Pathophysiology of Soman intoxication in primates

Adult baboons were monitored during intravenous infusion of Soman (1,2,2-trimethylpropyl ester, phosphonofluoridate). Three groups of animals were studied. Two groups were anesthetized with sodium pentobarbital (initial dose, 20 mg/kg), instrumented for measurement of systemic blood pressure (BP), pulmonary artery pressure, cardiac output (CO), ECG, ventilatory flow, translaryngeal pressure (P_TL), transdiaphragmatic pressure (P_di), transpulmonary pressure (P_TP), diaphragm EMG, and efferent phrenic nerve traffic (E_ph). One group received no Soman and served as controls. In the other group, Soman was infused over 10 min at doses of 13.1, 8.21, 4.92, or 3.3 μg/kg. The onset of intoxication occurred within 7-8 min (before the end of the 10-min infusion), manifested by muscular fasciculations, stridorous breathing, copious secretions, and atrioventricular arrhythmias. Mean BP decreased to 30 mm Hg by the combination of decreased CO and decreased vascular resistance. There was a dose-related response in the onset and duration of these effects. Apnea occurred in most animals and coincided with cessation of the E_ph signal. Stimulation of the diaphragm via the phrenic nerve following apnea yielded P_di values unchanged from baseline, indicating an intact neuromuscular apparatus. All animals required ventilatory support. Some surviving animals exhibited severe behavior changes. The third group of animals was studied without anesthesia. Instrumentation was performed 3 days before using a tether system for the measurement of BP, CO, and ECG, and an arterial line for blood withdrawal. Soman was infused over 10 min at a dose of 13.1 μg/kg. The onset of intoxication occurred within 2-3 min, manifested by hyperactivity, severe muscle fasciculations which simulated grand-mal convulsions, stridorous respiratory sounds, copious secretions, and cardiac arrhythmias. Apnea and severe lactic acid acidosis developed in all animals and all required ventilatory assistance. None recovered spontaneous ventilation at the end of 4 hr.