Myeloperoxidase activity as a lung injury marker in the lamb model of congenital diaphragmatic hernia.

PURPOSE: The antioxidant system is the primary intracellular defense system of the lung against oxygen toxicity (neutrophil sequestration). The CDH lamb model antioxidant system is deficient. It is hypothesized that pulmonary neutrophil sequestration may play a part in the acute lung injury of CDH patients. Myeloperoxidase (MPO) is a major constituent of neutrophil cytoplasmic granules and its activity therefore is a direct measure of neutrophil presence and an indirect indicator of lung injury. METHODS: Eight lambs had left-sided diaphragmatic hernias surgically created at 80 days' gestation and were delivered by cesarean section at 140 to 145 days. Eight littermate lambs served as controls. Lambs were either killed before ventilation or were ventilated conventionally for 4 hours with 100% O(2) and then killed. The lungs were dissected en bloc and snap frozen. The samples were homogenized, sonicated, freeze-thawed, and separated by density centrifugation. Supernatants were analyzed for myeloperoxidase (MPO) activity by spectrophotometry with o-dianisidine dihydrochloride and hydrogen peroxide at 460 nm. The MPO activity was normalized to the protein content of the supernatant and expressed as units of MPO activity per milligram of protein. RESULTS: There was significantly more MPO activity in the CDH-ventilated lungs than controls similarly ventilated (3,203 +/- 665 versus 1,220 +/- 194, P =.001). There was no difference in MPO activity between the CDH and control lungs (318 +/- 57 v 348 +/- 61; P =.5). There was no difference between right and left lungs in any group. CONCLUSION: Ventilation and hyperoxia leads to neutrophil accumulation in lung tissue, which is most pronounced in the CDH lung tissue. This is a further clue to the pathophysiology of iatrogenic lung injury in CDH. The myeloperoxidase assay may now be used to evaluate antenatal or postnatal antioxidant therapies for iatrogenic lung injury in CDH.

Regional pulmonary blood flow during partial liquid ventilation in normal and acute oleic acid-induced lung-injured piglets.

OBJECTIVE: To determine the spatial distribution of pulmonary blood flow in three groups of piglets: partial liquid ventilation in normal piglets, partial liquid ventilation during acute lung injury, and conventional gas ventilation during acute lung injury. DESIGN: Prospective randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Neonatal piglets. INTERVENTIONS: Regional pulmonary blood flow was studied in 21 piglets in the supine position randomized to three different groups: a normal group that received partial liquid ventilation (Normal-PLV) and two acute lung injury groups that received an oleic acid-induced lung injury: partial liquid ventilation during acute lung injury (OA-PLV) and conventional gas ventilation during acute lung injury (OA-Control). Acute lung injury was induced by infusing oleic acid (0.15 mL/kg iv) over 30 mins. Partial liquid ventilation was instituted with perflubron (LiquiVent, 30 mL/kg) after 30 mins in the Normal-PLV and OA-PLV groups. MEASUREMENTS AND MAIN RESULTS: Arterial and venous blood gases, hemodynamics, and pulmonary mechanics were measured every 15 mins throughout the hour-long study. Pulmonary blood flow was assessed by fluorescent microsphere technique at baseline and after 30, 45, and 60 mins. In the Normal-PLV piglets, pulmonary blood flow decreased from baseline (before injury or partial liquid ventilation) in the most dependent areas of the lung (F ratio = 3.227; p < .001). In the OA-PLV piglets, pulmonary blood flow was preserved over time throughout the lung (F ratio = 1.079; p = .38). In the OA-Control piglets, pulmonary blood flow decreased in the most dependent areas of the lung and increased from baseline in less dependent slices over time (F ratio = 2.48; p = .003). CONCLUSIONS: The spatial distribution of regional pulmonary blood flow is preserved during partial liquid ventilation compared with gas ventilation in oleic acid-induced lung injury.

Extracorporeal membrane oxygenation for cardiac rescue in children with severe myocardial dysfunction.

OBJECTIVE: To assess the experience and efficacy of extracorporeal membrane oxygenation (ECMO) for cardiac rescue in patients with presumptively lethal cardiac dysfunction at the Children's Hospital of Pittsburgh. DESIGN: Retrospective analysis of patient records from a 9-yr period. SETTING: A 22-bed tertiary care pediatric intensive care unit (ICU) with an average of 1,400 admissions per year. An average of 150 open cardiotomy surgeries are performed per year, and all postoperative and severely ill cardiac patients are cared for in the ICU. PATIENTS: A total of 29 pediatric ICU patients with myocardial failure received ECMO throughout the 9-yr study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic information, underlying cardiac defect, intraoperative and postoperative data, postoperative course, details of ECMO treatment, and outcome were collected. Comparison of survivors with nonsurvivors was performed using the Mann-Whitney U test for continuous variables. Twenty-three (79%) of 29 patients recovered myocardial function while undergoing ECMO, 18 (62%) of 29 patients were successfully decannulated, and 13 (45%) of 29 patients survived to hospital discharge. Long-term survival rate was 11 (38%) of 29 patients. Three (60%) of five bridge-to-heart transplant patients survived. Eleven (65%) of 17 patients who suffered cardiac arrest before ECMO, survived to discharge and nine (53%) of these 17 patients remain long-term survivors. Survival rate in patients who required cardiac massage for > 15 mins before cannulation was six (55%) of 11 patients. CONCLUSIONS: Patients with severe myocardial dysfunction who fail conventional therapy can be successfully supported with ECMO during the period of myocardial recovery. ECMO can also provide a viable circulatory support system in patients with prolonged cardiac arrest who fail conventional resuscitation techniques. ECMO is also an effective means of support as a mechanical bridge to heart transplantation.