Acute inhalation toxicity of soman and sarin in baboons.
Adult baboons (Papio sp.; 8-12 kg) were anesthesized with sodium pentobarbital (20 mg/kg iv). The animals were instrumented for measurement of mean blood pressure (MBP), pulmonary artery pressure (PAP), ECG, arterial and mixed venous blood gases, lung volumes, lung pressures, and efferent phrenic nerve activity. Bronchoalveolar lavage (BAL) was performed. Studies were done prior to exposure, at intervals during the first 4 hr postexposure, and at 4 and 28 days after exposure. Control animals received a sham exposure to 2-propanol (N = 5). Soman (pinacolyl methylphosphonofluoridate) at 13.14 micrograms/kg (2 X LD50) was vaporized into the upper airway in a second group of animals (N = 5), and sarin (isopropyl methylphosphonofluoride) 30 micrograms/kg (2 X LD50) was vaporized into a third group of animals (N = 4). Controls showed no change in any parameter either immediately after diluent exposure or during the monitoring period. Soman and sarin produced a decline in MBP and bradyarrhythmias that were reversed with atropine. Apnea occurred in all soman- and sarin-exposed animals within 5 min postexposure, and was associated with absence of phrenic nerve signal. Ventilation was mechanically supported until the animal could maintain normal arterial blood gases during spontaneous breathing. BAL studies revealed an increase in total white cell population and neutrophils at 4 hr in all three groups. There were signs of impaired hemodynamics and persistent lung injury for 4 days that resolved by 28 days after exposure. In conclusion, inhalation of soman and sarin in the baboon is associated with cardiac arrhythmias, development of apnea, and a significant decrease in MBP. Inhalation exposure also resulted in a persistent influx of neutrophils and hypoxemia.
Anzueto
A
A
Department of Medicine, University of Texas Health Science Center, San Antonio.
deLemos
R A
RA
Seidenfeld
J
J
Moore
G
G
Hamil
H
H
Johnson
D
D
Jenkinson
S G
SG
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001049:Apnea / Q000139:chemically induced; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003964:Diaphragm / Q000187:drug effects; D006327:Heart Block / Q000139:chemically induced; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000139:chemically induced; D007275:Injections, Intravenous; D008168:Lung / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010215:Papio / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D012524:Sarin / Q000008:administration & dosage / Q000633:toxicity*; D012999:Soman / Q000008:administration & dosage / Q000633:toxicity*
D009943:Organophosphorus Compounds; D001285:Atropine; D012999:Soman; D012524:Sarin