Maria A. Mayorga

The pathology of primary blast overpressure injury

Primary blast injury occurs in civilian and military detonations and from the firing of weapon systems. The pathology of primary blast injury has been reported for the last 70 years and has primarily been limited to descriptions of gross pathology and histology. Commonly accepted tenets have not been confirmed as blast overpressure experiments in enclosures and with multiple detonations have been conducted. Organ systems other than the ear and the lung are playing a greater role in injury definition and research importance. This paper is an overview and update of the current understanding of the pathology of primary blast injury.

A model of blast overpressure injury to the lung

Despite decades of animal experiments, data on blast injury to the lung cover only a limited number of circumstances and are in a fragmented form. This paper develops a mathematical model of the chest wall dynamics and the subsequent generation of strong pressure waves within the lung, which have been hypothesized as the mediator of injury. The model has been compared to an extensive database of observed pathologies from animal tests. The incidence of injury and lethality is found to follow a log-normal correlation with the computed total energy in these waves and, when the energy is normalized by the lung volume, the lethality correlation applies to all large animal species. Small animals also correlate with the normalized energy, but at a different value, and it is speculated that structural differences, other than lung volume, may be involved. This relatively simple model allows the potential for blast injury to the lung to be determined from measured or computed pressure traces without additional animal testing. Improved occupational exposure criteria should follow from this methodology.

Low-level blast raises intracranial pressure and impairs cognitive function in rats: prophylaxis with processed cereal feed

There is increasing evidence that even low levels of blast cause brain injury, but little is known about their thresholds and mechanisms. Exposure of rats to 10-60 kPa blasts elevate intracranial pressure (ICP) in a dose-dependent manner and impair cognitive function. We have evaluated a prophylactic measure against these brain injuries in a rat animal model, consisting of feeding them processed cereal. This type of feed is known to ameliorate disturbances in secretion of body fluids and to have anti-inflammatory effects. In humans, intake of processed cereals is effective against intestinal diarrhea and also reduces the symptoms of Ménières disease. Rats were given either standard laboratory feed or processed cereal feed for 2 weeks before exposure to blast in a shock tube. The ICP was monitored at different time points up to 1 week after exposure to a 60-kPa blast, and for up to 24 h after exposure to a 30-kPa blast. Maximal ICP elevation was reached at 10 h in both groups. In the group of rats on standard feed exposed to 60 kPa, an ICP increase of 145% was noted at 10 h, and the corresponding increase in the rats fed processed cereal feed was only 50%. In rats exposed to a 30-kPa blast, those fed standard feed and processed cereal feed demonstrated increases of ICP of 80% and 40%, respectively. Cognitive function as measured by the Morris water maze was assessed in other groups of rats at 2 days after exposure to 10- or 30-kPa blasts. Their performance was significantly impaired at both exposure levels in rats on standard feed, but no functional impairment was seen in rats fed processed cereal feed.

Evaluation of impulse noise criteria using human volunteer data

Four impulse noise auditory injury criteria adopted by NATO countries, namely, the MIL-STD-1474D (USA), Pfander (Germany), Smoorenburg (Netherlands), and LAeq8 (France), are evaluated against human volunteer data. Data from subjects wearing single-hearing protection exposed to increasing blast overpressure effects were obtained from tests sponsored by the US Army Medical Research and Material Command. Using logistic regression, the four criteria were each correlated with the test data. The analysis shows that all four criteria are overly conservative by 9.6–21.2 dB for the subjects as tested. The MIL-STD-1474D for single-hearing protection is 9.6 dB lower than the observed injury threshold for 95% protection with 95% confidence for this particular group of subjects as tested. Similar conclusions can be drawn for the other three criteria.

Overview of nitrogen dioxide effects on the lung with emphasis on military relevance

Nitrogen dioxide exposure occurs in many civilian occupations as well as during military combat. Little interaction has occurred between the two communities in regards to the exchange of information about NO2 research. This presentation provides an overview of NO2 related epidemiology; available research models and issues of particular interest to both the civilian and military sectors; clinical presentations, prophylaxis and treatment; and pathophysiology and mechanisms of injury. Throughout the presentation civilian and military issues are contrasted when pertinent. The most significant difference between the civilian and military research requirements is the need for information on chronic (with and without intermittent peaks) for the former, and information on acute high-level NO2 research for the latter. Another military requirement is predicting not only injury but incapacitation. This requirement can be compared to the need of clinicians to measure impairment for patients seeking disability. Both communities are faced with the same challenges of selecting appropriate models, understanding dosimetry and its many variables, clarifying the fate of inhaled NO2, developing specific markers of injury, and elucidating the mechanisms of NO2 injury for the development of prophylactic and therapeutic agents. Further research is required in these areas and it is hoped that this symposium will be the first attempt to join civilian and military resources and expertise for future research cooperation and collaboration.

Nitrogen dioxide-induced acute lung injury in sheep

Lung mechanics, hemodynamics and blood chemistries were assessed in sheep (Ovis aries) before, and up to 24 h following, a 15-20 min exposure to either air (control) or approximately 500 ppm nitrogen dioxide (NO2). Histopathologic examinations of lung tissues were performed 24 h after exposure. Nose-only and lung-only routes of exposure were compared for effects on NO2 pathogenesis. Bronchoalveolar lavage fluids from air- and NO2-exposed sheep were analyzed for biochemical and cellular signs of NO2 insult. The influence of breathing pattern on NO2 dose was also assessed. Five hundred ppm NO2 exposure of intubated sheep (lung-only exposure) was marked by a statistically significant, albeit small, blood methemoglobin increase. The exposure induced an immediate tidal volume decrease, and an increase in both breathing rate and inspired minute ventilation. Pulmonary function, indexed by lung resistance and dynamic lung compliance, progressively deteriorated after exposure. Maximal lung resistance and dynamic lung compliance changes occurred at 24 h post exposure, concomitant with arterial hypoxemia. Bronchoalveolar lavage fluid epithelial cell number and total protein were significantly increased while macrophage number was significantly decreased within the 24 h post-exposure period. Histopathologic examination of lung tissue 24 h after NO2 revealed patchy edema, mild hemorrhage and polymorphonuclear and mononuclear leukocyte infiltration. The NO2 toxicologic profile was significantly attenuated when sheep were exposed to the gas through a face mask (nose-only exposure). Respiratory pattern was not significantly altered, lung mechanics changes were minimal, hypoxemia did not occur, and pathologic evidence of exudation was not apparent in nose-only, NO2-exposed sheep. The qualitative responses of this large animal species to high-level NO2 supports the concept of size dependent species sensitivity to NO2. In addition, when inspired minute ventilation was used as a dose-determinant, a linear relationship between NO2 dose and lung resistance was found. The importance of these findings, NO2 dose-determinants, and the utility of sheep as a large animal inhalation model are discussed.

Consequences of Brief Exposure to High Concentrations of Carbon Monoxide in Conscious Rats

Exposure to high-concentration carbon monoxide (CO) is of concern in military operations. Experimentally, the physiologic manifestations of a brief exposure to elevated levels of CO have not been fully described. This study investigated the development of acute CO poisoning in conscious male Sprague-Dawley rats (220–380 g). Animals were randomly grouped (n = 6) and exposed to either air or 1 of 6 CO concentrations (1000, 3000, 6000, 10,000, 12,000, or 24,000 ppm) in a continuous air/CO dynamic exposure chamber for 5 min. Respiration was recorded prior to and during exposures. Mixed blood carboxyhemoglobin (COHb) and pH were measured before and immediately after exposure. Before exposure the mean baselines of respiratory minute volumes (RMVs) were 312.6 ± 43.9, 275.2 ± 40.8, and 302.3 ± 39.1 ml/min for the 10,000, 12,000 and 24,000 ppm groups, respectively. In the last minute of exposure RMVs were 118.9 ± 23.7, 62.1 ± 10.4, and 22.0 ± 15.1% (p < .05) of their mean baselines in these 3 groups, respectively. Immediately after exposure, blood COHb saturations were elevated to 60.16, 63.42, and 69.37%, and blood pH levels were reduced to 7.43 ± 0.09, 7.25 ± 0.05, and 7.13 ± 0.04 in the 3 groups, respectively. Mortality during exposure was 1/12 in the 12,000 ppm group and 4/12 in the 24,000 ppm group. Deaths occurred close to the end of 5 min exposure. In each animal that died by exposure, pH was <6.87 and COHb saturation was >82%. Blood pH was unaltered and no death occurred in rats exposed to CO at concentrations <6000 ppm, although COHb saturations were elevated to 14.52, 29.94, and 57.24% in the 1000, 3000, and 6000 ppm groups, respectively. These results suggest that brief exposure to CO at concentrations <10,000 ppm may produce some significant physiological changes. However, exposure to CO at concentrations >10,000 ppm for brief periods as short as 5 min may change RMV, resulting in acute respiratory failure, acidemia, and even death.

Effects of low blast levels on the central nervous system.

Anaesthetized swine in crew positions were exposed to weapons in air or to explosives underwater. Blast parameters were correlated with those in the brain. The peak pressure in the brain (Pmax brain/air) was 0.7 for a bazooka (45 kPa), 0.5 for a howitzer (10 kPa), and 0.4 for a rifle (23 kPa). The brain/water Pmax for the detonation pulse of under water explosives was only 0.1, but 0.3–0.4 for the secondary pulses. The results indicate that low‐frequency spectra penetrate easier into the brain. Histological examination revealed small hemorrhages in rear regions of the brain. In rats, we investigated the effect of shock tube blasts. After exposure to 10 or 30 kPa, cognitive performance (Morris Water Maze) decreased by 50%. The intracranial pressure (ICP) increased in a dose dependent fashion to reach peak levels 6 h after exposure at 10 kPa and 10 h after exposure to 30 or 60 kPa. An initial ICP elevation took place 30 min after exposure to 60 kPa, and 2 and 6 h after exposure to 30 and 10 kPa, respectively. A prophylaxis, consisting of a 2 week intake of hydrothermally fermented cereals, reduced significantly the blast effect both on ICP and cognitive performance. [The authors thanks Svante Hjer, Samba Sensors AB. The study was supported by the Swedish Armed Forces and FMV.]