Effects of inhaled nitric oxide on gas exchange and acute lung injury in premature lambs with moderate hyaline membrane disease.

OBJECTIVE: The purpose of this study was to examine whether inhaled nitric oxide (iNO) may change lung injury in moderate hyaline membrane disease (HMD). METHODS: Fifteen moderately premature lambs (128 days gestation, term=147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n=7) from the onset of ventilation or control (n=8). Except for inhaled NO, treatments were intentionally similar to those applied in clinical situations. After porcine surfactant administration (Curosurf, 100 mg/kg), mechanical ventilator settings were modified during the course of the study to maintain PaCO(2) between 40 and 50 mmHg and post-ductal SpO(2) between 90 and 95%. The main studied parameters were gas exchanges parameters, respiratory mechanics (static compliance and functional residual capacity) and pulmonary vascular permeability and/or filtration rate indices. RESULTS: We found that 20 ppm of inhaled NO for 5 h significantly reduce ventilatory and oxygen requirements, but only during the first hour of mechanical ventilation. No increase in extravascular lung water content (5.41+/-0.96 vs. 5.46+/-1.09 ml/g bloodless dry lung in the control group and in the NO group, respectively) and no impairment of the respiratory mechanics could be found in the NO-treated group. However, inhaled NO increased the albumin lung leak index in this model (6.09+/-1.51 in the NO-treated group vs. 4.08+/-1.93 in the control group; P<0.05). CONCLUSIONS: Our results do not therefore support a detrimental effect of short-term exposure to low doses of NO inhalation in moderate HMD. However, it may induce an increase in lung vascular protein leakage. The pathophysiological consequences of this finding remain to be elucidated.

Adsorption and release of insulin-like growth factor-I on porous tricalcium phosphate implant.

In order to develop bone substitutes, the design of biomaterials like calcium phosphate ceramic loaded with bone growth factor are of great interest. However, it is necessary to control the amount of growth factor adsorbed onto ceramics and the kinetics of its release. Radiolabeling of insulin-like growth factor-I (IGF-I) with 125-iodine ([(125)I]-IGF-I) and its adsorption onto porous tricalcium phosphate (TCP) cylinders enabled us to establish the time-adsorption and time-release curves using various concentrations of IGF-I. The adsorption curve increased rapidly and then flattened out at 72 h; 90% of the maximum was already reached at 24 h; and 20% of the adsorbed IGF-I was released in water within 4 days. In human serum the release was faster at 82% within 4 days. In vivo evaluation on an animal model was then performed. Rabbits' bilateral femoral cylindrical bone defects were filled with the TCP cylinders, which were either carrying IGF-I or implanted alone as a control in each rabbit. Bone turnover and ceramic resorption were stimulated by IGF-I loaded TCP according to standard radiography, dual-energy X-ray absorptiometry, histology, and histomorphometry.

Inhaled NO preadministration modulates local and remote ischemia-reperfusion organ injury in a rat model.

Inhaled nitric oxide (iNO) has been shown to have a protective effect in lung ischemia-reperfusion (I/R)-induced injuries. We studied the role of iNO (10 parts/million for 4 h) administered before I/R. In an isolated perfused lung preparation, iNO decreased the extravascular albumin accumulation from 2,059 +/- 522 to 615 +/- 105 microl and prevented the increase in lung wet-to-dry weight ratio. To study the mechanisms of this prevention, we evaluated the role of nitric oxide (NO) transport and lung exposure with matched experiments by using either lungs or blood of animals exposed to iNO and blood or lungs of naive animals. iNO-exposed blood with naive lungs did not limit the extravascular albumin accumulation (2,561 +/- 397 microl), but iNO-exposed lungs showed a leak not significantly different from the group in which both lungs and blood were iNO exposed (855 +/- 224 vs. 615 +/- 105 microl). An improvement in heart I/R left ventricular developed pressure in the animals exposed to iNO showed that blood-transported NO was, however, sufficient to trigger remote organ endothelium and reduce the consequences of a delayed injury. In conclusion, preventive iNO reduces the consequences of lung I/R injuries by a mechanism based on tissue or endothelium triggering.

Combined effects of inhaled nitric oxide and hyperoxia on pulmonary vascular permeability and lung mechanics.

OBJECTIVE: To determine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in an in vivo model. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: University experimental pharmacology laboratory. SUBJECTS: Mechanically ventilated newborn piglets, 1 to 2 days old, exposed to 100% oxygen for 76 hrs. INTERVENTIONS: The piglets were randomly assigned either to a treatment group receiving 20 ppm inhaled NO from the onset of ventilation (n = 5) or to a control group (n = 6) receiving no treatment. MEASUREMENTS AND MAIN RESULTS: The main variables studied were gas exchange (PaO2/F(IO2) ratio, lung diffusing capacity), respiratory mechanics (static compliance of the respiratory system, stat, quasi-static hysteresis area, functional residual capacity), and pulmonary vascular permeability assessed by simultaneous intravenous administration of iodine-125-labeled albumin and chromium-51-labeled red blood cells. Extravascular albumin space of the lung and dry lung weight were significantly higher in the NO group vs. the control group (albumin space, 1.08+/-0.16 vs. 0.70+/-0.26 [SD] mL/kg body weight [p < .05]; dry lung weight, 3.20+/-0.34 vs. 2.66+/-0.14 g/kg body weight [p < .05]). Moreover, the hysteresis area was higher from 24 hrs of NO exposure. Conversely, NO inhalation altered neither the extravascular lung water content (12.98+/-2.79 mL/kg body weight in the NO group vs. 12.18+/-2.26 mL/kg body weight in the control group [not significant]) nor the main respiratory mechanical variables (static compliance, functional residual capacity) and gas exchange (lung diffusing capacity, PaO2/F(IO2) ratio). CONCLUSION: These results do not support the hypothesis that NO inhalation combined with hyperoxia can alter the main lung-function variables in neonates. However, it may induce an increase in lung vascular protein leakage. The pathophysiologic consequences of this finding remain to be elucidated.

Fluorescein-labeled dextran concentration is increased in BAL fluid after ANTU-induced edema in rats.

Several methodologies have been developed to assess alveolocapillary membrane permeability in acute lung injury. The purpose of this study was to determine the reliability of FITC-dextran compared with radioactive tracers to assess lung permeability alterations. After intraperitoneal administration of alpha-naphthylthiourea (ANTU, 50 mg/kg) or DMSO-ANTU vehicle, the animals were euthanized and their lungs were studied in an isolated-lung preparation. FITC-dextran or radiolabeled tracers were added to the perfusate. At 2 h the bronchoalveolar lavage (BAL) fluid from the ANTU group showed a significantly greater amount of fluorescence in the supernatant after centrifugation of BAL fluid compared with the DMSO group. Consistent results were observed with the radioactive tracers: there was an increase in extravascular albumin space and extravascular lung water compared with the control group. No cleavage of the FITC from the dextran molecule was evident by chromatography comparing samples recovered from the BAL fluid to the pure FITC-dextran molecule. In conclusion, measurement of FITC-dextran in the supernatant of BAL fluid after intravascular administration is a reliable method of assessing lung permeability changes in vivo and ex vivo.

Pulmonary stress injury within physiological ranges of airway and vascular pressures.

PURPOSE: The aim of this study was to assess the respective role of a small elevation in pulmonary capillary pressure, airway pressure, or both on alveolar capillary barrier permeability in an isolated perfused rat lung model. MATERIALS AND METHODS: Four groups were studied with low or high airway pressure (LA: 10 mL/kg (tidal volume); HA: 20 mL/kg), low or high pulmonary artery pressure (LP: 9 mm Hg; HP: 12 mm Hg): LALP, HALP, LAHP, and HAHP. The lungs were ventilated and perfused ex vivo for 30 minutes. Quantification of fluorescein isothiocyanate-labeled (FITC) dextran in bronchoalveolar lavage (BAL) fluid and radiolabeled tracers assessed alveolar capillary barrier permeability. RESULTS: BALF FITC-dextran was similar in the three groups with either one or two low-pressure parameters (LALP, LAHP, HALP), but high amounts were found in the HAHP group (375.2 x 10(-6) mg/mL v, respectively, 21.4, 26.2, and 30 x 10(-6) mg/mL, P = .0001). These results were consistent with the albumin space and extravascular lung water: higher values only in the HAHP group statistically different from the other groups (P < .002). Interalveolar pore examined with scanning electron microscopy showed an increase in diameters between LALP and HAHP (P < .0001). CONCLUSIONS: We can conclude that elevation of either the pulmonary artery pressure from 8 to 11 mm Hg or the alveolar pressure from 10 to 15 mm Hg alone does not change the permeability of the alveolar capillary membrane; however, there is an additive effect of these pressures.

Regional cerebral blood flow imaging: a quantitative comparison of 99mTc-bicisate with 133Xe using single photon emission computed tomography.

The aim of this study was to compare 99mTc-bicisate with 133Xe inhalation in regional CBF (rCBF) imaging. Five healthy volunteers and five patients were imaged with both techniques. Regional standardized values (SVs) of 99mTc-bicisate, uptake indexes (UIs), and asymmetry indexes (AIs) were compared quantitatively with, respectively, rCBF, flow indexes (FIs), and AIs. Areas with highest rCBF (sylvian and thalamic areas) appeared to be underestimated with 99mTc-bicisate, but significant correlations were found between SV and rCBF (n = 140, r = 0.468, p < 0.01) and for the 10 subjects between UI and FI and between AIs (p < 0.0001). There are therefore distinct regional differences in the cerebral distinction of 99mTc-bicisate and CBF, particularly in the thalamus and the temporal cortex. It is probable but not yet proved that an underestimation of high flow rates occurs with bicisate.

Assessment of the reproducibility of nocturnal growth hormone secretion.

The reproducibility of measurements of nocturnal spontaneous secretion of growth hormone (GH) was assessed. The study population consisted of 15 short children with a variety of pathological conditions. Blood samples were taken every 20 min from each subject during sleep on two consecutive nights. The analysis of variance of matched series indicated a global reproducibility, but also demonstrated significant individual variabilities (with-in-subject effect) of both peak amplitude (p = 0.05) and mean concentration (p = 0.02). We did not find any link between the variation of the GH parameters and the variations of the clinical sleep score in 11 patients.

[Tomographical use of Tc hexamethylpropylene amine-oxime. First experience (78 studies)]. / Utilisation tomographique de l'hexaméthylpropylène amine-oxyme Tc. Première expérience (78 études).

A new radiotracer of cerebral perfusion, 99mTc-labelled hexamethylpropylene amine-oxime, has been tried in 78 subjects: 6 controls and 72 patients. Qualitatively, the distribution of this tracer in healthy subjects was very much the same as that obtained with a reference method using 133xenon inhalation. Quantitatively, there was no correlation between the real blood flow rate and the normalized cerebral uptake rate. On the other hand, the asymmetry indices obtained in controls (but also in 16 patients) correlated very closely with those obtained with 133xenon. Our first results in acute ischaemic diseases as well as in the evaluation of vasospasm or Alzheimer-like presenile dementia point to wide fields of application for the new compound. Unlike its predecessors, it is always available and will probably be used, without any logistic investment, with the standard equipment of all Nuclear medicine departments.