Carbonic anhydrase inhibitor attenuates ischemia-reperfusion induced acute lung injury.

Ischemia-reperfusion (IR)-induced acute lung injury (ALI) is implicated in several clinical conditions including lung transplantation, cardiopulmonary bypass surgery, re-expansion of collapsed lung from pneumothorax or pleural effusion and etc. IR-induced ALI remains a challenge in the current treatment. Carbonic anhydrase has important physiological function and influences on transport of CO2. Some investigators suggest that CO2 influences lung injury. Therefore, carbonic anhydrase should have the role in ALI. This study was undertaken to define the effect of a carbonic anhydrase inhibitor, acetazolamide (AZA), in IR-induced ALI, that was conducted in a rat model of isolated-perfused lung with 30 minutes of ischemia and 90 minutes of reperfusion. The animals were divided into six groups (n = 6 per group): sham, sham + AZA 200 mg/kg body weight (BW), IR, IR + AZA 100 mg/kg BW, IR + AZA 200 mg/kg BW and IR+ AZA 400 mg/kg BW. IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, pulmonary hypertension, neutrophilic sequestration, and an increase in the expression of pro-inflammatory cytokines. Increases in carbonic anhydrase expression and perfusate pCO2 levels were noted, while decreased Na-K-ATPase expression was noted after IR. Administration of 200mg/kg BW and 400mg/kg BW AZA significantly suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1, IL-6 and IL-17) and attenuated IR-induced lung injury, represented by decreases in pulmonary hyper-permeability, pulmonary edema, pulmonary hypertension and neutrophilic sequestration. AZA attenuated IR-induced lung injury, associated with decreases in carbonic anhydrase expression and pCO2 levels, as well as restoration of Na-K-ATPase expression.

Acute respiratory distress syndrome after zinc chloride inhalation: survival after extracorporeal life support and corticosteroid treatment.

No standard protocol exists for the treatment of acute respiratory distress syndrome induced by inhalation of smoke from a smoke bomb. In this case, a 23-year-old man was exposed to smoke from a smoke grenade for approximately 10 to 15 minutes without protective breathing apparatus. Acute respiratory distress syndrome developed subsequently, complicated by bilateral pneumothorax and pneumomediastinum 48 hours after inhalation. Despite mechanical ventilation and bilateral tube thoracostomy, the patient was severely hypoxemic 4 days after hospitalization. His condition improved upon treatment with high-dose corticosteroids, an additional 500-mg dose of methylprednisolone, and the initiation of extracorporeal life support. Arterial oxygenation decreased gradually after abrupt tapering of the corticosteroid dose and discontinuation of the life support. On day 16 of hospitalization, the patient experienced progressive deterioration of arterial oxygenation despite the intensive treatment. The initial treatment regimen (ie, corticosteroids and extracorporeal life support) was resumed, and the patient's arterial oxygenation improved. The patient survived.

Hyperbaric oxygen attenuates cell growth in skin fibroblasts cultured in a high-glucose medium.

Hyperglycemia and hypoxia synergistically retard diabetic wound healing. We investigated the direct effect of hyperbaric and normobaric hyperoxia on skin fibroblasts cultured in a high-glucose medium. Detroit 551 human dermal fibroblasts cultured in Dulbecco's modified Eagle's medium containing d-glucose had reduced cell survival compared with cells grown in normal glucose medium; survival was 27.5+/-3.8% lower in 25 mM glucose and 30.6+/-3.7% lower in 50 mM glucose. Cell survival decreased because of inhibition of cell proliferation and enhanced cell death. Daily hyperbaric oxygen therapy at 2.5 atmosphere absolute for 90 minutes on 3 consecutive days reduced cell proliferation and increased cell death in normal cultured fibroblasts. Hyperbaric oxygen therapy and high-glucose medium had a synergistic effect and reduced survival by 37.6+/-4.4% (25 mM glucose) and 39.6+/-5.1% (50 mM glucose). The effects of hyperbaric oxygen and high-glucose medium were associated with overproduction of reactive oxygen species. Our results suggest that direct exposure of skin fibroblasts to hyperbaric oxygen affects cell growth and superimposes the toxic effect of high glucose. This cytotoxicity may be related to the production of reactive oxygen species in the fibroblasts.

Effects of physical training on functional status in patients with prolonged mechanical ventilation.

BACKGROUND AND PURPOSE: Patients requiring prolonged mechanical ventilation (PMV) are frequently deconditioned because of respiratory failure precipitated by the underlying disease, the adverse effects of medications, and a period of prolonged immobilization. The effects of 6 weeks of physical training on the strength of respiratory and limb muscles, on ventilator-free time, and on functional status in patients requiring PMV were examined. SUBJECTS: Thirty-nine patients with PMV were initially enrolled in the study and were assigned to either a treatment group (n=20) or a control group (n=19). Three subjects in the treatment group and 4 subjects in the control group died during the 6-week intervention period and thus their data were excluded from the final analysis. METHODS: Subjects in the treatment group received physical training 5 days a week for 6 weeks. Strength of respiratory and limb muscles, ventilator-free time, and functional status, which was measured by the Barthel Index of Activities of Daily Living (BI) and Functional Independence Measure (FIM), were examined at baseline and at the third and sixth weeks of the study period. RESULTS: Respiratory and limb muscle strength improved significantly at the third and sixth weeks in the treatment group compared with baseline measurements. Total BI and FIM scores increased significantly in the treatment group and remained unchanged in the control group. Effect sizes of the BI and FIM scores were 2.02 and 1.93, respectively, at the sixth week. DISCUSSION AND CONCLUSION: The results show that a 6-week physical training program may improve limb muscle strength and ventilator-free time and thus improve functional outcomes in patients requiring PMV.

Effect of hyperbaric oxygen on endotoxin-induced lung injury in rats.

Oxygen therapy remains the main component of the ventilation strategy for treatment of patients with acute lung injury. Hyperbaric oxygen therapy (HBO(2)) is the intermittent administration of 100% oxygen at pressure greater than sea level and has been applied widely to alleviate a variety of hypoxia-related tissue injuries. The purpose of this study was to evaluate the effect of hyperbaric oxygen on acute lung injury induced by intratracheal spraying of lipopolysaccharide (LPS) in rats. Male Sprague-Dawley rats underwent implantation of a carotid artery catheter under general anesthesia. Aerosolized LPS was delivered twice into the lungs via intratracheal puncture. Animals were either breathing room air (n = 27) or subjected to hyperbaric oxygen (HBO(2)) exposure (n = 27) 1 h after LPS spraying. Acute lung injury was evaluated 5 h and 24 h later. Compared with the control group, intratracheal spraying of LPS caused profound hypoxemia, greater wet/dry weight ratio (W/D) of the lung (5.67 +/- 0.22 vs. 4.98 +/- 0.19), and higher protein concentration (1706 +/- 168 vs. 200 +/- 90 mg/L) and LDH activity (129 +/- 30 vs. 46 +/- 15, mAbs/min) in bronchoalveolar lavage (BAL) fluid. Intratracheal spraying of LPS also caused significant WBC sequestration in the lung tissue. HBO2 treatment significantly reverted hypoxemia, reduced lung injury measures evaluated at 5 and 24 h, and enhanced 24-h animal survival rate (chi = 5.08, P = 0.024). The malondialdehyde (MDA) concentrations in lung tissue and serum were both increased after LPS spraying. Neither single HBO(2) therapy nor five sequential daily treatments enhanced MDA production in lung tissue or serum. Our results suggested that hyperbaric oxygen might reduce acute lung injury caused by intratracheal spraying of LPS in rats. This treatment modality is not associated with enhancement of oxidative stress to the lung.