Objectives: To determine the cardiovascular, autonomic, and neuromuscular effects of an IV infusion of tetrodotoxin (TTX) when ventilation is supporte'd.Methods: TTX was infused in 18 anesthetized beagles during conventional mechanical ventilation. TTX infusion continued at a rate of 9.3 p.g/kg/hr until apnea occurred with 1 minute of ventilator disconnection. Measurements included intravascular pressures, heart rate (HR), cardiac output, blood gases, displacements of the rib cage and abdomen, 0, delivery, and responses to train-of-four and tetanic peripheral nerve stimulation. Results are expressed as mean 2 SD. Results: During TTX infusion, all the dogs had discoordinate movements of the rib cage, abdomen, and limbs. Vomiting, urination, defecation, and increased salivation occurred. Nicotinic and muscarinic effects, neuromuscular blockade, and cardiovascular depression were produced by TTX. Apnea occurred in 72.0 2 17.0 minutes when a total of 119.0 ? 17.4 pg of TTX was infused. At apnea, decreases in arterial pressure, cardiac index, HR, 0, delivery, and systemic vascular resistance occurred, while pulmonary artery pressure and pulmonary vascular resistance increased. Loss of response to tetanic stimulation was closely correlated with the dose of TTX that produced apnea. Conclusion:The clinical symptoms and signs of TTX poisoning are similar to those of anticholinesterase poisons, and TTX dosing as described by this model may serve as a surrogate for organophosphorus poisoning.The model may be useful to determine optimum therapies for 'ITX poisoning and, since TTX prevents sodium influx into cells, to investigate enhanced survival in animals suffering from ischemia. Key words: tetrodotoxin; organophosphorus poisoning; simulation; overdose; toxicology; airway management. I Tetrodotoxin (TTX) is a neurotoxin found in the puffer fish. TTX produces apnea and cardiovascular depression'-' by selectively blocking axonal conduction and by preventing the increase in permeability to sodium (Na') ions associated with an action ~otential.~.' Precipitous hypotension, bradycardia, and a fall in cardiac output are reported to occur when TTX is given in bolus IV or intraperitoneal (Ip) doses sufficient to produce respiratory muscle paralysis and a~n e a .~.~. "Over a 68-year period there has been a 59% mortality rate among 6,386 people who suffered TTX poisoning after eating puffer fish liver, roe, and testes,'.* yet systematic study of TTX effects during a more clinically relevant dosing regimen remains undescribed. Gradual changes would be expected to occur following overdose with TTX after ingestion and absorption through the skin. However, respiratory failure masks the other effects of TTX.The neuromuscular blockade that results from TTX causes a similar pathologic state (by a different pharmacologic mechanism) to those of potent long-acting anticholinesterases (AChEs), which are widely used as insecticides in agriculture and used in chemical warfare.'-'' Both TTX and AChE overdoses produce vomiting, excess sal...

To assess changes in total and regional chest wall properties during nonrespiratory maneuvers, we measured electromyographic activity of various chest wall muscles, esophageal pressure, and rib cage and abdominal surface displacements in six subjects before and during various static tasks. Subjects were seated at functional residual capacity, and quasi-sinusoidal forcing at the mouth (0.4 Hz, 500 ml) was imposed during the maneuver in the absence of active breathing. Magnitude of total chest wall impedance (magnitude of Zw) increased with effort during all maneuvers; changes in phase were small. Maneuvers involving primarily muscles of the neck and rib cage--holding a 10-kg weight, 10 kg of isometric tension between the arms, and isometric neck flexion--roughly doubled the magnitude of rib cage impedance (magnitude of Zrc) and, to a lesser degree, increased magnitude of diaphragm-abdomen impedance (magnitude of Zd-a). Unilateral and bilateral leg lifts, in addition to increasing magnitude of Zd-a, increased magnitude of Zrc. Passive 90 degrees rotation of the torso caused approximately 25% increases in magnitude of Zrc and magnitude of Zd-a; if the rotation was actively maintained by the trunk muscles, both regional impedances increased over 100%. Increases in magnitude of regional impedance were correlated to increases in regional electromyographic activity; changes in phase were small. Passive restriction of rib cage displacement by strapping increased magnitude of Zrc and magnitude of Zw but not magnitude of Zd-a, whereas abdominal strapping increased magnitude of Zd-a but did not affect magnitude of Zrc or magnitude of Zw.(ABSTRACT TRUNCATED AT 250 WORDS)

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