Walter R. Rogers

Effects of Combustion Gases on Escape Performance of the Baboon and the Rat

In postcrash aircraft fires, only a few minutes are often available for egress. To assess the potential of selected combustion gases (CO, acrolein and HCl) to impair human escape, a signalled avoidance task was developed for use with the juvenile African Savannah baboon. After a 5-minute exposure, the animal was required to select and depress the correct lever to open an escape door and then to exit into the adjacent compartment of a shuttlebox. With CO, the EC50 for escape failure was 6850 ppm. Acrolein (12 to 2780 ppm) neither prevented escape nor affected escape times, despite irritant effects at all concentrations. Similar results were obtained with HCI (190 to 17,200 ppm) in that, despite severe irritant effects, all animals successfully performed the escape task. With a comparable shuttlebox and escape paradigm for rats, the EC50 of CO was 6780 ppm. Five-minute exposures to HCI (11,800 to 76,730 ppm) did not prevent escape but severe post-exposure respiratory effects and lethality occurred at 15,000 ppm and higher. In both species, escape time was not affected by HCI but a concentration-related increase in intertrial responses was evident. The data suggest that laboratory test methods for measurement of incapacitation of rodents may be useful in evaluating potential effects of atmospheres containing CO or irritant gases on human escape capability.

Strength-duration curve for an electrically excitable tissue extended down to near 1 nanosecond

As part of a health and safety assessment of ultrawideband sources, it was useful to determine stimulation thresholds for an electrically excitable tissue down into the low nanosecond range. Stimulation thresholds were measured using gastrocnemius muscles isolated from 16 frogs (Rana sp.). Single pulses were delivered with a pair of surface electrodes, and muscle twitch was measured with an isotonic transducer. Pulse durations of 100, 10, and 1 ms; 100, 10 and 1 /spl mu/s; and 100 and /spl ap/1 ns were used. Tissue voltage and current strength-duration (S-D) curves on log-log plots had a classic appearance, with thresholds for ultrashort pulses being linear. For a pulse of /spl ap/1 ns, the mean threshold voltage in the muscle was 4.5 kV and the mean threshold peak current was 35 A. When delivered by direct contact, a single ultrawideband pulse of /spl ap/1 ns could reliably produce a biological effect, stimulation of an electrically excitable tissue. The observation that the S-D curves extended downward to /spl ap/1 ns in a linear manner suggested that classical ion channel mechanisms regulated excitation and that other processes, such as electroporation, did not occur. Although a single nanosecond pulse delivered by direct contact can elicit a biological response, such a stimulus in air is unlikely to produce an effect.

Cigarette smoking, dietary hyperlipidemia, and experimental atherosclerosis in the baboon.

In separate experiments, we fed 30 male and 25 female baboons a diet enriched in cholesterol and saturated fat for periods of 3.3 and 2.6 years. Using operant conditioning with water rewards, we trained the animals to puff on smoking machines in a human-like manner. Half of the animals smoked more than 40 cigarettes per day, while the remaining animals (controls) puffed air. Initially, the diet produced twofold (males) and threefold (females) elevations from baseline levels in serum cholesterol concentrations, but over the course of the experiments, the serum cholesterol decreased to 1.5 (males) and 2.0 (females) times baseline levels in both cigarette smokers and controls. Blood carbon monoxide concentration, plasma thiocyanate concentration, and urine cotinine concentration were significantly greater in smokers than in controls. Responses to smoking in males included lymphocytosis, elevated fasting blood glucose concentration, and decreased seminal vesicle weight. In females, hemoglobin and mean corpuscular hemoglobin concentrations were elevated. The extent of atherosclerosis was examined after 2.8 (males) and 1.6 (females) years of smoking. Among males, the extent of lesions in carotid arteries was significantly greater in smokers than in controls, but there were no significant differences in atherosclerosis in the aorta or the brachial, iliac-femoral, or coronary arteries. Among females, there were no significant differences in atherosclerosis between smokers and controls in any artery. These experiments show little effect of 2 to 3 years of cigarette smoke inhalation and concurrent modest elevation of blood carboxyhemoglobin on experimental atherosclerosis in the presence of moderate hyperlipidemia.

Cigarette smoking by baboons: In vivo assessment of particulate inhalation using bronchoal veolar lavage to recover [14C]dotriacontane☆

In order to demonstrate quantitatively that cigarette-smoking baboons inhale particulate matter into the lung, a bronchoalveolar lavage method for recovery of [14C]dotriacontane was developed. First, 9 baboons were exposed to a known dose of [14C]dotriacontane labeled particulate matter delivered in a manner providing extensive deposition of particulates in the lung. The lungs of these passively exposed animals then were lavaged so that the efficiency of recovery of the standardized lavage procedure could be determined. Second, 9 baboons actively smoked labeled cigarettes, and the lungs of these animals were lavaged to recover labeled [14C]dotriacontane. The total amount of particulate matter present in the lungs was estimated using the efficiency factor previously determined. The smoking baboons retained an average of 9% of he total cigarette particulate matter. Differences among animals in retention of particulate matter were considerable, and the inter-animal variability was related to differences in number, volume, duration, and pressure of puffs. The retention of particulate matter by baboons is similar to particulate retention by other animal smoke inhalation models.

Cigarette Smoking Baboon Model: Demonstration of Feasibility

Summary Using operant conditioning techniques and a specially designed apparatus, and without surgical manipulation or obvious stress, we trained seven baboons to puff on lighted cigarettes and to inhale cigarette smoke. Smoking behavior was maintained for up to 15 months and could be controlled by manipulating minimum puff duration, water reward, and frequency of presenting cigarettes. Concentrations of blood carbon monoxide after 3 hr of smoking equaled or exceeded those reported for heavy human cigarette smokers. The cigarette smoking baboon models human smoking performance and is a useful animal model for studying the mechanism of the effects of cigarette smoke inhalation on the cardiovascular, pulmonary, and reproductive systems.

Analysis of urinary mutagens produced by cigarette-smoking baboons.

Urine concentrates from 17 cigarette-smoking baboons and 12 sham puffers were analyzed for mutagenic activity in S. typhimurium tester strain TA1538. Both the proportion of animals exhibiting measurable mutagenic activity in urine and the mean level of mutagenic activity present were significantly greater in cigarette smoking baboons (P less than 0.05). Mutagenic activity in the urine of male and female cigarette-smoking baboons was not significantly different. Age and smoking history did not, but mean blood carboxyhemoglobin did, correlate with mutagenic activity of the urine concentrate from individual animals. Fractionation of the urine concentrates on silicic acid separated the concentrate into fractions that were more active in TA100 and others that were more active in TA1538. Further fractionation was accomplished by HPLC.

Effects of cigarette nicotine content on smoking behavior of baboons

Human cigarette smokers modify the way in which they smoke cigarettes of differing nicotine content, apparently to maintain nicotine exposure at a preferred level. The effects of changing from moderate to high or low nicotine content cigarettes were examined in 11 baboons (superspecies Papio cynocephalus) trained to smoke cigarettes for water rewards. Relative to the moderate nicotine content cigarette, the animals took significantly (p less than .05) more puffs on the high nicotine content cigarette, and the puffs on the high nicotine cigarette were significantly larger in volume. The animals made the same number of puffs, relative to the moderate nicotine content cigarette, on the low nicotine content cigarette, but the volume of the puffs was significantly smaller. The cotinine output in urine varied significantly and was directly related to cigarette nicotine content; cotinine is the primary metabolite of nicotine. Baboons, like people, prefer high nicotine content cigarettes. Nonhuman primates also regulate nicotine exposure by modification of their puffing behavior. These results indicate that the nonhuman primate also can be used as a model for the investigation of the behavioral aspects of cigarette smoking.

Thyroid hormone levels and cigarette smoking in baboons.

Abstract Using a primate animal model, two studies were undertaken to examine the effects of cigarette smoking on thyroid hormone levels. In study 1, mean total triiodothyronine (total T3) and mean total thyroxine (total T4) levels were measured in two groups of baboons (Papio cynocephalus) who were taught to smoke cigarettes using operant conditioning techniques. The smokers were divided into established and naive smokers according to pack-years of exposure. A control group of never-smoker baboons was included for comparison. Blood sampling was done after long-term cigarette consumption and again 1 week after cigarette deprivation. In the naive smoker group, mean total T3 concentrations were reduced below control group values (P < 0.05). After cigarette deprivation for 1 week, mean total T3 values returned to normal. No significant differences in total T4 levels were observed in either group. In study 2, we assessed some other indices of thyroid function. The same groups of baboons were divided into good and poor smokers by plasma cotinine and blood carboxyhemoglobin (% COHb) levels during 28 weeks of cigarette smoking activity. Immediate fluctuations and reductions in total T3 levels were observed that were not accompanied by reductions in total T4. The animals were then cigarette deprived for 1 week and blood samples were obtained every other day during this period. Significant increases in total T3 concentrations were observed in poor smokers immediately after cessation. Both groups also exhibited significant reductions (P < 0.05) in T3 uptake and free T4 index (FT4I) when compared to control group values. These data suggest that poor smokers are more susceptible to thyroid hormone level shifts than more established smokers, since the established smokers become habituated to the compounds contained in cigarette smoke through repeated exposure.

Training adaptations of baboons to light and moderate treadmill exercise

We evaluated training adaptations by 18 baboons (Papio cynocephalus anubis) to low and moderate quadrupedal walking exercise on a motorized treadmill. Moderate training produced 47% increases in lactate threshold, 63% increases in muscle citrate synthetase activity, increases in percentage of Type IIc muscle fibers, and reduced plasma insulin concentrations. Low training produced only reduced plasma insulin concentrations. Our results indicate that the baboon response to exercise training was similar to that of Homo sapiens, and dependent on exercise intensity.

Studies on the Effects of 60-Hz Electric and Magnetic Fields on Neuroendocrine Circadian Rhythmicity in Nonhuman Primates

Wilson et al. (1981, 1983, 1986) demonstrated that exposure of rats to electric fields for 3 weeks both reduces, by about 50%, the amplitude of the nocturnal peak in melatonin production by the pineal gland and delays, by about 2 hours, the time of peak melatonin production. Semm (1983), Welker et al. (1983), and Olcese and Reuss (1986) have demonstrated magnetic field effects on pineal melatonin synthesis in rodents.