Meconium aspiration induces a concentration-dependent pulmonary hypertensive response in newborn piglets

To investigate the effects of aspirating different meconium concentrations on the pulmonary circulation in 10- to 12-day-old piglets, 30 catheterized animals were studied. The piglets received an intratracheal bolus of 3 ml/kg of a mixture of human meconium in saline with concentrations of 20 mg/ml (light, n = 7), 40 mg/ml (moderate, n = 6), or 65 mg/ml (thick, n = 10) meconium in saline. Control piglets (n = 7) received 3 ml/kg of intratracheal saline. Pulmonary and systemic pressures were measured and vascular resistances calculated at baseline and serially for 4 hours after instillation. Four of the piglets died early and were excluded from the study. In addition, 23 samples of human meconium-stained amniotic fluid were collected at delivery for determination of their meconium concentration. After an initial rise in pulmonary artery pressure and vascular resistance after meconium and saline instillation, pulmonary artery pressure and resistance increased progressively and concentration-dependently in the meconium groups, but returned to baseline in the control group. The saline and meconium-induced initial increases, and the subsequent meconium-stimulated progressive rise in vascular resistance occurred mainly in the postarterial segment. There were no significant changes in systemic hemodynamics. Mean airway pressure increased and oxygenation deteriorated after meconium instillation. The impairment of oxygenation depended on the meconium concentration in the instilled bolus and persisted throughout the study after moderate and thick meconium instillation. Similarly, the intrapulmonary shunt fraction increased initially and remained elevated in the moderate and thick meconium groups. Meconium concentrations in the human amniotic fluid samples were in the same range as concentrations used in the present experimental study. These results indicate that aspirated meconium at concentrations found in light to moderate meconium-stained human amniotic fluid has significant effects on pulmonary hemodynamic and oxygenation in newborn piglets. Pediatr. Pulmonol. 1998; 25:107–113. © 1998 Wiley-Liss, Inc.     

Effects of meconium aspiration in isolated perfused rat lungs

Our objective was to study meconium-induced lung injury in isolated perfused rat lungs exposed to anoxia. Our working hypothesis was that meconium-induced lung injury is independent of preexisting hypoxia, and that hypoxia will increase severity of lung injury observed after meconium aspiration. We compared five different groups of animals (n = 5) for pulmonary arterial pressure (PAP), weight lung changes, and TNFalpha expression. Group I had lungs instilled with 4 ml of normal saline. Group II had lungs exposed to 5 min of anoxia. Group III had lungs instilled with 4 ml of 30% filtered human meconium. Group IV had lungs exposed to 5 min of anoxia and then instilled with 4 ml of 30% filtered human meconium. Group V had lungs instilled with 4 ml of 30% unfiltered human meconium. Our subjects were adult Sprague-Dawley rats. The isolated rat lung model was prepared according to Levey and Gast (J Appl Physiol 1966;21:313-316). Lungs were ventilated with room air. Anoxia was caused by the use of N(2). The pulmonary artery was cannulated, and pulmonary arterial pressure and lung weight were measured. Lung weight and pulmonary arterial pressure were monitored for 120 min, and TNFalpha levels were measured in effluent at 15, 30, 60, and 120 min. Experiments were done at the Michael Reese Hospital (Chicago, IL). At the end of the experiment, PAP reached its highest values in group V (10.0 +/- 1.7 mmHg). Final PAPs in groups I-IV were: 4.85 +/- 0.3, 4.99 +/- 0.4, 5.93 +/- 0.3, and 7.25 +/- 0.51 mmHg, respectively). Lung wet weight increased significantly only in groups IV and V vs. group I; at 120 min, they were: 0.96 +/- 0.3 g, P < 0.01, and 1.5 g +/- 0.2 g, P < 0.01, respectively. TNFalpha levels did not change significantly over time in group I. TNFalpha is a marker as well as proprietor of pulmonary inflammatory response. TNFalpha reached its highest levels in groups IV and V: 595 and 753 pg/ml at 120 min, respectively. In conclusion, a short episode of anoxia prior to meconium aspiration may increase lung sensitivity to meconium-induced lung injury. This effect may be moderated by the TNFalpha present in the pulmonary circulation.     

Effects of exogenous surfactant on gas exchange and compliance in rabbits after meconium aspiration.

Success in using adjunctive surfactant therapy for meconium aspiration has been inconsistent. We tested the hypothesis that the ability of exogenous surfactant to improve gas exchange and pulmonary compliance after meconium aspiration is related to the method of surfactant administration. In anesthetized rabbits (2.4 +/- 0.16 kg body weight), an endotracheal tube (ETT) was placed in the lower trachea, and the lungs were ventilated mechanically. After a control period, filtered meconium (3-5 mL/kg) was instilled through the ETT. Group 1 (n = 5) was not given surfactant. Thirty minutes after meconium instillation, group 2 (n = 5) was given a bolus of bovine surfactant (Beractant, 4 mL/kg) through the ETT, and group 3 (n = 5) was given an infusion of Beractant (4 mL/kg for 1 hr) through the side-port of the ETT. Thirty minutes after meconium instillation, tracheal pressure increased by 8 +/- 1 cm H(2)O (mean +/- SEM), dynamic compliance decreased by 0.36 +/- 0.07 mL/cm H(2)O/kg, arterial PO(2) (PaO(2)) decreased by 49 +/- 6.0 mmHg, arterial PCO(2) (PaCO(2)) increased by 12 +/- 2.4 mmHg, and arterial pH (pHa) decreased by 0.09 +/- 0.02. After 3 hr of exposure to meconium, tracheal pressure was significantly (P < 0.001) lower in group 3 compared to groups 1 or 2. PaO(2) remained below baseline in all groups. Group 3 had a significantly (P = 0.001) higher dynamic compliance than groups 1 or 2. Likewise, static compliance was higher for group 3 compared to groups 1 or 2, with the greatest difference at low lung volume. Mean arterial blood pressure, pulse rate, PaCO(2), and pHa were not significantly different between groups. These results suggest that continuous infusion of exogenous surfactant is more effective than bolus administration in improving pulmonary function after meconium aspiration.     

Inhaled nitric oxide combined with prostacyclin and adrenomedullin in acute respiratory failure with pulmonary hypertension in piglets

Our aim was to evaluate if the combined inhalation of both nitric oxide (iNO) and aerosolized prostacyclin or iNO and adrenomedullin (ADM) is more effective in lowering pulmonary arterial pressure (PAP) and improving oxygenation than nitric oxide alone in an animal model with pulmonary hypertension (PH). Moreover, we studied the effect on pulmonary mechanics, surfactant activity, and pulmonary oxidative stress of the different treatments. Twenty-eight piglets with acute lung injury induced by lung lavages with saline were randomized to receive nitric oxide, nitric oxide plus prostacyclin, nitric oxide plus ADM or saline, after. Dynamic compliance, tidal volume, and airway resistance were measured. Lung tissue oxidation was evaluated by measuring total hydroperoxide and advanced oxidation protein products in bronchial aspirate samples. Surface surfactant activity was studied using Capillary Surfactometer. Inhaled nitric oxide combined with prostacyclin or ADM was more effective than nitric oxide alone in lowering PAP and improving oxygenation. Nitric oxide alone or combined increased lung compliance and tidal volume, and decreased airway resistance. No effects on surfactant surface activity and lung tissue oxidation were observed. The treatment with nitric oxide alone or combined with prostacyclin or ADM were effective in decreasing mean PAP and improving oxygenation in a piglet model of PH. However, nitric oxide plus prostacyclin and nitric oxide plus ADM were more effective than nitric oxide alone. The combination of aerosolized prostacyclin and ADM with nitric oxide might have a role in the treatment of infants with PH refractory to nitric oxide alone.     

Effects of inhibition of nitric oxide formation on the regulation of coronary blood flow in anesthetized dogs

In 11 open-chest dogs with a flowmeter on the left circumflex artery, L-NMMA, a selective inhibitor of nitric oxide-formation, was subselectively infused into the left circumflex artery at a rate of 2.5mg/ml (ml/min) to avoid systemic hemodynamic effects. The coronary blood flow at normal arterial blood pressure was similar prior to and during L-NMMA infusion. However, when the arterial blood pressure was raised by inflating a balloon in the descending aorta, the nitric oxide suppression induced a dramatic increase in coronary vascular resistance by almost 40% compared to control conditions without L-NMMA infusion at identically elevated arterial blood pressure. L-NMMA induced a significant downward shift and flattening of the pressure-flow relation over a pressure range from 60–150 mmHg. Peak hyperemic coronary flow after 20-s transient coronary occlusion was similar prior to and during L-NMMA infusion, but the duration of the hyperemic flow response was significantly shortened during L-NMMA infusion indicating exaggerated constriction after hyperemic stimulus. The EDRF/nitric oxide-system plays an important role for the regulation of coronary blood flow by counteracting autoregulatory constrictor responses to increased driving pressure and shear stress in the intact canine circulation.Supported in part by grant 1 RO1 HL-40865 from the National Heart, Lung, and Blood Institute. U.S. is the recipient of research grant So 241/1-1 from the Deutsche Forschungsgemeinschaft     

Meconium aspiration induces ARDS-like pulmonary response in lungs of ten-week-old pigs

To investigate whether aspiration of meconium induces a hemodynamic and histologic pulmonary response similar to that frequently seen in experimental acute respiratory distress syndrome, twelve 10-week-old pigs with postnatally adapted lungs were studied. Six 10-week-old pigs received 3 ml/kg 20% human meconium via the endotracheal tube. Six control pigs of the same age were given sterile saline. Ventilator settings were adjusted to keep PaO₂ above 8 kPa and PaCO₂ below 5 kPa. The pulmonary hemodynamic response to aspiration consisted of two separate hypertensive components. An initial peak in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) was followed by a progressive increase in PAP and PVR in the meconium group, whereas in the saline group these parameters returned to baseline levels. The distribution of PVR, determined by pulmonary artery occlusion, was characterized by an increase in the postarterial resistance immediately after meconium aspiration and a progressive increase in both arterial and postarterial resistances during the later phase. On histological examination, marked neutrophil sequestration was seen in the meconium lungs. In addition, lung edema formation was significantly enhanced in the meconium group, as shown by an increased lung wet/dry weight ratio. Thus, meconium aspiration resulted in a biphasic pulmonary pressor response and severe pulmonary inflammation. This response resembled that of models of experimental acute respiratory distress syndrome following diverse types of precipitating insults; this suggests that similar pathophysiologic mechanisms are elicited and cause similar pulmonary dysfunction following different forms of lung injury. Pediatr. Pulmonol. 1997; 23:205–211 © 1997 Wiley-Liss, Inc.     

Bronchoalveolar lavage versus bolus administration of lucinactant, a synthetic surfactant in meconium aspiration in newborn lambs

This study was designed to study effects of lung lavage versus the classical bolus instillation with a peptide‐based synthetic surfactant (lucinactant) in a model of Meconium Aspiration Syndrome (MAS). Eighteen newborn lambs received meconium and were randomized to: the experimental meconium installation (eMAS) group—lambs with eMAS kept on conventional mechanical ventilation (control); the SF‐Bolus group—eMAS receiving a lucinactant bolus (30 mg/ml); or the D‐SF‐Lavage group—eMAS treated with dilute lucinactant bronchoalveolar lavage (10 mg/ml). Systemic and pulmonary arterial pressures, blood gases, and pulmonary mechanics were recorded for 180 min. In addition, the intrapulmonary distribution of the lucinactant was determined using dye‐labeled microspheres. Following meconium instillation, severe hypoxia, hypercapnia, acidosis, and pulmonary hypertension developed, and dynamic compliance decreased (50% from baseline). After lung lavage with dilute lucinactant, gas exchange significantly improved versus bolus instillation (P < 0.05). Further, only in the lavage group did pulmonary arterial pressure return to basal values and dynamic compliance significantly increased. Both lung lavage and bolus techniques for the administration of lucinactant resulted in a non‐uniform lung distribution. In conclusion, in newborn lambs with respiratory failure and pulmonary hypertension induced by meconium, lung lavage with dilute lucinactant seems to be an effective and safe alternative for treatment for MAS. Pediatr. Pulmonol. 2011; 46:991–999. © 2011 Wiley‐Liss, Inc.     

应用体外膜肺氧合技术治疗胎粪吸入综合征一例及文献复习

目的探讨应用体外膜肺氧合技术（extracorporeal membrane oxygenation,ECMO）救治重症新生儿胎粪吸入综合征的治疗方法。方法报告1例应用ECMO救治重症新生儿胎粪吸入综合征的过程,并进行文献复习。结果患儿病情危重,经使用肺表面活性物质、高频振荡辅助通气及一氧化氮吸入等治疗后效果欠佳,后予ECMO治疗有效。最终治愈出院。结论对于危重症胎粪吸入综合征患儿可适当放宽ECMO治疗指征,及早予ECMO治疗。但需注意术中及术后感染、神经系统损害等相关并发症。     

一氧化氮及一氧化氮合酶在低氧性肺动脉高压中的研究进展

一氧化氮可调节肺血管张力,维持肺血管正常结构和肺循环的低阻力状态,在低氧性肺动脉高压的发生机制中起重要作用.由于一氧化氮具有独特的理化性质和生物学活性,因此目前研究主要集中在对其合成的关键酶一氧化氮合酶.下面就一氧化氮、一氧化氮合酶在低氧性肺动脉高压发病中的作用机制及临床应用的研究作一简单综述.     

内皮型一氧化氮合酶基因多态性与慢性阻塞性肺疾病肺动脉高压的相关性研究

慢性阻塞性肺疾病（COPD）的发生受遗传及环境因素的共同影响。不同种族及民族其临床表现、严重程度的差异,以及家族聚集性提示疾病可能存在遗传易感性。近年来人们主要研究了3个内皮型一氧化氮合酶（eNOS）基因多态性位点与COPD肺动脉高压的关系：位于第4内含子上27bp数目可变的串联重复序列（VNRT）;位于第7外显子,由894碱基G突变成T（G894T）,导致相应蛋白产物第298位的谷氨酸（Glu）被替换成天冬氨酸（Asp）;CA重复序列,现已有研究表明,eNOS基因多态性可能影响内皮NO释放水平,eNOS基因是COPD肺动脉高压的易感基因。     

Type I nitric oxide synthase is decreased in the fetal pulmonary circulation of hypertensive lambs

The nitric oxide (NO)/guanosine 3',5'-cyclic monophosphate (cGMP) pathway plays an essential role in mediating pulmonary vasodilatation during transition of the pulmonary circulation at birth. We used immunoblot analysis (Western) and semiquantitative immunohistochemistry to study the presence, distribution, and relative amounts of type I nitric oxide synthase (NOS-I). Immunoblots were performed on normal fetal sheep lungs, whereas immunohistochemistry for NOS-I was compared between lungs from normal fetal lambs vs. fetal lambs with persistent pulmonary hypertension of the newborn (PPHN) induced by ligation of the ductus arteriosus.Western blot analysis using a polyclonal antibody detected NOS-I protein in homogenates of normal fetal sheep lungs. Abundant NOS-I immunoreactivity was observed exclusively in the precapillary resistance vessels, i.e., terminal bronchiole-associated arteries (TA) and respiratory bronchiole-associated arteries (RA) in normal fetal lung. In marked contrast, immunoreactivity for NOS-I was significantly reduced in the TA and RA of hypertensive lungs.We conclude that there is a heterogeneous distribution of NOS-I in the normal fetal sheep lung, but that NOS-I staining is significantly reduced in lambs with PPHN.     

Measurement of lung volumes and pulmonary mechanics during weaning of newborn infants with intractable respiratory failure from extracorporeal membrane oxygenation

Newborn infants with intractable respiratory failure who require extracorporeal membrane oxygenation (ECMO) experience diffuse pulmonary atelectasis shortly after initiation of ECMO. Atelectasis is likely due to the primary lung injury and the reduction of applied inspiratory ventilator pressure when the respirator settings are changed to the “rest settings.” These pathophysiologic changes result in a decrease in lung compliance and lung volumes. We hypothesized that improving lung functions observed during ECMO and indicated by an increase in lung volumes will predict successful weaning from ECMO. Sixteen infants (mean SEM: gestational age, 40.3 ± 0.3 weeks; birth weight, 3.5 ± 0.1 kg) with meconium aspiration syndrome (n = 13), sepsis (n = 2), and persistent pulmonary hypertension (n = 1) were studied. We measured passive respiratory system mechanics and lung volumes initially during full ECMO support (115 ± 18 h on ECMO, Study I), and then within 24 h prior to weaning from ECMO (Study 11). Respiratory system compliance (C_rs), respiratory system resistance (Rrs), functional residual capacity (FRC), and tidal volume (V_T) were measured. Prior to Study I lung volumes were too small to be detected. C, increased between Study I and Study II (0.41±0.05 to 0.63±0.05 mL/cmH₂O/kg, P < 0.05), and V_T, increased between Study I and Study II (5.6 ± 0.6 to 10.4 ± 0.8mL/kg, P = 0.0005). FRC increased from 3.6 ± 1.0 to 7.9 ± 0.9mL/kg(P = 0.0001). There was no change in R_rs (88±8 to 89 ± 6 cm H₂O/Us, P = 0.9). The combination of C_rs > 0.5 mL/cmH₂O/kg and FRC > 5 mL/kg was a better predictor (P = 0.0002) of readiness to wean from ECMO than either C (>0.5 mL/cmH₂O/kg, P = 0.057) or FRC (>5 mL/kg, P = 0.007) alone. The combination of FRC and C_rs had a sensitivity of 73.3% and specificity of 100% for successful decannulation. We conclude that repeated measurements of FRC and C_rs can assess lung recovery and may assist in establishing criteria for successful weaning from ECMO. Pediatr Pulmonol. 1995; 20:145–151 . © 1995 Wiley-Liss, Inc.     

A safe clinical system for nitric oxide inhalation therapy for pediatric patients

A safe clinical system for nitric oxide (NO) inhalation therapy was developed. The system consists of three parts: a NO controller, a NO monitor, and a patient circuit. NO gas flow and carrier gas flow are controlled by a special rust-proof thermal mass flowmeter. Standard gas quality NO gas (10,000 ppm, balance nitrogen) is used. The outlet of the NO gas tank is connected to the distal end of a heated humidifer that is very close (12 mL) to the patient, to decrease acidic water precipitation and decrease contact time between NO and oxygen (O₂). Fail-safe mechanisms to prevent the delivery of a hypoxic mixture or excessive NO concentration are incorporated. Inspiratory NO concentration is continuously monitored by a modified electrochemical NO meter. The patient circuit consists of a breathing circuit and a ventilator with a scavenging unit. A modified Mapleson D type circuit is used. Fresh gas, humidified and mixed with NO, is introduced to the patient connection port. A mechanical ventilator, either of conventional or of high-frequency oscillation type, is connected to the expiratory limb of the Mapleson D circuit. A coaxial scavenging unit including activated charcoal is placed in between the expiratory limb and the ventilator. The adjustment of inspiratory NO concentration (y) was accurate over a wide range (1–80 ppm) of concentrations (x) (y = 0.36 + 0.96x, R² = 0.999, n = 45) and showed good agreement with the chemiluminescence method. Inspiratory nitrous oxide (NO₂) concentration was less than 0.3 ppm, and acidic water accumulation as measured by NO⁻₂ and NO⁻₃ was less than 5 ppm, even at an extremely high NO concentration of 80 ppm with an F₁O₂ of 1.0 and 10 L/min of fresh gas flow. Environmental NO and NO₂ concentrations in the ICU remained below 0.005 and 0.05 ppm, respectively. This system was used clinically on 214 pediatric patients and proved to be accurate, safe, and useful. Pediatr Pulmonol. 1996; 22:174–181. © 1996 Wiley-Liss, Inc.     

Inhaled ultrasonically nebulized distilled water decreases exhaled nitric oxide in asthma

Abstract Exhaled nitric oxide (eNO) is increasingly used as a marker of disease activity in asthma. Inhaled hypertonic saline has been shown to induce bronchoconstriction and to decrease eNO in asthmatic subjects, whereas the effects of hypotonic solutions on eNO in these patients have not been studied. To evaluate the effect of ultrasonically nebulized distilled water (UNDW), an indirect hypotonic stimulus, on eNO, 17 asthmatic patients were enrolled and eNO from lower airways was measured by chemiluminescence. UNDW significantly reduced FEV₁ ≥ 20% in 9 subjects (UNDW+), but had no effect in eight patients (UNDW−). Baseline eNO concentration were found to be 51.3 ± 11.1 ppb in UNDW+ and 32.9 ± 7.5 ppb in UNDW− patients, respectively (p = 0.199, NS). UNDW inhalation significantly decreased eNO (from 51.3 ± 11.1 ppb to 31.0 ± 7.1 ppb in UNDW+ (p < 0.020, n = 9) and from 32.9 ± 7.5 ppb to 26.2 ± 7.3 ppb in UNDW− subjects (p < 0.024, n = 8), respectively). eNO percentage reduction in UNDW+ patients was significantly higher compared with UNDW− subjects (−37 ± 4% vs −23 ± 3%, p = 0.021). There was no correlation between FEV₁ changes and eNO percentage decreases in both UNDW+ and UNDW− subjects. In UNDW+ patients, acute bronchodilation induced by salbutamol caused a recovery in both FEV₁ and eNO, though eNO levels remained lower than baseline values. We concluded that UNDW inhalation can significantly decrease eNO in asthmatic patients, either responders or nonresponders to this indirect osmotic challenge; the reduction in eNO levels was only partly dependent on acute changes in airway caliber.     

Magnesium causes nitric oxide independent coronary artery vasodilation in humans

OBJECTIVE—To determine how magnesium affects human coronary arteries and whether endothelium derived nitric oxide (EDNO) is involved in the coronary arterial response to magnesium.
DESIGN—Quantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthase inhibitor N^G-monomethyl-L-arginine (L-NMMA) on magnesium induced dilation of the epicardial and resistance coronary arteries.
SETTING—Hiroshima University Hospital a tertiary cardiology centre.
PATIENTS—17 patients with angiographically normal coronary arteries.
INTERVENTIONS—Magnesium sulfate (MgSO₄) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the left coronary ostium before and after intracoronary infusion of L-NMMA.
MAIN OUTCOME MEASURES—Diameter of the proximal and distal segments of the epicardial coronary arteries and coronary blood flow.
RESULTS—At a dose of 0.02 mmol/min, MgSO₄ did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO₄ caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11 (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood flow (79.3 (7.5) to 101.4 (9.9) ml/min, p < 0.001 v baseline for all). MgSO₄ increased the changes in these parameters after the infusion of L-NMMA (p < 0.001 v baseline).
CONCLUSIONS—Magnesium dilates both the epicardial and resistance coronary arteries in humans. Furthermore, the coronary arterial response to magnesium is dose dependent and independent of EDNO.


Keywords: coronary artery; coronary blood flow; magnesium sulfate; nitric oxide     

Inhaled nitric oxide,oxygen, and alkalosis: Dose‐response interactions in a lamb model of pulmonary hypertension

Inhaled nitric oxide (NO) is currently used as an adjuvant therapy for a variety of pulmonary hypertensive disorders. In both animal and human studies, inhaled NO induces selective, dose‐dependent pulmonary vasodilation. However, its potential interactions with other simultaneously used pulmonary vasodilator therapies have not been studied. Therefore, the objective of this study was to determine the potential dose‐response interactions of inhaled NO, oxygen, and alkalosis therapies. Fourteen newborn lambs (age 1–6 days) were instrumented to measure vascular pressures and left pulmonary artery blood flow. After recovery, the lambs were sedated and mechanically ventilated. During steady‐state pulmonary hypertension induced by U46619 (a thromboxane A₂ mimic), the lambs were exposed to the following conditions: Protocol A, inhaled NO (0, 5, 40, and 80 ppm) and inspired oxygen concentrations (FiO₂) of 0.21, 0.50, and 1.00; and Protocol B, inhaled NO (0, 5, 40, and 80 ppm) and arterial pH levels of 7.30, 7.40, 7.50, and 7.60. Each condition (in randomly chosen order) was maintained for 10 min, and all variables were allowed to return to baseline between conditions. Inhaled NO, oxygen, and alkalosis produced dose‐dependent decreases in mean pulmonary arterial pressures (P < 0.05). Systemic arterial pressure remained unchanged. At 5 ppm of inhaled NO, alkalosis and oxygen induced further dose‐dependent decreases in mean pulmonary arterial pressures (P<0.05). At inhaled NO doses >5 ppm, alkalosis induced further dose‐independent decreases in mean pulmonary arterial pressure, while oxygen did not. We conclude that in this animal model, oxygen, alkalosis, and inhaled NO induced selective, dose‐dependent pulmonary vasodilation. However, when combined, a systemic arterial pH >7.40 augmented inhaled NO‐induced pulmonary vasodilation, while an FiO₂ >0.5 did not. Therefore, weaning high FiO₂ during inhaled NO therapy should be considered, since it may not diminish the pulmonary vasodilating effects. Further studies are warranted to guide the clinical weaning strategies of these pulmonary vasodilator therapies. Pediatr Pulmonol. 1999; 28:3–11. © 1999 Wiley‐Liss, Inc.     

Changes in arterial oxygen tension when weaning neonates from inhaled nitric oxide.

We set out to evaluate changes in arterial oxygen tension (PaO(2)) when weaning neonates from inhaled nitric oxide (INO). We reviewed the records of 505 prospectively collected INO weaning attempts on 84 neonates with hypoxic respiratory failure. PaO(2) values before and 30 min after weaning attempts were recorded. Relationships between change in PaO(2) and decreases in INO concentrations were investigated using regression analysis and ANOVA. PaO(2) decreased (-18.7 +/- 1.8 torr; P < 0.001); when weaning INO. A stepwise decline in PaO(2) was observed weaning INO from 40 ppm. The greatest decline occurred when INO was discontinued (-42.1 +/- 4.1 torr). Forward stepwise multiple regression using variables with significant relationships to the decline in PaO(2) identified the specific dose reduction 7(P < 0.001), the prewean PaO(2) (P < 0.001), and surfactant therapy (P = 0.018) as the variables best describing the change in PaO(2)(P = 0.004, r = 0.51). In conclusion, a graded decline in PaO(2) occurs when reducing INO. INO should be weaned to less than 1 ppm before discontinuing its use. Prior surfactant treatment appears to enhance the oxygenation reserve when weaning INO.     

硫化氢供体对实验性门静脉高压及内源性一氧化氮/一氧化氮合酶体系的影响

目的探讨硫化氢供体一硫氢化钠（sodium hydrosulfide，NaHS）对大鼠门静脉高压及内源性一氧化氮（nitric monoxide，NO）／一氧化氮合酶（nitricoxide synthase，NOS）体系的影响。方法将30只健康成年雄性sD大鼠随机分为4组：部分门静脉结扎（partly portal vein ligation，PPVL）组（10只）、PPVL＋NariS组（10只）、假手术组（5只）和正常组（5只）。PPVL组和PPVL＋NaHS组行部分门静脉结扎术建立门静脉高压的动物模型。模型制作14天后，分别测定各组大鼠的门静脉压力（PVP）和平均动脉压力（MAP）；采用免疫组织化学检测大鼠肝细胞中一氧化氮合酶（NOS2、NOSS）的蛋白水平表达情况，RT-PCR方法检测大鼠肝组织中NOS2和NOS3的mRNA水平的表达情况。结果术后14d，假手术组和正常组比较，各项检测指标无显著差异，NOS2蛋白及mR-NA水平未见明显表达；NOS3蛋白及mRNA表达水平无显著差异。PPVL组与假手术组比较，PVP明显升高（P〈0．05），MAP则下降（P〈0．05），PPVL＋NaHS组与PPVL组相比较，PVP进一步升高（P〈0．05），MAP则进一步降低（P〈0．05）。PPVL组和PPVL＋NaHS组NOS2在蛋白及mRNA水平均有表达，且后者NOS2蛋白及mRNA表达水平减少（P〈0．05）。4组之间NOS3的蛋白及mRNA表达水平则无显著差异。结论H2S参与了门静脉高压的形成与发展，NaHS可以加重门静脉高压，其作用可能与NO／NOS2体系有关。．     

一氧化氮和前列腺素在门静脉高压性胃病大鼠胃粘膜灌注中的作用

目的 探讨一氧化氮（NO）和前列腺素在门静脉高压性胃病（PHG）大鼠胃粘膜灌注中的作用。方法 部分结扎大鼠门静脉主干2周后,采用中性红清除率法测定大鼠胃粘膜血流量（GMBF）,同时观察门静脉压力（PVP）的变化。结果 PHG组大鼠GMBF和PVP显著高于假手术组（t=3.431、3．312,P＜0．01）。低剂量的NO合成酶抑制剂L－硝基－精氨酸甲酯（L－NAME）呈剂量依赖性降低PHG大鼠GMBF,而对假手术组GMBF无明显影响;高剂量的L－NAME（12mg/kg)能非常显著降低PHG和假手术组大鼠GMBF。前列腺素环氧合酶抑制剂消炎痛能明显降低PHG组大鼠GMBF,而对假手术组GMBF无明显影响;预先给消炎痛处理后在假手术组大鼠中,静脉注射低剂量L－NAME（4mg/kg)前后GMBF无明显变化,高剂量L－NAME（12mg/kg)降低大鼠的GMBF与未用消炎痛处理组比无明显变化;预先给消炎痛处理后在PHG组大鼠中,L－NAME剂量（4mg/kg、12mg/kg)依赖性降低大鼠的GMBF与未用消炎痛处理组比无明显改变。结论 NO、前列腺素在调节PHG大鼠的GMBF起重要作用,但两者无协同作用。