Michael J. Hosko

Experimental Human Exposure to Carbon Monoxide

Human volunteers were exposed to carbon monoxide at concentrations of < 1, 25, 50, 100, 200, 500, and 1,000 ppm for periods of one-half to 24 hours. No untoward effects were observed in sedentary males exposed to 100 ppm for eight hours. Exposures producing carboxyhemoglobin saturations greater than 15% to 20% resulted in delayed headaches, changes in the visual evoked response, and impairment of manual coordination.

Experimental Human Exposure to Methylene Chloride

Inhalation of methylene chloride vapor In concentrations of 500 to 1,000 ppm for one to two hours was followed promptly by a sustained elevation of carboxyhemoglobin level in all 11 subjects studied. The evidence suggests that carbon monoxide may fee a metabolite of methylene chloride and that exposure to concentrations of methylene chloride that do not exceed the Industrial Threshold Limit Value for that solvent may result in a carboxyhemoglobin saturation level in excess of that allowable from carbon monoxide itself. In addition, methylene chloride produced signs and symptoms of central nervous system depression in subjects exposed to vapor concentrations of 1,000 ppm.

Carboxyhemoglobin Elevation after Exposure to Dichloromethane

Inhalation of dichloromethane vapor in concentrations of 500 to 1000 parts per million for 1 to 2 hours promptly initiated the formation of significant quantities of carbon monoxide in human subjects. The evidence suggests that carbon monoxide may be a metabolite of dichloromethane and, that exposure to concentrations of dichloromethane below the industrial threshold limit values may result in the formation of carbon monoxide in amounts that exceed the allowable limits.

Experimental Human Exposure to High Concentrations of Carbon Monoxide

Six healthy male human volunteers were exposed to seven high carbon monoxide (CO) concentrations ranging from 1,000 ppm for ten minutes to 35,600 ppm for 45 seconds. Carbon monoxide was rapidly absorbed and the increase in percent carboxyhemoglobin (COHb) saturation in venous blood per liter of CO mixture inhaled could be accurately predicted by the equation, log (Δ% carboxyhemoglobsn/liter) = 1.036 log (ppm CO inhaled) -4.4793. The abrupt increase in carboxyhemoglobin concentration of 11.6% and 9.1% saturation in two subjects produced the immediate onset of mild frontal headache. The subject exposed to 35,600 ppm demonstrated slight sagging of the ST-segsnent of lead II. This occurred 20 seconds after the exposure had started and persisted for ten minutes after exposure. Neither the spontaneous nor the evoked electrical activity of the brain exhibited significant changes which could be attributed to CO exposure over the range studied.

Effect of carbon monoxide on time perception

Twenty-seven healthy, adult, male and female volunteers were exposed to carbon monoxide at concentrations of < 2, 50, 100, 200, and, 500 ppm for periods up to five hours for the purpose of determining the effect of this gas on time perception. These exposures, which resulted in a range of carboxyhemoglobin saturations up to 20%, produced no impairment in the ability of the subjects to perform the Beard-Wertheim time discrimination test, to estimate 10- or 30-second intervals, or to perform the Marquette time estimation test.

Experimental human exposure to propylene glycol dinitrate

Abstract Human volunteers were exposed in a controlled-environment chamber to propylene glycol dinitrate vapor at concentrations of 0.03, 0.1, 0.2, 0.35, 0.5, and 1.5 ppm. Physiological and central nervous system responses to the exposures were monitored. Exposure to concentrations of 0.2 ppm or greater produced disruption of the organization of the visual evoked response (VER) and headache in the majority of subjects. Subjects repeatedly exposed to 0.2 ppm for 8 hr on a daily basis developed a tolerance to the induction of headaches, but the alteration in VER morphology appeared cumulative. Marked impairment in balance became manifest after exposure to 0.5 ppm for 6.5 hr, while 40 min of exposure to 1.5 ppm added eye irritation to the list of symptoms.

The effect of carbon monoxide on the visual evoked response in man and the spontaneous electroencephalogram.

Human volunteers were exposed to carbon monoxide at concentrations ranging from 1 to 1,000 ppm for 0.50 to 24 hours. Carboxyhemoglobin (COHb) levels greater than 20% produced changes in the visual evoked response similar to those previously described in animals. The amplitude of the 2–3–4 wave complex was increased and was accompanied by a negative-going shift in the 5a-6 waves. Carboxyhemoglobin levels approaching 33% did not alter gross spontaneous electroencephalographic activity.

Technique for rapid, permanent documentation of intracerebral electrode sites.

Abstract Formalin fixed brains are blocked and frozen in 20% polyethylene glycol 6000. The blocks are oriented and 50 to 150 μ thick sections are cut to expose electrode tracts. An appropriate unstained section is mounted in glycerol-saline on a slide. The section is obliquely transilluminated from below and photographed on Polaroid film using a camera fitted with an extension bellows and macro lens. The total time required to obtain a permanent record of a selected section is less than five minutes. No darkroom facilities are required.

Hypothermic effects of intraventricular and intravenous administration of cannabinoids in intact and brainstem transected cats

Abstract Δ 9 -Tetrahydrocannabinol ( Δ 9 -THC, 500 μg in 40 μl), and the synthetic cannabinoid Dimethylheptylpuran (DMHP, 75 μg in 6.0 μl) were injected into ventricles III or IV of chronically implanted unanesthetized cats to determine the effect on body temperature. The hypothermia induced by administration of Δ 9 -THC into ventricle IV was faster in onset and reached a greater maximum than that induced by ventricle HI administration. Five hundred μg (i.v.) of Δ 9 -THC produced significantly less hypothermia than interventricular microinjection. Administration of Δ 9 -THC (2 mg/kg i.v.) to animals with a midcollicular transection produced significant decreases in blood pressure, heart rate, and body temperature when compared to animals receiving vehicle alone. Cats transected at C-1 were utilized to determine the rate at which body temperature was lost in animals unable to temperature regulate. Δ 9 -Tetrahydrocannabinol had no effect in these preparations indicating that direct peripheral mechanisms have little or no role in Δ 9 -THC induced hypothermia. It was further noted that Δ 9 -THC had little effect on blood pressure or heart rate in C-1 transected animals. These findings suggest a caudal brain stem site of action for the hypothermie effect of the cannabinoids.

Effect of Δ9-tetrahydrocannabinol on hypothalamic thermosensitive units

Abstract Thermosensitive anterior hypothalamic neurons (pre-optic region) were studied in urethane and chloralose anesthetized cats in an attempt to characterize the hypothermic action of Δ 9 -THC at the neuronal level. One hundred and seventy-eight single neurons were isolated and subjected to thermal challenge, 66 were found to reproducibly alter firing frequency at a significant level (thermosensitivity (T.S.) > 0.75). Twenty-one of these units met the criteria for primary thermodetectors, 34 were heat-sensitive interneurons, and 11 were cold-sensitive interneurons. Administration of Δ 9 -THC (1.0–2.0 mg/kg i.v.) decreased the spontaneous firing and increased the T.S. of the primary thermodetector units. Δ 9 -THC also increased the spontaneous firing frequency as well as the T.S. of heat-sensitive interneurons, while decreasing both the T.S. and spontaneous firing of cold-sensitive interneurons. The decreased spontaneous firing of primary thermodetectors could result from altered facilitory or inhibitory influences converging on these cells. The increased thermosensitivity is consistent with the hypothesis that the pre-optic region modulates cannabinoid-induced hypothermia.