Persistent pulmonary hypertension of the newborn causes systemic arterial hypoxemia because increased vascular resistance and right-to-left shunting deoxygenated blood. Inhaled nitric oxide decreases in newborns. We studied whether inhaled severe infants with persistent hypertension.

Congenital heart lesions may be complicated by pulmonary arterial smooth muscle hyperplasia, hypertrophy, and hypertension. We assessed whether inhaling low levels of nitric oxide (NO), an endothelium-derived relaxing factor, would produce selective vasodilation in pediatric patients with congenital disease also compared the vasodilator potencies inhaled NO oxygen these patients.In 10 sequentially presenting, spontaneously breathing patients, we determined 20-80 ppm volume at inspired...

Nitric oxide (NO) inhalation selectively decreases pulmonary artery hypertension and improves arterial oxygenation in patients with the adult respiratory distress syndrome (ARDS). In this study of severe ARDS, we sought to determine effect inhaled NO dose time on pressure oxygen exchange which ARDS are most likely show response.Thirteen (hospital mortality 67%) 0-40 parts per million (ppm) NO. Seven these continued breathe 2-20 ppm for 2-27 days.Inhaling 5-40 decreased mean a dose-related...

We determined whether inhaling low levels of nitric oxide (NO) gas could selectively reverse hypoxic pulmonary vasoconstriction in the near-term newborn lamb and vasodilation would be attenuated by respiratory acidosis. To examine mechanism air NO-induced soon after birth, we measured plasma lung cGMP newly ventilated fetal lamb. Breathing at FIO2 0.10 nearly doubled vascular resistance index lambs decreased blood flow primarily reducing left-to-right through ductus arteriosus. Inhaling 20...

Studies in vitro have underestimated the importance of cGMP-dependent protein kinase (PKG) modulation vascular smooth muscle cell (SMC) proliferation and apoptosis vivo. This is attributable, part, to a rapid decline PKG levels as SMC are passaged culture. We used recombinant adenovirus encoding (Ad.PKG) augment activity cultured rat pulmonary artery (RPaSMC). Incubation Ad.PKG-infected RPaSMC (multiplicity infection = 200) with 8-Br-cGMP decreased serum-stimulated DNA synthesis by 85% at...

Pulmonary injury is associated with the disruption of alveologenesis in developing lung and causes bronchopulmonary dysplasia (BPD) prematurely born infants. Transforming growth factor (TGF)-beta an important regulator cellular differentiation early development, its levels are increased newborn injury. Although overexpression TGF-beta lungs animals pathological features that consistent BPD, role endogenous inhibition terminal stage development incompletely understood. In this investigation,...

It is known that 5-lipoxygenase and its product, leukotriene B4 (LTB4), are highly expressed in several human pathologies, including atherosclerotic plaque. LTB(4) signals primarily through high-affinity G protein-coupled receptor BLT1, which on specific leukocyte subsets. BLT1 expression function other atheroma-associated cell types unknown.To directly assess the role of LTB4-BLT1 pathway atherogenesis, we bred BLT1(-/-) mice into atherosclerosis-susceptible apoE(-/-) strain....

Liver fibrosis plays a critical role in the evolution of most chronic liver diseases and is characterized by buildup extracellular matrix, which can progress to cirrhosis, hepatocellular carcinoma, failure, or death. Now, there are no noninvasive methods available accurately assess disease activity (fibrogenesis) sensitively detect early onset response treatment. Here, we hypothesized that allysine aldehyde (Lys Ald ) pairs formed collagen oxidation during active could be target for...

Abstract Breathing low oxygen levels for several weeks produces progressive pulmonary artery hypertension and smooth muscle hypertrophy hyperplasia in many species. Because nitric oxide (NO) is an important regulator of vascular tone, we examined whether the continuous inhalation NO gas would attenuate arterial structural changes hypoxic rat pups. Nine-day-old pups their mothers continuously breathed at F io 2 0.21 or 0.10 with without adding 20 ppm (by volume) weeks. Lung tissue was...

Abstract Systemic and local intravascular NO administration inhibits neointimal formation after vascular injury in animal models. appears to attenuate smooth muscle proliferation both directly indirectly by preventing the release of growth factors. Inhalation low concentrations dilates pulmonary but does not cause systemic vasodilatation. Recently, inhalation was found inhibit platelet function vivo. We studied effects on balloon-induced adult rat carotid artery. Beginning 60 minutes before...

The placenta is an organ of embryonic origin that supports the growing fetus by facilitating transfer nutrients from mother. It not well understood how allogeneic thrives and avoids immune rejection in environment where only trophoblastic fetal capillary basement membranes separate maternal circulations. Reports vertical transmission cancer are exceptionally rare, although cells do reach fetus1,2 occurs nearly 1 1000 pregnant women.3–5 Malignant melanoma best known example a can metastasize...

A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they estimated to be between 24 and 30 weeks' gestation, weighed 750 1250 g, intubated stabilized within 15 minutes after birth. total 160 infants treated (79 surfactant, 81 placebo) 4 37...

Gram-negative bacterial sepsis commonly causes organ dysfunction and death in humans. Although circulating toxins trigger inflammation sepsis, little is known about the composition of products released into blood during or contribution various components to pathogenesis sepsis. We have shown that diverse bacteria release peptidoglycan-associated lipoprotein (PAL) serum. The present studies explored PAL tested hypothesis contributes virulence Released was detected 94% mice following cecal...

Disordered extracellular matrix production is a feature of bronchopulmonary dysplasia (BPD). The basis this phenomenon not understood.To assess lysyl oxidase expression and activity in the injured developing lungs newborn mice prematurely born infants with BPD or at risk for BPD.Pulmonary elastin gene protein were assessed breathing 21 85% oxygen, patients who died BPD, control patients. Signaling by transforming growth factor (TGF-beta) was preemptively blocked exposed to hyperoxia using...

Integrin-linked kinase (ILK) is located at focal adhesions and links the extracellular matrix (ECM) to actin cytoskeleton via β1- β3-integrins. ILK plays a role in activation of kinases including protein B/Akt glycogen synthase 3β regulates cell proliferation, motility, survival.To determine function vascular smooth muscle cells (SMCs) vivo.SM22Cre(+)Ilk(Fl/Fl) conditional mutant mice were generated which Ilk gene was selectively ablated SMCs. SM22Cre(+)Ilk(Fl/Fl) survive birth but die...

Summary Background Electrical C ardiometry ™ ( EC ) estimates cardiac parameters by measuring changes in thoracic electrical bioimpedance during the cycle. The ICON ® , using four electrocardiogram electrodes (EKG), maximum rate of change impedance to peak aortic blood acceleration (based on premise that red cells from random orientation diastole (high impedance) an aligned state systole (low impedance)). Objective To determine whether continuous output CO data provide additional information...

Respiratory rate (RR) is a critical vital sign used to assess pulmonary function. Currently, RR estimating instrumentation specialized and bulky, therefore unsuitable for remote health monitoring. Previously, was estimated using proprietary software that extract surface electrocardiogram (ECG) waveform features obtained at several thoracic locations. However, developing non-proprietary method uses minimal ECG leads, generally available from mobile cardiac monitors highly desirable. Here, we...

Abstract —Vascular injury causes the muscularization of peripheral pulmonary arteries, which is more pronounced in infant than adult lung. Although inhaled NO gas attenuates artery remodeling hypoxic rats, whether or not it protects lung by mitigating vasoconstriction unknown. This investigation tested decreases injured arteries rat pups modulating vascular tone. One week after monocrotaline administration, percentage muscularized pup was increased >3-fold. Nevertheless, exposure did...

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Nitric oxide (NO) regulates lung development through incompletely understood mechanisms. NO controls pulmonary vascular smooth muscle cell (SMC) differentiation largely stimulating soluble guanylate cyclase (sGC) to produce cGMP and increase cGMP-mediated signaling. To examine the role of sGC in regulating development, we tested whether decreased activity reduces alveolarization normal injured newborn lung. For these studies, mouse pups with gene-targeted sGC-α1 subunit truncation were used...

The intracellular signaling mechanisms through which TGF-β regulates pulmonary development are incompletely understood. Canonical involves Smad2/3 phosphorylation, Smad2/3·Smad4 complex formation and nuclear localization, gene regulation. Here, we show that physiologically relevant TGF-β1 levels also stimulate Smad1/5 is typically a mediator of bone morphogenetic protein (BMP) signaling, in mouse pup artery smooth muscle cells (mPASMC) lung fibroblasts other interstitial cell lines. This...

Aberrant remodelling of the extracellular matrix in developing lung may underlie arrested alveolarisation associated with bronchopulmonary dysplasia (BPD). Transglutaminases are regulators remodelling. Therefore, expression and activity transglutaminases were assessed lungs from human neonates BPD a rodent model BPD. Transglutaminase localisation by RT-PCR, immunoblotting, assay immunohistochemical analyses mouse tissues. regulation transforming growth factor (TGF)-β was investigated cells...