuses were more compliant (P = 0.02) than those of controls. The incidence of cardiomyocyte binucleation was lower in the left ventricles of IUGR fetuses (P = 0.02), suggestive of retarded cardiomyocyte maturation. We conclude that late gestational IUGR alters the reactivity and mechanical wall properties of coronary arteries and cardiomyocyte maturation in fetal sheep, which could have lifelong implications for cardiovascular function.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2006

Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of fetal and maternal sheep.

Maternal ethanol intake during pregnancy impairs fetal growth, but mechanisms are not clearly defined. Reduced IGF abundance or bioavailability in the fetus and/or mother may contribute to this growth restriction. We hypothesized that an episode of acute ethanol exposure, mimicking binge drinking would restrict fetal growth and perturb the maternal and fetal IGF axes. Pregnant sheep were infused intravenously with saline or ethanol (1 g/kg maternal wt) over 1 h, on days 116, 117, and 118 of gestation (start of 1st infusion = time 0, term is 147 days). Maternal and fetal plasma IGF and IGF-binding protein (IGFBP) concentrations were measured before and after each infusion. Compared with controls, ethanol exposure reduced fetal weight at day 120 by 19%, transiently reduced maternal plasma IGF-I (-35%) at 30 h, and decreased fetal plasma IGF-II (-28%) from 24 to 54 h after the first infusion. Ethanol exposure did not alter maternal or fetal plasma concentrations of IGFBP-2 and IGFBP-3, measured by Western ligand blotting. We conclude that suppression of maternal and fetal IGF abundance may contribute to fetal growth restriction induced by acute or binge ethanol exposure.

Animals↗
PubMed2006

Sources of amniotic fluid erythropoietin during normoxia and hypoxia in fetal sheep.

OBJECTIVE: Erythropoietin is present in human amniotic fluid and has been suggested as a marker of fetal hypoxia. The objectives of the present study were to determine whether erythropoietin is present in ovine amniotic fluid, fetal urine, and/or lung liquid and whether concentrations in these compartments change in parallel with endogenous fetal plasma erythropoietin concentration when the latter is increased experimentally. STUDY DESIGN: In late gestation chronically catheterized fetal sheep, samples of amniotic fluid and plasma, urine and plasma, lung liquid, amniotic fluid, and plasma were collected before and up to 7 days after induction of 4 types of fetal hypoxia: (1) acute anemic hypoxia that was induced by a single fetal hemorrhage, (2) progressive anemic hypoxia that was induced by daily exchange transfusion, (3) acute hypoxic hypoxia that was induced by the reduction of maternal inspired oxygen content, or (4) chronic placental insufficiency that was induced by daily umbilicoplacental embolization for 4 days. Erythropoietin concentrations were determined by radioimmunoassay. Statistical testing included analysis of variance and least squares regression. RESULTS: Under basal, nonhypoxic conditions, amniotic fluid erythropoietin concentration averaged 33.2% +/- 1.6% (SE) of fetal plasma erythropoietin concentration, and basal fetal urine and lung liquid erythropoietin concentrations ranged from low (<10% of plasma concentration) to nondetectable. Unlike the strong correlation in humans, basal amniotic fluid and plasma erythropoietin concentrations were correlated only weakly (r = 0.259; r2 = 6.7%; P = .0027; n = 132). Amniotic fluid erythropoietin concentration approximately doubled after 12 hours of severe hypoxic hypoxia or after 24 hours of embolization-induced severe hypoxia but was unchanged after 12 hours of mild-moderate hypoxic hypoxia or 24 hours of anemic hypoxia. Concomitant fetal plasma erythropoietin concentrations increased to 28.1 +/- 5.3, 12.5 +/- 2.7, 10.8 +/- 4.6, and 10.0 +/- 1.3 times basal values, respectively. During progressive fetal anemia, urinary erythropoietin concentration increased almost 10-fold (P = .0023) but remained a small fraction (3.7% +/- 0.4%) of plasma concentration; at 12 hours of hypoxic hypoxia, lung liquid erythropoietin concentration did not vary with the severity of the hypoxia and remained low relative to plasma concentration (4.2% +/- 2.1%). CONCLUSION: Erythropoietin is present in ovine amniotic fluid, urine, and lung liquid. With only 3 potential sources, the fetal membranes appear to be the primary source of amniotic fluid erythropoietin in the nonhypoxic ovine fetus because basal urine and lung liquid erythropoietin concentrations are much lower than amniotic fluid concentrations. Although unchanged during mild-to-moderate fetal hypoxia, amniotic fluid erythropoietin concentration increases modestly during severe fetal hypoxia. In sheep, fetal urinary erythropoietin may contribute to this rise in amniotic fluid erythropoietin concentration during severe hypoxia, because fetal urinary and plasma concentrations increase in parallel during anemia.

Amniotic Fluid↗
PubMed2006

Validity of measures of pain and symptoms in HIV/AIDS infected households in resources poor settings: results from the Dominican Republic and Cambodia.

BACKGROUND: HIV/AIDS treatment programs are currently being mounted in many developing nations that include palliative care services. While measures of palliative care have been developed and validated for resource rich settings, very little work exists to support an understanding of measurement for Africa, Latin America or Asia. METHODS: This study investigates the construct validity of measures of reported pain, pain control, symptoms and symptom control in areas with high HIV-infected prevalence in Dominican Republic and Cambodia Measures were adapted from the POS (Palliative Outcome Scale). Households were selected through purposive sampling from networks of people living with HIV/AIDS. Consistencies in patterns in the data were tested used Chi Square and Mantel Haenszel tests. RESULTS: The sample persons who reported chronic illness were much more likely to report pain and symptoms compared to those not chronically ill. When controlling for the degrees of pain, pain control did not differ between the chronically ill and non-chronically ill using a Mantel Haenszel test in both countries. Similar results were found for reported symptoms and symptom control for the Dominican Republic. These findings broadly support the construct validity of an adapted version of the POS in these two less developed countries. CONCLUSION: The results of the study suggest that the selected measures can usefully be incorporated into population-based surveys and evaluation tools needed to monitor palliative care and used in settings with high HIV/AIDS prevalence.

Journal Article↗
PubMed2006

Increased vascular endothelial growth factor and receptors: relationship to angiogenesis in asthma.

RATIONALE: Increased vascularity is a feature of airway remodeling in asthma with the potential to contribute to a number of functional abnormalities in this chronic disease. Although various growth factors have been implicated in modulating vascularity, the important contributors in vivo are still being elucidated. The most likely candidate is vascular endothelial growth factor (VEGF). OBJECTIVES: We have examined VEGF and its receptors, VEGFR1 and VEGFR2, and angiopoietin-1 (Ang1) in the airways of subjects with asthma and contrasted these results with findings in normal control subjects. We aimed to explore whether these powerful angiogenic factors were expressed at elevated levels in asthmatic airways. METHODS: We obtained biopsy and bronchoalveolar lavage samples from 35 subjects with mild to moderate asthma and from 22 normal control subjects. MEASUREMENTS: We performed immunohistochemistry and image analysis to obtain quantitative measures of VEGF, VEGFR1, VEGFR2, and Ang1 staining in airway biopsies, and ELISA to assess VEGF concentration in the bronchoalveolar lavage fluid. RESULTS: VEGF staining and VEGF levels in bronchoalveolar lavage fluid were elevated in the airways of subjects with asthma and were related to the number of vessels; Ang1 staining was similarly increased. VEGFR1 was slightly higher in subjects with asthma and the VEGFR1:VEGFR2 ratio was significantly higher in subjects with asthma. We observed angiogenic sprouts (i.e., early-forming vascular structures) that were increased in number in subjects with asthma. CONCLUSIONS: Our findings suggest that VEGF, its receptors, and Ang1 are likely to be important in vascular changes in the airways of patients with asthma. Further, there are observable structures in the vessel walls of asthmatic airways that could present ongoing evidence of increased angiogenic activity.

Adult↗
PubMed2006

Effects of antenatal corticosteroid treatment on pulmonary ventilation and circulation in neonatal lambs with hypoplastic lungs.

Our aim was to determine whether antenatal corticosteroids improve perinatal adaptation of the pulmonary circulation in lambs with lung hypoplasia (LH). LH was induced in 12 ovine fetuses between 105 and 140 days gestation (term approximately 147 days); in 6 of these the ewe was given a single dose of betamethasone (11.4 mg im) 24 hr before delivery (LH + B). All lambs, including a control group (n = 6), were delivered at approximately 140 days and ventilated for 2 hr during which arterial pressures, pulmonary blood flow (PBF), and ventilating pressure and flow were recorded. During ventilation, respiratory system compliance was lower in both LH + B and LH groups than in controls. Pulmonary vascular resistance (PVR) was lower in LH + B lambs than in LH lambs and similar to controls; PBF was reduced in LH lambs but was restored to control levels by betamethasone. The mean density of small arteries of LH + B lambs was similar to that of LH lambs (P = 0.06) and lower than in controls; the thickness of the media of small pulmonary arteries from LH + B lambs was similar to that in LH lambs and thicker than in controls. VEGF mRNA levels were not different between groups. PDGF mRNA levels in LH + B lambs were higher than in LH lambs; a similar trend (P = 0.06) was seen for PECAM-1. SP-C mRNA levels were greater in both LH and LH + B lambs than in controls. Effects of betamethasone were greater on indices of pulmonary circulation than ventilation. We conclude that a single dose of maternal betamethasone 24 hr prior to birth has significant favorable effects on the postnatal adaptation of the pulmonary circulation in lambs with LH.

Animals↗
PubMed2006

Chronic endotoxin exposure causes brain injury in the ovine fetus in the absence of hypoxemia.

OBJECTIVE: Intrauterine infection has been linked to brain injury in human infants, although the mechanisms are not fully understood. We recently showed that repeated acute exposure of preterm fetal sheep to bacterial endotoxin (lipopolysaccharide [LPS]) results in fetal hypoxemia, hypotension, increased systemic proinflammatory cytokines, and brain damage, including white matter injury. However, it is not clear whether this injury is caused by reduced cerebral oxygen delivery or inflammatory pathways independent of hypoxia. The aim of the present study was to determine the effects on the fetal brain and placenta of a chronic intrauterine inflammatory state, induced by LPS infusion into the fetal circulation, a model that did not cause hypoxia. METHODS: At 0.65 of term, eight catheterized fetal sheep received intravenous infusions of LPS (5 to 15 mug) over 5 days; control fetuses received saline. Fetal physiologic responses were monitored throughout the infusion. Fetal brain and placental tissues were examined histologically 6 days after the conclusion of the infusion. RESULTS: LPS infusions did not result in physiologically significant alterations to fetal blood gases or mean arterial pressure; however, plasma proinflammatory cytokine levels were elevated. Following LPS exposure there was no difference in fetal body or brain weights (P >.05); placental weight was reduced (P <.05), consistent with reduced placentome cross-sectional area (P <.05). In the cerebral hemispheres subcortical white matter injury was present in six LPS-exposed fetuses and included axonal damage, microgliosis, oligodendrocyte injury, and increased beta amyloid precursor protein (beta-APP) expression. CONCLUSIONS: Chronic, systemic exposure of the fetus to LPS resulted in fetal brain damage in the absence of hypoxemia or hypotension, although the resulting injury was less severe than following repeated acute exposure.

Amyloid beta-Protein Precursor↗
PubMed2006

Chronic exposure to intra-amniotic lipopolysaccharide affects the ovine fetal brain.

OBJECTIVE: Fetal brain injury is associated with chorioamnionitis, which is often present without signs of overt infection or fetal compromise. We aimed to determine if prolonged exposure to intrauterine inflammation caused by intra-amniotic infusion of lipopolysaccharide (LPS) would affect the fetal brain. METHODS: At 80 days of pregnancy ewes bearing singletons had osmotic pumps implanted intra-amniotically to infuse Escherichia coli LPS (055:B5; n = 8) or saline (n = 7) for 28 days. At delivery (110 days), umbilical arterial blood and chorioamnion were assessed for inflammation; cytokine concentrations (interleukin [IL]-6 and IL-8) in amniotic fluid and fetal and maternal plasma were measured. The fetal cerebral hemispheres were examined for gross anatomical changes and the number of activated microglia/macrophages, astrocytes, and oligodendrocytes estimated after immunohistochemical staining. RESULTS: Intra-amniotic administration of LPS caused chorioamnionitis, fetal leucocytosis, and a moderate to extensive infiltration of activated microglia/macrophages in the subcortical white matter in six of eight fetuses; the remaining two fetuses were less affected. Within these focal regions of damage there was an attenuation of astrocytic processes, axonal injury, and a reduction in the number of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) immunoreactive oligodendrocytes in areas of extensive focal damage. In control fetuses there was mild (3/7) or no infiltration of activated microglia/macrophages in the subcortical white matter. Overall the infiltration of activated microglia/macrophages in the white matter was significantly greater in LPS-exposed fetuses compared to controls. In regions devoid of injury, the number of oligodendrocytes and astrocytes was not different between groups, nor was there a difference in the volume of cerebral white matter or density of blood vessels within the white matter. Amniotic fluid IL-6 and IL-8, and maternal plasma IL-8 concentrations were significantly increased by LPS infusion. CONCLUSIONS: An increase in inflammatory cells and axonal disruption in the subcortical white matter of the fetal brain can accompany chorioamnionitis induced by intra-amniotic administration of LPS, but cystic lesions do not occur. Thus, the effect on the fetal brain is milder than that reported from animal models of acute fetal/intrauterine infection.

Amniotic Fluid↗
PubMed2006

Variability of the initial phase of the ventilatory response to hypoxia in sleeping infants.

Most of the available data on the hypoxic ventilatory response (HVR) in infants has been obtained in quiet sleep (QS), and only one study has made repeated tests in the same infant. We aimed to gain a more complete knowledge of the maturation and consistency of the initial phase of the HVR by performing multiple tests in both QS and active sleep (AS) over the first 6 mo of life in term infants. Fifteen healthy term infants were studied with daytime polysomnography longitudinally at 2-5 wk, 2-3 mo, and 5-6 mo after birth. Each infant received multiple hypoxic (15% O2, balance N2) challenges (three or more) in both AS and QS. In AS, infants consistently aroused to hypoxia; however, in QS, infants both aroused and failed to arouse. The initial phase of the HVR varied considerably between infants with the changes in ventilation/kg [SD of inspired minute ventilation per kilogram of body weight (V(I)/kg)] being more variable during AS than QS at all three ages and overall decreasing with postnatal age in both sleep states. The variability between replicate V(I)/kg measurements was also significantly greater in AS compared with QS at 2-5 wk postnatal age. There was no evidence of habituation to repeated hypoxic tests in either sleep state. Our study has demonstrated that the initial phase of the HVR is variable both between and within term infants in both AS and QS, with responses being markedly more variable during AS, and becoming more consistent with increasing postnatal age. By performing only one test or by failing to account for arousal responses, previous studies may not have detected the natural variation of the infant HVR.

Age Factors↗
PubMed2006

Is antiretroviral therapy associated with symptom prevalence and burden?

Although distressing pain and other symptoms have been reported at all stages of HIV disease, studies have not taken account of the relative contribution of treatment side-effects and underlying disease. This study aimed to assess the prevalence of symptoms, their burden and the association with use of highly active antiretroviral therapy (HAART). Three hundred and forty-seven gay men with HIV disease completed an online survey, reporting data on age, CD4, viral load, year of diagnosis, HAART use, and the Memorial Symptom Assessment Scale Short Form (MSAS-SF).Those men currently receiving HAART (n=210, 56.6%) reported a higher number of symptoms than those without (14 versus 10.3, P=0.001). Fourteen physical symptoms were significantly more frequent among HAART users. Symptoms of psychological distress were the most common in both groups, ranging from 69.2% to 79.5%. Mean distress indices were higher for those on treatment with respect to both global (P=0.011) and physical (P=0.001) distress. In multivariate analysis, use of HAART was independently associated with number of physical symptoms (b=2.81, P=0.006), and physical distress score (b=2.45, P=0.017); both increasing with HAART use when controlling for age, year of diagnosis, CD4 and viral load. The high symptom prevalence, particularly psychological symptoms, is comparable with end-stage malignant and non-malignant diseases. Greater attention needs to be paid to the assessment and management of burdensome symptoms.

Adolescent↗
PubMed2005

Alveolar epithelial cell differentiation and surfactant protein expression after mild preterm birth in sheep.

As the transition to extrauterine life at birth alters the proportions of type I and II alveolar epithelial cells (AECs), our aim was to determine the effect of mild preterm birth on AECs and surfactant protein (SP) gene expression. Preterm lambs were born at approximately 133 d of gestational age (DGA); controls were born at term (approximately 147 DGA). Lungs were collected from preterm lambs at term-equivalent age (TEA; approximately 2 wk after preterm birth) and 6 wk post-TEA. Control lung tissue was collected from fetuses (at 132 DGA), as well as from lambs at approximately 6 h (normal term) and 2, 6, and 8 wk of postnatal age (PNA). In controls, the proportion of type I AECs decreased from 65.1 +/- 3.9% at term to 50.9 +/- 3.3%, while the proportion of type II AECs increased from 33.7 +/- 3.9% to 48.5 +/- 3.3% at 6 wk PNA. At 2 wk after preterm birth, the proportions of type I and II AECs were similar in preterm lambs compared to 132-d fetal levels and term controls but differed from control values at 2 wk PNA; differences between control and preterm lambs persisted at 8 wk PNA. At approximately 2 wk after preterm birth, SP-A and SP-B, but not SP-C, mRNA levels were significantly reduced in preterm lambs compared with term controls, but these differences did not persist at 2 and 6 wk PNA. We conclude that mild preterm birth alters the normal postnatal changes in type I and II cell proportions but does not severely affect SP gene expression.

Animals↗
PubMed2005

Postnatal development of ventilatory and arousal responses to hypoxia in human infants.

During the first year of life there is significant maturation of the hypoxic ventilatory response (HVR) in human infants. Compared with adults, healthy term infants have an immature HVR until at least 6 months of age. There are few studies in infants on the effects of sleep state on the HVR but these suggest that at early postnatal ages there is initially no sleep-state related difference; this is followed by a developmental trend towards the adult situation in which the response is depressed in REM sleep compared with NREM. Maternal cigarette smoking is a major risk factor for SIDS and the mechanism for this may involve a depressed HVR in the exposed infant; however studies are limited and the wide variation in cigarette consumption makes interpretation of results difficult. Arousal responses to hypoxia are of vital importance and a failure to arouse has been implicated in SIDS. Sleeping infants frequently fail to arouse in response to hypoxia in QS, whereas in AS they invariably arouse; furthermore arousal latency is longer in QS compared with AS. The oxygen saturation at which infants arouse is not different between sleep states, suggesting that desaturation is more rapid in AS. In QS younger infants arouse more readily than at older ages and arousal is depressed by maternal smoking. These findings suggest that depression of the arousal response to hypoxia in AS may have life-threatening consequences. Infants at increased risk for SIDS have been shown to have both depressed ventilatory and arousal responses to hypoxia, thus they may be at even greater risk.

Animals↗
PubMed2005

Prenatal hypoxia impairs memory function but does not result in overt structural alterations in the postnatal chick brain.

We showed previously that hypoxia in ovo impairs memory consolidation in the chick tested 2 days after hatching. Our present aim was to investigate whether we could detect any morphological effects of the same prenatal hypoxia. Hypoxia was induced by half-wrapping the egg with an impermeable membrane from either days 10-18 (W10-18 chicks) or days 14-18 (W14-18 chicks) of incubation (hatching approximately 21 days). Measurement of blood gases showed that reducing the surface area of the egg for gas exchange resulted in reduced pO2 and increased pCO2 2 days after wrapping. Although this hypoxia was sufficient to impair cognitive processing in the postnatal chick, our data suggest that it did not produce overt structural alterations or changes in the number of neurons, glutamine synthetase-immunoreactive cells or immunoreactivity to synaptophysin in the presynaptic vesicles in the multimodal integration (cortical) area compared to controls. Hence, we found no differences in the astrocyte to neuron ratio, synaptic density and/or vesicle number. Analysis of the ontogeny of astrocytes during the prenatal period of hypoxia showed them to be present at embryonic day 12, but not at the earlier ages examined. Although we found cognitive deficits in chicks from embryos made hypoxic during incubation, our regimen of prenatal hypoxia did not alter any of the parameters measured in the brains. This does not preclude the possibility that changes have occurred at the cellular or molecular levels or in specific neurotransmitter systems.

Animals↗
PubMed2005

An evaluation of a morphine public health programme for cancer and AIDS pain relief in Sub-Saharan Africa.

BACKGROUND: Despite growing HIV and cancer prevalence in Sub-Saharan Africa, and WHO advocacy for a public health approach to palliative care provision, opioid availability is severely limited. Uganda has achieved a morphine roll-out programme in partnership with the Ministry of Health. This study aimed to evaluate that programme by identifying challenges to implementation that may inform replication. METHODS: A multi-methods protocol appraised morphine regulation, storage, prescribing, and consumption in three phases: key informant interviews throughout the opioid supply chain, and direct observation and audit of clinical practice. RESULTS: Regulation had achieved its goal of preventing misuse and leakage from the supply chain. However, the Government felt that relaxation of regulation was now appropriate. Confusion and complexity in storage and authorization rules led to discontinuation of opioid pain management at the patient level and also wasted service time in trying to obtain supplies to which they were entitled. Continued neglect to prescribe among clinicians and public fear of opioids led to under prescribing, and clinical skills showed some evidence of need for improvement with respect to physical assessment and follow-up. CONCLUSION: The Ugandan programme offers a successful model for both advocacy and Governmental support in achieving opioid roll-out across health districts. Despite initial concerns, abuse of opioids has not been evident. Further work is required to ensure that available supplies of opioids are prescribed to those in need, and that clinical standards are met. However, the programme for roll-out has proved a useful model to expand opioid availability as the first step in improving patient care, and may prove a useful template for other Sub-Saharan African countries.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Positive end-expiratory pressure differentially alters pulmonary hemodynamics and oxygenation in ventilated, very premature lambs.

In mature lungs, elevated positive end-expiratory pressure (PEEP) reduces pulmonary blood flow (PBF) and increases pulmonary vascular resistance (PVR). However, the effect of PEEP on PBF in preterm infants with immature lungs and a patent ductus arteriosus is unknown. Fetal sheep were catheterized at 124 days of gestation (term approximately 147 days), and a flow probe was placed around the left pulmonary artery to measure PBF. At 127 days, lambs were delivered and ventilated from birth with a tidal volume of 5 ml/kg and 4-cmH(2)O PEEP; PEEP was changed to 0, 8, and 12 cmH(2)O in random order, returning to 4 cmH(2)O between each change. Increasing PEEP from 4 to 8 cmH(2)O and from 4 to 12 cmH(2)O decreased PBF by 20.5 and 41.0%, respectively, and caused corresponding changes in PVR; reducing PEEP from 4 to 0 cmH(2)O did not affect PBF. Despite decreasing PBF, increasing PEEP from 4 to 8 cmH(2)O and 12 cmH(2)O improved oxygenation of lambs. Increasing and decreasing PEEP from 4 cmH(2)O significantly changed the contour of the PBF waveform; at a PEEP of 12 cmH(2)O, end-diastolic flow was reduced by 82.8% and retrograde flow was reestablished. Although increasing PEEP improves oxygenation, it adversely affects PBF and PVR shortly after birth, alters the PBF waveform, and reestablishes retrograde flow during diastole.

Animals↗