Surfactant dysfunction after inhalation of nitric oxide.

To study whether nitric oxide (NO) affects surfactant function, 36 young rats inhaled one of the following humidified environments for 24 h: 1) air; 2) 95% O2; 3) air and 100 parts/million (ppm) NO; and 4) 95% O2 and 100 ppm NO. The treatments did not change the recovery of phospholipid from bronchoalveolar lavage (BAL). Exposure to NO of animals that breathed either air or 95% O2 increased the minimum surface tension of surfactant from BAL at low (1.5 mumol/ml), but not at high (4 mumol/ml), phosphatidylcholine concentration. After inhaled NO, the nonsedimentable protein of BAL decreased the surface activity of surfactant (1 mumol phosphatidylcholine/ml) more than the protein from the controls. NO treatment of animals that breathed either air or 95% O2 affected neither the quantity nor the molecular weight distribution of nonsedimentable protein. Hyperoxia increased the amount of the nonsedimentable protein, whereas NO increased the iron saturation of transferrin. The surfactant fraction and the nonsedimentable protein from BAL were separately exposed to 80 ppm NO in vitro. NO exposure had no effect on the surface activity of surfactant fraction. NO exposure of nonsedimentable protein from the control animals (no NO) increased the inhibition of the surface activity and changed the adsorption spectrum of the protein, suggesting conversion of hemoglobin to methemoglobin. Nonsedimentable protein from NO-exposed animals contained methemoglobin. We propose that surfactant dysfunction caused by inhaled NO is in part due to alteration of protein(s) in epithelial lining fluid that in turn inactivates surfactant.

Results of EDAP lithotriptor treatment of kidney stones in our first fifty patients.

We report the results of the treatment of the first 50 patients with the EDAP lithotriptor at our center. The EDAP is a second generation lithotriptor that employs ultrasound imaging and piezo-electric energy stone fragmentation. Seventy-six percent of patients had kidney stones completely eliminated or residual no greater than 3 mL. Fourteen percent of patients had residual fragments which may require second treatment. Five stones showed no improvement, and 2 stones could not be imaged. Only 2 patients required anesthesia. One patient required hospitalization prior to treatment. The rest were treated as outpatients. This preliminary FDA-investigative study limited our protocol to stones of 0.5 cm to 2.5 cm within the kidney or proximal ureter. Since particles passed were so small, "steinstrasse phenomenon" (distal ureteral obstruction by stone fragments) was not encountered and routine stent placement was obviated. There were no major complications.

Echocardiographic evidence of improved hemodynamics during inhaled nitric oxide therapy for persistent pulmonary hypertension of the newborn.

To evaluate the cardiovascular effects of inhaled nitric oxide (NO) on the systemic and pulmonary circulations, 25 consecutive infants with severe persistent pulmonary hypertension of the newborn (PPHN) underwent serial echocardiographic evaluations before and during inhaled NO therapy. Estimation of the systolic pulmonary artery pressure (SPAP) was derived from measurement of a tricuspid regurgitant jet using Bernoulli's equation. We also derived a pulmonary/systemic pressure ratio to evaluate overall cardiopulmonary effects. Paired measurements of estimated SPAP decreased from 62.0 +/- 3.8 mmHg to 44.7 +/- 4.3 mmHg (p < 0.01) during inhaled NO therapy. The pulmonary/systemic pressure ratio decreased from 0.98 +/- 0.06 to 0.59 +/- 0.04 during NO therapy (p < 0.01), indicating a significant decline in the vascular resistance between the two circulations. These changes also correlated with changes in the extrapulmonary shunt patterns at the ductus arteriosus and foramen ovale seen during inhaled NO therapy. The decreased right-to-left shunting was accompanied by a parallel (64%) improvement in systemic oxygenation, with the alveolar-arterial oxygen gradient (A-a DO2) falling from 591 +/- 14 mmHg to 380 +/- 33 mmHg (p < 0.01). We found echocardiography to be a useful clinical tool for evaluating and monitoring pulmonary artery pressure in infants with PPHN. Measurement of the SPAP and the pulmonary/systemic pressure ratio gave a quantitative estimation of the severity of PPHN, and the extrapulmonary shunt flow patterns at the ductus arteriosus and foramen ovale gave qualitative estimates of its severity. Inhaled NO increased pulmonary blood flow and oxygenation and improved the systemic cardiopulmonary hemodynamics in this group of infants.

Variable oxygenation response to inhaled nitric oxide in severe persistent pulmonary hypertension of the newborn.

The causes of variable responsiveness to inhaled nitric oxide (NO) in Persistent Pulmonary Hypertension of the Newborn (PPHN) are unknown. The changes in the severity of respiratory failure after the onset of inhaled NO (maximal dose 20 ppm) were studied in 13 consecutive neonates with severe PPHN. Response was defined as a sustained decrease of alveolar-arterial oxygen gradient (AaDO2) by > 20%, or a decrease in oxygenation index (OI) by > 40%. Six neonates had a rapid response within 30 min, three had an intermediate response within 8 h, and three had a delayed response within 12 h after the onset of NO. Three infants with birth asphyxia responded rapidly to inhaled NO. One infant with sepsis did not respond, and two with suspected sepsis had a delayed response. The infants with Meconium Aspiration Syndrome and idiopathic PPHN had a variable response time. Twelve neonates required 4 to 14 days of mechanical ventilation and survived. Infants with PPHN may benefit from a trial of inhaled NO therapy that exceeds 30 min. The variability of the response time to inhaled NO is likely to be multifactorial and dependent on the disease process associated with PPHN.

Pulmonary toxicity associated with nitric oxide in term infants with severe respiratory failure.

We prospectively analyzed airway specimens from 24 newborn infants. Inhaled nitric oxide (< or = 20 ppm for 1 to 4 days to 12 infants) did not affect the concentrations of the lipid peroxidation product, the surface activity, or the cytokines (interleukin-1, granulocyte-macrophage colony-stimulating factor, interleukin-1 receptor antagonist). Nitrotyrosine was detected after 10 days of life in the two infants requiring prolonged ventilation, suggesting toxicity of endogenous nitric oxide.

Cerebral lactate metabolism in near-term fetal sheep.

The present study was designed to see if lactate can cross the blood-brain barrier of the near-term fetal sheep and replace glucose as an oxidative substrate during normoglycemia and acute insulin-induced hypoglycemia. Cerebral uptake of glucose, oxygen, lactate, and [14C]lactate as well as cerebral production of 14CO2 were measured under three conditions: 1) normoglycemia-normolactemia, 2) acute hypoglycemia-normolactemia, and 3) hypoglycemia-steady-state hyperlactemia. Although uptake of tracer [14C]lactate was consistent, there was no net uptake of unlabeled lactate during either normoglycemia or hypoglycemia. When arterial lactate concentration was raised from 2.2 +/- 0.5 to 3.3 +/- 0.4 (SE) mM by sodium lactate infusion, however, lactate was taken up. Comparison of cerebral [14C]lactate uptake with 14CO2 production indicated that the principal metabolic fate of lactate is oxidation. At increased concentrations, exogenous lactate accounted for approximately 7% of cerebral oxygen consumption. This study demonstrates that lactate crosses the blood-brain barrier of the near-term fetal sheep, is oxidized, and at elevated concentrations can partially replace glucose as an oxidative substrate during acute hypoglycemia.