Efficacy of ibuprofen and pentoxifylline in the treatment of phosgene-induced acute lung injury.

Phosgene, a highly reactive former warfare gas, is a deep lung irritant which produces adult respiratory distress syndrome (ARDS)-like symptoms following inhalation. Death caused by phosgene involves a latent, 6-24-h, fulminating non-cardiogenic pulmonary edema. The following dose-ranging study was designed to determine the efficacy of a non-steroidal anti-inflammatory drug, ibuprofen (IBU), and a methylxanthine, pentoxifylline (PTX). These drugs were tested singly and in combination to treat phosgene-induced acute lung injury in rats. Ibuprofen, in concentrations of 15-300 mg kg-1 (i.p.), was administered to rats 30 min before and 1 h after the start of whole-body exposure to phosgene (80 mg m-3 for 20 min). Pentoxifylline, 10-120 mg kg-1 (i.p.), was first administered 15 min prior to phosgene exposure and twice more at 45 and 105 min after the start of exposure. Five hours after phosgene inhalation, rats were euthanized, the lungs were removed and wet weight values were determined gravimetrically. Ibuprofen administered alone significantly decreased lung wet weight to body weight ratios compared with controls (P < or = 0.01) whereas PTX, at all doses tested alone, did not. In addition, the decrease in lung wet weight to body weight ratio observed with IBU+PTX could be attributed entirely to the dose of IBU employed. This is the first study to show that pre- and post-treatment with IBU can significantly reduce lung edema in rats exposed to phosgene.

Evaluation and replication of impact damage to bicycle helmets.

A group of 72 impacted bicycle helmets were collected, primarily from manufacturers with a crash replacement policy that encourages the return of damaged helmets. Each damaged helmet was thoroughly inspected and measured to determine the construction details and collision damage. Laboratory replication tests were then performed on selected samples using exemplar helmets to determine impact velocity and peak headform aceleration. The predominant impact location was the front left quarter and the replication studies indicate that the majority of impacts took place on flat surfaces from drop heights of 1 meter or less. Overall, it is evident that a large number of bicycle helmet users who have benefited from the use of a bicycle helmet, and future bicycle helmet standards must incorporate the protective requirements of this unique group.

Effects of physostigmine on the cardiopulmonary system of conscious pigs.

Physostigmine, as a pretreatment candidate for nerve agent poisoning, was examined for cardiopulmonary side effects. Cardiovascular and pulmonary parameters were monitored in unanesthetized domestic pigs which received pulmonary arterial infusion of 5 micrograms/kg/min physostigmine salicylate for 2 hr. A level of 74% inhibition of red blood cell (RBC) acetylcholinesterase (AChE) activity was attained in 45 min, and this level of carbamylation increased only slightly during the remaining infusion period. In addition to this large change in AChE activity, minor changes were observed in hematocrit, heart rate, body temperature, mean aortic pressure, pulmonary arterial wedge pressure, and pulmonary artery pressure. Typically, these parameters showed a trend toward elevated levels. Blood gases, pH, respiratory rate, tidal and minute volume, cardiac output, nonelastic resistance, and dynamic compliance were not significantly different from baseline values. The unanesthetized pig responds to physostigmine in a manner similar to that reported for other species and appears to be a suitable model for evaluating cardiopulmonary effects of cholinesterase inhibitors.

Estimation of the LCt50 of phosgene in sheep.

In all species previously studied, inhalation of toxic doses of phosgene results in varying degrees of pulmonary edema, often after a symptom-free period. The sheep is an anatomically unique animal in which to study the development of pulmonary edema by monitoring the effluent from a catheterized caudal mediastinal lymph node. In addition, the size of the sheep is sufficient to permit placement of vascular monitoring devices and withdrawal of multiple biologic samples for analyses. In spite of this, there appear to be no published reports of sheep having ever been exposed to phosgene. This study was undertaken as a dose-ranging study, in order to permit subsequent studies of phosgene inhalation toxicity in a sheep lung lymph preparation. Accordingly, the LCt50 (24 hours) was estimated to be 13,300 mg.min/m3 (3325 ppm) by "up and down" subsequent dosage selection and moving average interpolation methods.