Omer Nasiroglu

Sodium pyruvate is better than sodium chloride as a resuscitation solution in a rodent model of profound hemorrhagic shock

Pyruvate is an energy substrate that has both inotropic and antioxidant properties. In this study, we tested the hypothesis that survivorship would be better after resuscitation with 1.7% sodium pyruvate than 0.9% sodium chloride in a profound hemorrhagic shock model. The study was performed in a blinded manner. Rats were randomly assigned into two groups (ten in each group), a sodium chloride resuscitation group and a sodium pyruvate resuscitation group. After a 60-min shock period, we infused 80 ml/kg of a resuscitation solution. We continuously monitored mean arterial pressure and heart rate for 50 min after resuscitation. We recognized death by the disappearance of blood pressure pulsation and precordial movement. We performed a comparison of survivorship at 50 min post resuscitation using a Z-test of proportions. Nine (90%) of the animals that received sodium pyruvate were living 50 min after resuscitation, whereas only three (30%) of the animals that received sodium chloride survived to the same time point. We conclude that sodium pyruvate is better than sodium chloride as a resuscitation solution in a model of profound hemorrhagic shock.

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

ObjectiveTo 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. DesignProspective, placebo controlled, randomized laboratory study. SettingUniversity laboratory. SubjectsTwelve male Sprague-Dawley rats weighing 317 ± 30 g served as study subjects. All animals were anesthetized, paralyzed, and mechanically ventilated throughout the experiment. InterventionsThe 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 ResultsAt 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). ConclusionsOur 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.

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.

Ventilator Y-Piece Pressure Compared with Intratracheal Airway Pressure in Healthy Intubated Children

AbstractObjective. Compare airway pressure measurements at the ventilator Y-piece of the breathing circuit (PY) to intratracheal pressure measured at the distal end (PT) 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 PT. Peak inflation pressure (PIP) was measured at PY and PT 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 PY (19.7 ± 3.4 cm H2O) vs. PT (15.0 ± 2.9 cm H2O), p < 0.01. During spontaneous inhalation PT was 59% lower ({bond}8.5 ± 4.0 cm H2O) vs. PY ({bond}3.5 ± 2.0 cm H2O), p < 0.01. WOBi measured at PY (0.10 ± 0.02 Joule/L) was 86% less than WOBi measured at PT (0.70 ± 0.40 Joule/L), p < 0.01. Conclusions. In healthy children PY significantly overestimates PIP in the trachea during positive pressure ventilation and underestimates the intratracheal airway pressure during spontaneous inhalation. During positive pressure ventilation PT better assesses the pressure generated in the airways and lungs compared to PY because PT also includes the difference in airway pressure across the ETT tube due to resistance. During spontaneous inhalation, PT reflects the series resistance of the ETT and ventilator circuit, while PY reflects only the resistance of the ventilator circuit, accounting for the smaller decreases in pressure. Additionally, PY underestimates the total WOBi load on the respiratory muscles. Thus, PT is a more accurate reflection of pulmonary airway pressures than PY and suggests that it should be incorporated into ventilator systems to more accurately trigger the ventilator and to reduce work of breathing.

SODIUM PYRUVATE IS BETTER THAN SODIUM CHLORIDE AS A RESUSCITATION SOLUTION IN A RODENT MODEL OF PROFOUND HEMORRHAGIC SHOCK

Pyruvate is an energy substrate that has both inotropic and antioxidant properties. In this study, we tested the hypothesis that survivorship would be better after resuscitation with 1.7% sodium pyruvate than 0.9% sodium chloride in a profound hemorrhagic shock model. The study was performed in a blinded manner. Rats were randomly assigned into two groups (ten in each group), a sodium chloride resuscitation group and a sodium pyruvate resuscitation group. After a 60-min shock period, we infused 80 ml/kg of a resuscitation solution. We continuously monitored mean arterial pressure and heart rate for 50 min after resuscitation. We recognized death by the disappearance of blood pressure pulsation and precordial movement. We performed a comparison of survivorship at 50 min post resuscitation using a Z-test of proportions. Nine (90%) of the animals that received sodium pyruvate were living 50 min after resuscitation, whereas only three (30%) of the animals that received sodium chloride survived to the same time point. We conclude that sodium pyruvate is better than sodium chloride as a resuscitation solution in a model of profound hemorrhagic shock.