Ventilator Y-piece pressure compared with intratracheal airway pressure in healthy intubated children.

OBJECTIVE: Compare airway pressure measurements at the ventilator Y-piece of the breathing circuit (P( Y )) to intratracheal pressure measured at the distal end (P( T )) of the endotracheal tube (ETT) during mechanical ventilation and spontaneous breathing of intubated children. METHODS: Thirty children (age range 29 days to 5 years) receiving general anesthesia were intubated with an ETT incorporating a lumen embedded in its sidewall that opened at the distal end to measure P( T ). Peak inflation pressure (PIP) was measured at P( Y ) and P( T ) during positive pressure ventilation. Just before extubation, all measurements were repeated and imposed resistive work of breathing (WOBi) was calculated at both sites while breathing spontaneously. RESULTS: Average PIP was approximately 25% greater at P( Y ) (19.7 +/- 3.4 cm H(2)O) vs. P( T ) (15.0 +/- 2.9 cm H(2)O), p < 0.01. During spontaneous inhalation P( T ) was 59% lower ({bond}8.5 +/- 4.0 cm H(2)O) vs. P( Y ) ({bond}3.5 +/- 2.0 cm H(2)O), p < 0.01. WOBi measured at P( Y ) (0.10 +/- 0.02 Joule/L) was 86% less than WOBi measured at P( T ) (0.70 +/- 0.40 Joule/L), p < 0.01. CONCLUSIONS: In healthy children P( Y ) significantly overestimates PIP in the trachea during positive pressure ventilation and underestimates the intratracheal airway pressure during spontaneous inhalation. During positive pressure ventilation P( T ) better assesses the pressure generated in the airways and lungs compared to P( Y ) because P( T ) also includes the difference in airway pressure across the ETT tube due to resistance. During spontaneous inhalation, P( T ) reflects the series resistance of the ETT and ventilator circuit, while P( Y ) reflects only the resistance of the ventilator circuit, accounting for the smaller decreases in pressure. Additionally, P( Y ) underestimates the total WOBi load on the respiratory muscles. Thus, P( T ) is a more accurate reflection of pulmonary airway pressures than P( Y ) and suggests that it should be incorporated into ventilator systems to more accurately trigger the ventilator and to reduce work of breathing.

Intravascular infusion of acid promotes intrapulmonary inducible nitric oxide synthase activity and impairs blood oxygenation in rats.

OBJECTIVE: To test the hypothesis that intravascular acid infusion promotes intrapulmonary nitric oxide formation by promoting inducible nitric oxide synthase (iNOS) and inhibiting endothelial nitric oxide synthase (eNOS) expression in rats. DESIGN: Prospective, placebo controlled, randomized laboratory study. SETTING: University laboratory. SUBJECTS: Twelve male Sprague-Dawley rats weighing 317 +/- 30 g served as study subjects. All animals were anesthetized, paralyzed, and mechanically ventilated throughout the experiment. INTERVENTIONS: The animals were randomized to receive either 0.1 N hydrochloric acid or 0.9% saline intravenously. The infusions were initially given at a rate of 11 mL/kg/hr for 15 mins and then at a rate of 0.95 mL/kg/hr for the remainder of the experiment. Exhaled nitric oxide concentrations and hemodynamic measurements were monitored throughout the experiment. Lung tissues were harvested for Western blot analysis and immunostaining 4 hrs after starting the intravascular infusion. MEASUREMENT AND MAIN RESULTS: At the end of the experiment, we found more than a four-fold higher concentration of exhaled nitric oxide in the acid-treated animals than in the saline-treated animals (p <.001). Western blot analysis revealed that the acid infusion increased intrapulmonary iNOS concentrations (p <.001), yet it decreased intrapulmonary eNOS concentrations (p =.009). Acid-related lung injury manifested as a decrease in blood oxygen tensions (p =.045) and as an increase in lung homogenate interleukin-6 concentrations (p =.003). CONCLUSIONS: Our results reveal that hydrochloric acid infusion stimulates intrapulmonary nitric oxide formation at least in part by promoting the expression of iNOS. Our findings suggest that correcting acidosis should attenuate iNOS formation. Our data also support the idea that metabolic acidosis itself can lead to impaired intrapulmonary gas exchange and increased expression of pro-inflammatory cytokines such as interleukin-6. Whether the induction of intrapulmonary nitric oxide formation mediates or simply indicates lung injury warrants further investigation.

Dexamethasone suppresses iNOS yet induces GTPCH and CAT-2 mRNA expression in rat lungs.

The in vivo mechanisms by which glucocorticoids inhibit nitric oxide expression await detailed investigation. In cell culture experiments, glucocorticoids have been shown to inhibit inducible nitric oxide synthase (iNOS) formation and activity. Glucocorticoids can inhibit iNOS activity in cultured cells by blocking arginine transport and inhibiting tetrahydrobiopterin biosynthesis. We recently reported that changes in intrapulmonary formation of nitric oxide in endotoxemic rats correspond with changes in transcription of the predominant arginine transporter cationic amino acid transporter (CAT)-2. Realizing that hemorrhagic shock induces nitric oxide overproduction in intact animals, we sought to explore whether glucocorticoids attenuate hemorrhagic shock-induced increases in intrapulmonary nitric oxide formation and whether they might do so by inhibiting the formation of tetrahydrobiopterin, iNOS protein, and CAT-2. We randomly assigned 10 male Sprague-Dawley rats to receive dexamethasone or normal saline. Bleeding the animals to a mean systemic blood pressure of between 40 and 45 mmHg created the hemorrhagic shock. Dexamethasone abrogated the increase in exhaled nitric oxide concentrations caused by hemorrhagic shock. At the end of the experiment, plasma nitrate/nitrite values were lower in the dexamethasone group than in the control group. The iNOS protein concentrations were also lower in the dexamethasone group than in the control group. Dexamethasone decreased the intrapulmonary iNOS mRNA concentrations yet increased both guanosine triphosphate cyclohydrolase I mRNA and CAT-2 mRNA. Our results support the idea that dexamethasone inhibits nitric oxide formation in a manner that is independent of tetrahydrobiopterin and arginine transport yet dependent on downregulation of iNOS mRNA expression.

Resuscitation of hemorrhagic shock attenuates intrapulmonary nitric oxide formation.

Hemorrhagic shock has been shown to upregulate intrapulmonary inducible nitric oxide (NO) synthase (iNOS) expression. Increased intrapulmonary iNOS expression is reflected by increases in concentrations of NO in the airways. The purpose of this study was to examine the effects of resuscitation on this induction of intrapulmonary NO formation caused by hemorrhage. Eighteen rats were randomized to one of three groups. One group of rats was simply sham-instrumented and monitored. Two other groups experienced hemorrhagic shock (mean systemic blood pressure of 40-45 mmHg) for 60 min. In one of the hemorrhagic shock groups, resuscitation was performed by re-infusing the shed blood and supplementing it with normal saline. Compared with sham-instrumented rats, those exposed to hemorrhagic shock without subsequent resuscitation exhibited a 10-fold increase in exhaled NO concentrations. Additionally, concentrations of both intrapulmonary iNOS protein and mRNA increased. Resuscitation attenuated the hemorrhage-induced upregulation of exhaled NO, iNOS protein and iNOS mRNA. This data suggests that resuscitation attenuates the hemorrhagic shock-induced formation of intrapulmonary NO by downregulating iNOS transcription. We believe that exhaled NO concentrations provide a useful, non-invasive method of monitoring the intrapulmonary inflammatory sequelae of hemorrhagic shock.