Effects of blast exposure on exercise performance in sheep.

BACKGROUND: The effects of blast on maximal exercise performance were investigated in sheep that were trained to perform maximal exercise. METHODS AND RESULTS: Sheep were fully instrumented for determination of pulmonary and systemic hemodynamics. Blast exposure was administered by using a compressed air driven shock tube that was positioned to primarily produce cardiopulmonary injury. Four levels of exposure were used that were known to produce sublethal injury ranging from little or no grossly observable cardiopulmonary injury (level 1) to confluent ecchymosis of the heart, lung, or both (level 4). We evaluated maximal exercise performance 1 hour after exposure to level 1, level 2, and level 3 and 24 hours after level 3 and level 4. VO2max was not significantly decreased 1 hour after exposure to level 1 but was decreased after exposure to level 2 (29.9%) and level 3 (49.3%). Significant improvement in exercise performance was observed in 24 hours, as VO2max was not significantly decreased 24 hour after level 3. VO2max was decreased 24 hour after level 4 injury (30.8%). CONCLUSION: Cardiovascular data collected during exercise suggested that acute cardiopulmonary injury is responsible for the exercise performance decrement observed 1 hour after exposure and that significant recovery of function is observed 24 hours after blast injury.

Cardiopulmonary effects of high-impulse noise exposure.

In high-energy impulse noise environments, the biomechanical coupling process between the external forces and the pathophysiology of cardiopulmonary injury is not well understood. A 12-in-diameter compressed air-driven shock tube with reflector plate was used to induce three levels of pulmonary contusion injury in a large animal model. Twenty-one anesthetized sheep were exposed to the various levels of impulse noise generated by the shock tube, with six additional sheep serving as a control group. Pathologic evaluations, performed 3 hours after exposure, showed pulmonary contusion ranging from minor petechial changes on the surface of the lung parenchyma to diffuse ecchymoses affecting as much as 60% of the lung. The gross pathologic observations of injury produced by exposure to the impulse noise produced by the shock tube were similar to those reported for blunt impact trauma or exposure to chemical or grain-dust explosions. The extent of lung injury (lung injury index) was quantitatively assessed. A semilogarithmic relationship between the lung injury index and the measured peak pressure was demonstrated. A significant linear correlation was demonstrated between lung injury index and lung weight-to-body weight ratio. Significant cardiopulmonary changes were also observed as a result of exposure to high-impulse noise. Although in most cases the degree of change was related to the severity of the injury, significant cardiopulmonary function changes were also observed in the absence of significant grossly observable pulmonary injury. Cardiac injury was indicated by decreased cardiac output and hypotension at all levels of injury and might be the result of myocardial contusion or air emboli. Pulmonary injury was demonstrated by respiratory acidosis, increases in lung resistance, and decreases in lung compliance and lung volume. Arterial PO2 appeared to be the most sensitive parameter of injury and was decreased for all measurement intervals for all exposure groups.

Maximal exercise performance-impairing effects of simulated blast overpressure in sheep.

Lung contusion has been identified as a primary blast injury. These experiments addressed a fundamental and overt endpoint of primary blast injury, incapacitation (performance decrement). Respiration, hemodynamics, and blood gases were measured in sheep undergoing incremental exercise challenge before and 1 h after simulated blast exposure of the thorax. Pathologic examination of lung tissue was performed after exposure and exercise testing. Blast overpressure was simulated in the laboratory using a compressed air-driven shock tube. Three levels of lung injury (Levels 1-3, 'Trivial', 'Slight', and 'Moderate' injury, respectively) were examined for effects on maximal oxygen consumption (VO[2max]), an index of cardiorespiratory fitness. Resting hemodynamics and blood gases were relatively normal an hour after exposure, immediately before exercise. However, Levels 1-3 lung injury were associated with average 4.8, 29.9 and 49.3% VO(2max). decreases, respectively. These performance decrements for Levels 2 and 3 were significantly different from respective controls (non-exposed). Exercise caused significant hemoconcentration in sheep under control conditions, before exposure (resting 9.5 +/- 0.9, end-exercise 11.8 +/- 0.9 g/100 ml). Blast exposure resulted in average decreases of 4.9 +/- 3.4, 12.8 +/- 4.0, and 12.6 +/- 3.3% in exercise-induced hemoconcentration for Levels 1-3 injury, respectively. Normal exercise-induced hemodynamic increases were also attenuated after exposure. Levels 2 and 3 injury resulted in average 22.6 +/- 2.9 and 18.5 +/- 11.2% stroke volume decreases, and also 22.3 +/- 8.4 and 29.0 +/- 14.2% cardiac output decreases, respectively, during exercise. While blast lung pathology and pulmonary function changes could account for post-blast performance decrements, these experiments suggest that in sheep, early after exposure, diminished hemoconcentration and cardiac disfunction may also contribute to decreased exercise performance.

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.

Tympanic membrane perforation in survivors of a SCUD missile explosion.

On February 25, 1990, an Iraqi SCUD missile exploded inside a building housing United States military personnel in Dhahran, Kingdom of Saudi Arabia. One hundred seventy-two individuals who were near the impact site at the time of the blast were interviewed and examined to determine blast injury to the ear. Tympanic membrane (TM) perforation was used as the clinical marker for aural blast injury. Thirty-four personnel had unilateral TM perforation and 28 had bilateral TM perforation. Eighty-six sustained sufficient injury to be hospitalized. Fifty-nine of hospitalized personnel (70%) had TM perforation. Of a total of 90 TM perforations, 39% were estimated to be 25% or less of the tympanic membrane surface area, 36% were 26% to 50%, 16% were 51% to 75%, and 10% were greater than 75%. Morphology of the perforations and estimated proximity to the blast were documented. Personnel distant from the blast, in open doorways or wearing headphones, had relative protection from TM perforation. Historic nuclear blast data were used to estimate the SCUD blast waveform based on measurements of the SCUD impact crater. A mathematical model based on the estimated waveform was validated against the actual field data by comparing the proximity and incidence of TM perforations in the SCUD missile explosion.

Relationship of functional residual capacity to various body measurements in normal sheep.

Functional residual capacity (FRC) was determined by nitrogen washout in 55 normal sheep. Data on various external body measurements were collected which included body weight, chest circumference, chest width, body length, height, and sternum length. In addition, data on wet lung weight and wet lung weight/body weight ratio were collected on 10 of the sheep. A significant correlation was found between FRC and all measured parameters except height and sternum length. Multiple linear regression of all external body measurements showed the best correlation of FRC to body weight and body length, while the addition of chest circumference and/or chest width did not significantly improve the correlation. Significant deviation from the population was noted in three sheep (5.5%) that had lung weight/body weight ratios which were significantly lower than the rest of the population.

Cardiopulmonary effects of a tiletamine-zolazepam combination in sheep.

To assess the effects on heart and lung function, a tiletamine-zolazepam (TZ) anesthetic combination was evaluated in 10 Dorset-type ewes. Ewes were randomly allotted to 2 equal groups. Ewes of groups 1 and 2 were given a single bolus of TZ (12 and 24 mg/kg of body weight, IV, respectively) at time zero. Hemodynamic, pulmonary, and ventilation variables were measured at 15-minute intervals to 120 minutes. Blood gas variables were evaluated at 5-minute intervals for the first 30 minutes, then at 15-minute intervals to 120 minutes. In all sheep, TZ administration induced rapid, smooth induction, with gradual and unremarkable recovery. Anesthesia duration was not significantly different between groups (mean +/- SD, 39 +/- 5 and 40 +/- 14 minutes for groups 1 and 2, respectively). Immediate drug effects included apnea, decreased mean arterial blood pressure, and arterial hypoxemia. Cardiac output was significantly decreased in both groups at all times after drug administration. Significant changes in group-1 ewes included increased pulmonary and systemic vascular resistances and decreased inspired minute ventilation, tidal volume, and respiratory airflow. Significant changes in group-2 ewes included increased systemic vascular resistance and decreased pulmonary arterial pressure, inspired minute ventilation, and respiratory airflow. Both drug dosages induced apneustic breathing patterns and caused significant changes in arterial and venous blood hemoglobin concentrations and PCV. Tiletamine-zolazepam is useful for intermediate-duration anesthesia in sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Autologous perfusion of an isolated rabbit gastrointestinal tract.

Most perfusion techniques rely on mechanical means to provide blood flow to the isolated organ for maintaining its physiological conditions. The approach usually requires a complicated mechanical system with the associated problems of blood type matching and prevention of blood cell damage. This paper describes a gastrointestinal tract perfusion technique that uses the rabbit's own cardiopulmonary system as the autologous blood supply source. The technique allows for the removal of the complete intestinal loop from the abdominal cavity of the rabbit, and maintains its blood circulation through silastic tubing connections of the catheterized portal vein and cranial and caudal mesenteric arteries. An alternative perfusion site that uses the aorta as the arterial blood supply and the vena cava as the venous return also is described. The isolated perfused GI tract may then be placed in a separate test environment for controlled experiments. For an acute animal test, the approach was found to be a convenient alternative to conventional approaches.

Three-dimensional tissue deformation in subcutaneous tissues overlying bony prominences may help to explain external load transfer to the interstitium.

Anesthetized, carefully positioned, female, weanling, white-haired pigs were used to test the hypothesis that (1) interface pressure, the pressure between the skin and an external load, can be used to predict the interstitial fluid pressure over the wings of ilia and the last dorsal spinous process and (2) three-dimensional tissue deformation of the interstitium under the load could partially explain how the external load is transferred at that site. When a 4 or 8 kg load was distributed over the hips of the pigs, the interface pressures over the ilia were approximately 145 and 207 cm H2O, respectively. Approximately 28% of this pressure was transferred to the tissue, resulting in an increase in interstitial fluid pressure of approximately 39 cm H2O for the 4 kg load and 60 cm H2O for the 8 kg load. However, over the spinous process, about 42-43% of the load was transferred to the interstitium. Subcutaneous tissue marker movement occurred along the gamma and theta spherical coordinate but no significant tissue marker movement along the phi coordinate. The latter indicates no significant twisting of the tissue while the former demonstrates three-dimensional shearing. There were also indications of tissue creep since the markers continued to move with constant loading.

Nonauditory injury threshold for repeated intense freefield impulse noise.

Exposure to impulse noise is an important occupational health concern. The risk of injury to auditory structures is well recognized and provides the cornerstone for present safety standards. For freefield impulse noise, nonauditory injury is dependent on peak pressure, positive phase duration (or impulse), and number of exposures. Trivial laryngeal petechiae are shown to precede nonauditory injury to more critical organs (ie, pulmonary and gastrointestinal systems). This study identifies the critical impulse noise thresholds causing trivial laryngeal petechial changes resulting from exposure to 5, 25, and 100 repetitions of specific levels of impulse noise. Because of anatomical differences, sheep should be slightly more susceptible to impulse noise laryngeal petechial changes than man; therefore, it seems reasonable to set the absolute limits for human occupational exposure levels below those causing laryngeal petechiae in sheep for persons wearing adequate hearing protection. This study does not address human auditory injury that may occur above or below these exposure limits even with proper hearing protection.

The cardiorespiratory effects of diazepam-ketamine and xylazine-ketamine anesthetic combinations in sheep.

The cardiorespiratory dynamics and anesthetic effects of intravenously administered diazepam-ketamine (0.375 mg kg-1/7.5 mg kg-1) and xylazine-ketamine (0.1 mg kg-1/7.5 mg kg-1) were investigated in six domestic sheep (Ovis aries). The depth of analgesia and sedation was evaluated and the effects of the anesthetic drug combinations on hemodynamics and pulmonary mechanics were monitored before, and up to 90 minutes after, drug administration. Diazepam-ketamine and xylazine-ketamine induced effective anesthesia for periods lasting 15 minutes and 25 minutes, respectively. Both drug combinations caused transient respiratory acidosis. However, no profound effects on respiration or pulmonary function were observed. Neither anesthetic regimen caused significant effects on heart rate or pulmonary hemodynamics, but they caused significant decreases in cardiac output. Xylazine-ketamine resulted in a significant decrease in mean systemic arterial blood pressure (Psa) with a concurrent decrease in systemic vascular resistance (SVR). Diazepam-ketamine caused a significant increase in SVR without affecting Psa. Xylazine-ketamine may be contraindicated in animals with compromised heart function because of its hypotensive effects. Otherwise, both drug combinations, in the doses used, can provide short-term anesthesia suitable for minor surgical procedures and painful experimental maneuvers.

Middle ear injury in animals exposed to complex blast waves inside an armored vehicle.

With greater reliance on armored vehicles of improved survivability, questions have arisen about the likelihood of the wounding of vehicle occupants from blast waves alone. In this study, we placed anesthetized animals (sheep or pigs) inside lightly armored vehicles and exposed them to the blast waves generated by one of three sizes of shaped-charge munitions. Sixty-seven animals were exposed and 15 served as controls. No difference was noted between exposed and control groups for blast injury to the respiratory or gastrointestinal tracts. In contrast, middle ear damage was observed exclusively in animals exposed to blast and was correlated strongly with the peak pressure. The ear is the organ most sensitive to blast damage, and if protectors are not used, military physicians can expect to see a high incidence of middle ear injury in modern combat. The operational consequences of such an injury are not known.

Cardiopulmonary effects of nalbuphine hydrochloride and butorphanol tartrate in sheep.

The cardiopulmonary, sedative and analgesic effects of butorphanol tartrate and nalbuphine hydrochloride were evaluated in six adult crossbred Dorset sheep (Ovis aries). The animals were divided randomly into two groups of three. The first group received butorphanol tartrate (0.5mg/Kg s.c.) followed in 3 days by nalbuphine hydrochloride (1 mg/Kg, s.c.). The second group received nalbuphine followed in 3 days by butorphanol. Cardiopulmonary parameters were evaluated at baseline (once the animal had accommodated to restraint); immediately following analgesic administration; and at 15, 30, 60, 90 and 120 minutes after analgesic administration. No significant changes (alpha greater than .05) from baseline were seen in any of the measured cardiopulmonary parameters from either the butorphanol or nalbuphine groups. Butorphanol produced the most dramatic analgesic and sedative effects with onset of both within 15 minutes of administration and peak effects occurring 30 minutes post injection. The degree of analgesia was diminished at 120 minutes while the sedative effect returned to near baseline by 90 minutes. The nalbuphine group also showed an onset of analgesia 15 minutes post injection reaching a peak effect after 30 minutes. However, onset of sedation occurred 30 minutes post injection achieving a peak effect at 60 minutes which was markedly less than that of butorphanol. As in the butorphanol group, analgesia was diminished at 120 minutes.

Computer modeling of thoracic response to blast.

Primary blast injury affects the gas-containing structures of the body. Damage to the lungs with resultant respiratory insufficiency and arterial embolization of air from alveolar pulmonary venous fistulae is the predominant cause of morbidity and mortality following high-level blast exposure. In an effort to generate a widely applicable damage-risk criterion for thoracic injury from blast we are developing a complex computer finite element model (FEM) of the thorax. Taking an engineering approach, a horizontal cross-section of the thorax is divided into small discrete units (finite elements) of homogeneous structure. The necessary physical properties (density, bulk modulus, etc.) are then determined for each element. Specifying the material constants and geometry of the elements, the computer can load the surface of the structure with some force-time function (blast pressure-time history) and calculate the resultant physical events such as displacement, compression, stress, strain, etc. Computer predictions of pressure wave phenomena in the lung parenchyma are compared with trans-bronchially measured pressures in blast-exposed animals. The model should prove useful in assessing the risk of blast injury in diverse overpressure environments and may give insight into pathophysiologic mechanisms and strategies for protection.

Long-acting intramuscular anesthetic regimen for swine.

A two-stage, long-acting, injectable anesthetic regimen which provided pain-free restraint for swine was developed using nine mixed-breed domestic pigs. Each animal was administered a first-stage drug combination consisting of meperidine hydrochloride and azaperone in the caudal thigh muscles, followed after 20 minutes by a second-stage group of injections consisting of ketamine hydrochloride combined with morphine sulfate in the same muscles of the opposite leg. A mean surgical anesthetic time of 60.6 +/- 18.6 minutes was achieved with this regime and it was found that total anesthetic time could be doubled by a second injection of the ketamine and morphine components alone. All animals had a rapid, uneventful recovery. This combination regime not only provided reliable, long-acting anesthesia but was administered easily, required no tracheal intubation and produced no significant changes in the animals' heart rate or body temperature during the anesthetic period.

Hemodynamic effects of 10% dextrose and of dextran 70 on hemorrhagic shock during exposure to hyperbaric air and hyperbaric hyperoxia.

Six groups of six conditioned dogs each were instrumented with an electromagnetic flow-meter transducer around the pulmonary artery, and indwelling silastic cannulae in the pulmonary artery, the left ventricle, the ascending aorta, and the right atrium. After allowing a minimum of 5 d for recovery, the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA), breathing 100% oxygen (PO2 2128 mm Hg) and at 6 ATA breathing air (PO2 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. This required a rather constant 40 +/- 4.5 ml X kg-1 body weight of total blood removed. Three groups, one at each depth perturbation, were then given Dextran 70, the other three groups 10% dextrose. Fluids were administered at a constant rate until the mean aortic pressure rose to within 90% of its original 1 ATA baseline value. At this point, the infusion was stopped and the total amount of fluid administered was recorded. Hemodynamic parameters were measured or calculated for eight different time periods during each experiment. The amount of Dextran 70 required did not change with hyperbaric exposure but only half as much 10% dextrose was required at depth. Dextran 70 held the cardiovascular parameters constant for 30 min following administration but after 10% dextrose, cardiac output tended to decrease at 15 and 30 min posttreatment. There were no significant differences in the cardiovascular effects of hemorrhage between or among the dogs exposed to the three different environmental conditions.

Adverse cardiovascular effects of oxytetracycline preparations and vehicles in intact awake calves.

Comparisons were made of cardiovascular effects in intact, awake, previously instrumented calves given the following oxytetracycline (OXY) preparations and components: polyvinylpyrrolidine vehicle (PVP), OXY HCl in PVP (OXY-PVP), OXY HCl (USP) in saline solution, propylene glycol, 77.8% (PG), propylene glycol vehicle (PGV), and OXY HCl in PGV (OXY-PGV). The 3 preparations containing PG caused significant increases in pulmonary arterial pressures and significant decreases in cardiac output and stroke volume. Aortic pressures were significantly decreased, as were heart rates. Both pulmonic and systemic resistances were significantly increased. There were no direct effects measured on left ventricular contractility. The aqueous OXY caused no significant changes. The PVP preparation and vehicle caused no changes in pulmonary pressures, pulmonary resistance, cardiac output, or stroke volume. Significant increases were observed in aortic pressure, heart rate, and systemic resistance. Left ventricular contractility was not changed. Seemingly, the PG-induced changes were a result of histamine release which did not appear to be dependent on prior sensitization of the calves.

Physical characteristics of pulmonary artery stenosis murmurs in calves.

To better understnad the characteristics of cardiovascular murmurs and turbulent energy transmission, we made simultaneous measurements of pressure (sound) and velocity fluctuations in the vicinity of surgically produced stenoses in the pulmonary artery of calves. We did a spectral analysis of these data and found an identifiable break frequency at which the slopes of the pressure fluctuations changed. By use of these break frequencies and the corresponding blood jet velocity and vessel diameter measurements, Strouhal numbers were calculated. The jet velocity, Reynolds number, Strouhal number, and unsteadiness parameter values changed when the vessel was stenosed. When the power spectrum curves for the velocity fluctuations and the sound were compared, they tended to show a correlation between break frequencies. We speculate that this apparent correlation indicated a transfer from turbulent to acoustic energy.

Ammonia inhalation toxicity in cats: a study of acute and chronic respiratory dysfunction.

Twenty healthy conditioned cats were pulmonary-function tested and then exposed to 1000 ppm of ammonia gas for a 10-min period. Pulmonary function tests were repeated and lung samples for pathologic evaluation were taken on days 1, 7, 21, and 35 post-exposure. Two cats were housed with the experimental cats as untreated controls. Pulmonary function data were analyzed, statistically evaluated, and compared with the pathological observations. There was good correlation between the alterations in pulmonary function observed and the pathologic lesions found. According to our findings, and those of other investigators, the pulmonary dysfunction which results from ammonia gas inhalation is biphasic in nature. The acute effects of the initial insult, which can be fatal, are almost always followed by secondary effects which can result in debilitating, chronic respiratory dysfunction. This study has characterized an animal model which could provide techniques for preventing or modifying the course of the secondary damage of ammonia gas inhalation.

The determination of the irritancy potential of surfactants using various methods of assessment.

Several animal irritancy test methods whose criteria include sensory response, pain/discomfort or tissue damage were evaluated as to their ability to assess relative irritancy potential of the following surfactants: sodium lauryl polyether (12) sulfate (SLES), Miranol C2M (MC2M), Miranol MHT (MMHT), sodium coco methyl tauride (SCMT), triethanolamine lauryl sulfate (TEALS), ammonium lauryl sulfate (ALS) and sodium lauryl sulfate (SLS). Data from the mouse upper respiratory tract and mouse writhing tests indicated that SLES, MC2M and MMHT were the least irritating and SLS, ALS and TEALS were the most irritating. The blepharospasm test did not lend itself to this type of evaluation because sequential instillation of the surfactants produced eye anesthesia. Data from the Draize eye test indicated that SLES was the least irritating while MC2M was slightly more irritating. All other surfactants were equally irritating. The Draize skin test results showed that SLES again was the least irritating at all concentrations tested and that SLS and ALS along with TEALS and SCMT were the most irritating.