The effects of inhibition of plasma cholinesterase activity on systemic toxicity and blood catecholamine levels from cocaine infusion in pigs

We Investigated systemic effects and possible mechanisms tor lethality of intravenously infused cocaine in spontaneously breathing and mechanically ventilated unconscious Landrace male pigs weighing about 26 kg (25.75 ± 0.25 kg) that were pretreated with either saline solution (groups 1 and 3) or iso-ompa (tetraisopropyl pyrophosphoramide), a specific plasma cholinesterase inhibitor (groups 2 and 4). Pigs were made unconscious with sodium thiopental and ventilated with 70% nitrous oxide and 30% oxygen. A carotid arterial cannula and a Swan-Ganz catheter were inserted for hemodynamlc monitoring. Pigs in groups 1 and 2 were then allowed to breathe spontaneously and groups 3 and 4 were mechanically ventilated. After obtaining a stable state, as judged by cardiovascular and respiratory parameters, the pigs were infused Intravenously with cocaine hydrochloride (0.8 mg/kg/min) until the time of cardiac arrest. Respiratory and cardiovascular parameters, blood temperature, and sodium and potassium levels were monitored. The times of occurrence of respiratory arrests (RA), cardiac arrests (CA), and convulsions were recorded. Our results showed that RA is the primary cause of death in spontaneously breathing pigs and that mechanical ventilation significantly delayed the occurrence of CA (p < 0.05). Significant decreases in cardiac output, mean blood pressure, and heart rate as well as significant Increases in systemic and pulmonary vascular resistances, central venous and pulmonary wedge pressures, and blood K⁺ levels were noted in mechanically ventilated pigs (p < 0.05). Variable hemodynamic responses were noticed in spontaneously breathing pigs. Our results also showed that no significant changes occurred in blood catecholamine levels when compared with baseline values associated with the infusion of toxic closes of cocaine. Convulsions occurred only in the saline pretreated and mechanically ventilated group (group 3) of pigs. Our experiments demonstrated that pretreatment of pigs with either saline solution or iso-ompa resulted in a similar pattern of cardiovascular and respiratory systemic effects with continuous administration of Intravenous toxic doses of cocaine.